Abstract
Lifestyle, dietary, and nutritional choices are important influencing parameters of cardiovascular disease (CVD) risk, the number one cause of morbidity and mortality globally. Our aims were to i) characterize CVD risk parameters using data from 7939 participants enrolled in a preventive health and wellness program between March 2010 and January 2017; and ii) evaluate intervention effects in 3,020 participants who returned for follow-up. Blood measurements (nutrient markers), CVD risk parameters (abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein (HDL), insulin resistance, and inflammation), glycemic status (HbA1c), and insulin resistance (HOMA-IR) were assessed. Framingham and Reynold’s risk scores were also calculated. After approximately one year of treatment (n = 3 020), mean arachidonic acid:eicosapentaenoic acid (AA:EPA) ratio, homocysteine, and HbAlc concentrations were significantly reduced; other risk parameters did not improve but mean values remained within reference ranges. Excluding participants taking related medications, 38.8%, 37.2%, 38.0%, 42.5%, and 59.7% of those with hyperglycemia, hypertriglyceridemia, low HDL, insulin resistance, or prediabetes, respectively, at baseline no longer had the condition at follow-up. In contrast, of individuals within the reference range at baseline, new cases at follow-up were found for 10.1%, 12.2%, 6.3%, 8.2%, and 7.6% (as above, respectively). Regression models revealed a significant association between serum 25-hydroxyvitamin D concentrations ≥100 nmol/L and reductions in many CVD risk parameters after adjustment for confounding variables. These findings suggest that a preventive approach to health and wellness focused on nutrients, optimal serum 25-hydroxyvitamin D concentrations, and lifestyle changes has the potential to reduce the risk of CVD.
Introduction
Cardiovascular disease (CVD), which includes heart disease and stroke, is the number one cause of death globally, killing 17.7 billion people each year and causing 31% of all deaths.1 In Canada, over 2 million people are living with CVD2 and the cost to the Canadian economy exceeds $20 billion annually.3 To improve the cardiovascular health of Canadians, the Heart and Stroke Foundation of Canada announced two goals in 2014: (1) reduce the prevalence of cardiovascular risk parameters by 10%, and (2) reduce cardiovascular deaths in Canada by 25%, both by the year 2020.4 Community based health and wellness programs are attractive options to achieve these goals since these programs target all groups in the community and can achieve widespread risk reduction.
The Pure North S’Energy Foundation (Pure North) provides a preventative health and wellness program to western Canadians to address common health challenges and chronic illnesses, including CVD. This program offers participants personalized health assessments, nutritional supplements, and lifestyle counselling. Recommendations are made to improve diet and increase physical activity with specific advice tailored to the individual’s needs and abilities. A core goal of the program is to achieve physiological or “optimal” vitamin D levels, defined as serum 25-hydroxyvitamin D [25(OH)D] concentrations >100 nmol/L.5 Vitamin D deficiency has been linked to the vast majority of CVD risk parameters, including abdominal obesity, hypertension, hyperglycemia, hyperlipidemia, and inflammation.6-8 Moreover, one-third of Canadians are vitamin D deficient, defined by 25(OH)D concentrations <50 nmol/L9, and do not consume enough vitamin D to meet the Recommended Daily Allowance.10 In contrast, 12% of Canadians have a serum 25(OH)D concentration >100 nmol/L.11
Vitamin D may reduce CVD risk parameters through down regulation of the renin-angiotensin-aldosterone system, lowering homocysteine concentrations, decreasing inflammation, and mechanisms involving vascular endothelial function.12 Similarly, many of the other vitamins and nutrients provided as part of the Pure North programs are involved in distinct pathways that contribute to CVD risk parameters. Vitamins B12 (methylcobalamin), B9 (folate), and B6 can help lower homocysteine concentrations.13 Magnesium plays a critical role in modulating endothelial cell function and vascular smooth muscle tone.14 High intakes of omega-3 fatty acids have cardioprotective effects, including anti-atherogenic, anti-thrombogenic, anti-inflammatory, and anti-oxidant properties.15 Docosahexaenoic acid and eicosapentaenoic acid have recently been shown to attenuate stress-induced damage to the vasculature.16 Antioxidants from food sources have consistently been found to have a protective effect against CVD.17 Together, lifestyle advice and nutrient supplements may reduce the risk of CVD.
Evidence on the effectiveness of community-based health and wellness programs is essential to identify meaningful CVD risk and disease reduction strategies that are scalable and to avoid the waste of scarce financial resources. Our interest was to evaluate the effect of participation in the Pure North program on CVD risk parameters including abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, inflammation, glycemic status, and insulin resistance. We also assessed Framingham and Reynold’s risk scores.
Methods
Study Design and Dataset Construction
This was a retrospective database analysis and secondary use of data collected from participants in the Pure North program who began treatment between January 1, 2010 and December 31, 2016 and who met the inclusion criteria for the dataset. This study was approved by the research ethics board at St. Mary’s University, Calgary, Alberta (#067FA2017). Participants provided written informed consent for the secondary use of their data for research.
The dataset was constructed using anonymized information for males ≥45 years and females ≥55 years18 with the following information and measurements recorded: body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), 25(OH)D, high-sensitivity C reactive protein (hs-CRP), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting triglycerides (TG), fasting blood glucose (FBG) (≥8 hours), fasting insulin (≥8 hours), glycosylated hemoglobin (HbAlc), and history of tobacco use. Additional measures were included in the dataset when available for participants.
To begin our assessment, we first performed a cross-sectional analysis at baseline and subsequently analyzed longitudinal data to characterize CVD risk parameters over time.
The Pure North S’Energy Foundation Program
Pure North is a not-for-profit organization based in Calgary, Alberta, that focuses on the prevention of chronic disease. Although only participants who met our inclusion criteria were included in the dataset for this study, there is no inclusion/exclusion criteria for entering the program. Following entry, each participant met with a health care professional (Medical Doctor, Nurse Practitioner, and/or Naturopathic Doctor) who provided lifestyle advice appropriate for the individual’s health goals and current diagnoses. Dietary advice was provided as deemed appropriate, such as the DASH diet for hypertensive participants, with a general focus on increasing vegetable and fruit intake, reducing processed foods, and avoiding added sugars. Nutritional supplements were provided as required to address common nutrient deficiences such as magnesium, vitamin B12, and vitamin D deficiency. Smoking cessation advice was provided, and exercise deemed appropriate for the participant’s current health status was recommended.
Program Procedures and Data Collection
Participants were interviewed and assessed by health care professionals at each program visit to collect demographic information, medical history, medication use (including blood pressure-lowering and anti-hyperglycemic medications), and blood work. Visits occured every six to 12 months. Dataset parameters included available measurements for the first encounter and the date closest to 12 months of follow-up.
Participants were asked about their alcohol consumption, tobacco use, and typical levels of physical activity. Fruit, vegetable, and fish consumption were recorded as the number of servings consumed per day or week.
Body measurements included weight, in light clothing (to nearest 0.1 kg), and height (to nearest 0.5 cm), measured twice. BMI was calculated from the average weight (kg) divided by the average height (m) measurement squared. Systolic and diastolic blood pressure were measured by a trained nurse using a mercury sphygmomanometer (Welch Allyn, Germany), with an accuracy of 2 mmHg, with an appropriate cuff (Adult 11, 25-34 cm) on the dominant arm in the sitting position in a quiet room after a five minute rest.
Biochemical assessment of blood markers was performed by Doctor’s Data (St. Charles, Illinois) and Calgary Laboratory Services (Calgary, Alberta). Both are fully accredited laboratories by Clinical Laboratory Improvement Amendments. The methods for biochemical assessment from each lab and the CVs of each assay are published elsewhere.19,20
Intervention Supplements
The Vital 2 Platinum multivitamin/multimineral formulation (Supplementary Table S1) was introduced in 2010 and a number of other supplements were incorporated with it and later packaged in easy-to-open daily packets called “Vitality Packs.” The supplements provided were sourced from Bioclinic Naturals (Coquitlam, British Columbia) and include V2P, omega-3 fatty acids [OptiMega-3 (400 mg EPA and 200 mg DHA) ], and vitamin B12 (500 mcg methylcobalamin). A bottle of vitamin D3 (1000 IU/drop) was provided. Additional high-quality supplements were provided on a discretionary basis, typically in response to deficiency or clinical indication, including vitamin C (1000 mg), Magnesium CitraMal (150 mg magnesium citrate, malate) and Probiotic-Pro12 from Bioclinic Naturals, and Bone Renewal and Cell Protector from Synergy Company (Moab, Utah).
Supplemental Table S1.
Formulation of Vital 2 Platinum multivitamin.
| Ingredients | |
|---|---|
| Vitamin C (ascorbic acid) | 167 mg |
| Thiamine (HCl) | N/A |
| Vitamin B2 (riboflavin) | 4.2 mg |
| Niacin | 12.5 mg |
| Vitamin B6 (pyridoxine HCl) | 2.5 mg |
| Folic Acid (folate) | 83 mcg |
| Vitamin B12 (cyanocobalamin) | 167 mcg |
| Biotin | 8.3 mcg |
| Pantothenic Acid (calcium-d-pantothenate) | 16.7 mg |
| Choline (bitartrate) | 4.2 mg |
| Inositol | 4.2 mg |
| Para-Aminobenzoic Acid | 4.2 mg |
| Niacinamide | 33.3 mg |
| Selenium (selenomethionine) | 33.3 meg |
| Zinc (citrate) | 2.5 mg |
| Vitamin E (d-alpha tocopheryl acetate) | N/A |
| Chromium (chelate) | N/A |
| Vitamin D (cholecalciferol) | N/A |
| Vitamin A Palmitate | 150 mcg RAE (500 IU) |
| Vitamin B1 (Thiamine HCl) | 4.2 mg |
| Vitamin D3 (Cholecalciferol) | 8.3 mcg (333 IU) |
| Gamma Tocopherol | 33.3 mg |
| Vitamin K2 (Menaquinone 7) | 7.5 mcg |
| Calcium (HVP*Chelate) | 16.7 mg |
| Magnesium (HVP*Chelate) | 33.3 mg |
| Potassium (Citrate) | 6.8 mg |
| Manganese (Citrate) | 0.8 mg |
| Copper (HVP*Chelate) | 0.17 mg |
| Iodine (Ascophyllum nodosum) (whole plant) | 0.17 mg |
| Chromium (Chromium Polynicotinate) | 33.3 mcg |
| Molybdenum (Citrate) | 66.7 mcg |
| Vanadium (Citrate) | 2.5 mcg |
| Boron (Citrate) | 41.7 mcg |
| Betaine (Betaine HCL) | 16.7 mg |
| Citrus Bioflavonoids (Citrus limonum, Citrus sinensis) (fruit) 4:1 Extract | 8.3 mg |
| Hesperidin (Citrus sinensis) (fruit) | 4.2 mg |
| R-Alpha-Lipoic Acid | 41.7 mg |
| N-Acetyl Cysteine | 25 mg |
| Co enzyme Q10 (microorganism) | 8.3 mg |
| ResveratrolRich™ Proprietary Blend Wine Grape (Vitis vinifera) powdered extract (fruit) and Japanese knotweed (Polygonum cuspidatum) (root) | 16.7 mg |
| Lutein (Tagetes erecta) (flower) (10% lutein) | 0.55 mg |
| LYC-O-MATO® Lycopene (Lycopersicon esculentum) (5% Lycopene) | 275 mcg |
| Bilberry extract (Vaccinium myrtillus) (fruit) (25% Anthocyanidins) | 6.7 mg |
| Green Tea Phytosome® (Camellia sinensis) (leaf) (13% EPGC) | 8.3 mg |
| Milk Thistle Phytosome® (Silybum marianum) (seed) (15% Silybin) | 25 mg |
Non-medicinal Ingredients: Microcrystalline cellulose, croscarmellose sodium, coating (methylcellulose, glycerin), vegetable grade magnesium stearate (lubricant)
All participants are encouraged to reach physiological serum 25(OH)D concentrations of 100-250 nmol/L, levels that can be naturally attained through regular sun exposure containing UVB rays, without the use of sunscreen.19 Because of the substantial inter-individual differences in response to a given dose of vitamin D3, dosages were adjusted accordingly for the individuals to achieve the target serum 25(OH)D levels. Vitamin D3 doses were often above 4000 IU/d, and safely ranged from 1000 to 20 000 IU/d under medical supervision.21
Dataset Definitions
Based on the Endocrine Society’s guidelines, vitamin D deficiency was defined as serum 25(OH)D <50 nmol/L22 and was considered a CVD risk parameter. Optimal vitamin B12 was defined as ≥450 pmol/L23 and <148 pmol/L as deficient. Overweight and obesity were defined as BMI of 25 to 29.9 and ≥ 30 kg/m2, respectively.
CVD risk parameters included abdominal obesity [waist circumference (WC) ≥102 cm for men, WC ≥88 cm for women], hypertension [SBP ≥130 and DBP ≥85 mmHg],24 hypertriglyceridemia [fasting triglycerides (TG) ≥ 1.7 mmol/L], high LDL (>3.0 mmol), and hyperglycemia (FBG ≥5.6 mmol/L). Metabolic syndrome was diagnosed in participants with three or more of the five CVD risk parameters.25 Low HDL (<1.03 mmol in men, <1.3 mmol/L in women) was also considered a risk factor for CVD.
Patient history of CVD included previous myocardial infarction, transient ischemic attack and stroke, documented coronary artery disease including elevated coronary calcium score, coronary artery bypass surgery and/or stent, congestive heart failure, atherosclerosis, and peripheral vascular disease. Cardiac medications included angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), cardiac glucoside, loop diuretics, nitrate vasodilators, potassium-sparing diuretics and thiazide diuretics. Hypertension medications included calcium channel blockers, renin inhibitors, ARB with thiazides, and beta-blockers. Diabetes medications included alpha-glucosidase inhibitors, amylin analogs, dipeptidyl peptidase 4 inhibitors, incretin mimetics, insulin, meglitinic, non-sulfonylureas, prolactin inhibitors, SGLT-2 inhibitors, sulfonylureas, and thiazolidinediones.
According to Kamath et al.26, serum hs-CRP concentrations >3 mg/L are considered high risk for CVD and concentrations between 1 and 3 mg/L are an intermediate risk; we considered participants with serum hs-CRP concentrations >2 mg/L at risk. Homocysteine concentrations ≥12 were considered high risk with 8-12 μmol/L considered low risk.27 The arachidonic acid to eicosapentaenoic acid (AA:EPA) ratio and oxidized LDL (Ox-LDL) levels were evaluated as markers of inflammation.
Categorical glycemic status was defined according to HbA1c values with normoglycemia <5.8%, prediabetes 5.8-6.4%, and type 2 diabetes >6.4%.28,29 Prediabetic participants were considered at risk for developing diabetes.
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated as: [ (fasting blood glucose (mmol/L) × fasting insulin (μU/mL) ) /22.5]. Insulin resistance (HOMA IR≥2.73) was considered a CVD risk parameter. Framingham risk score was used to estimate the 10-year cardiovascular disease risk with ≥20% and 10-<20% considered as high and intermediate risk levels, respectively.30 Ten-year CVD risk was calculated using Reynold’s risk scores, a modified Framingham risk score that includes family history and hs-CRP.
Statistical Analyses
All statistical analyses were performed using SPSS version 23 (SPSS Inc., Chicago, Illinois). Descriptive analyses were performed for distribution of data and to determine incidence for categorical variables. The normality of data was tested using histograms and the Kolmogorov-Smirnov test. Paired t-tests were performed to evaluate changes within groups in biometrics and biomarkers over time. Pearson correlations were used to determine the relationship between nutrient levels measured (including serum 25(OH)D, vitamin B12, and AA:EPA ratio) at follow-up and different CVD risk parameters. One-way ANOVA tests were performed to compare different parameters according to nutrient levels at baseline. Chi-square tests were performed to determine the association between CVD risk parameters and nutrient levels. Relative risks were calculated by comparing CVD risk parameters with 25(OH)D status. General Linear Models (univariate analyses) were conducted for confounding parameters with each CVD risk parameter. The probable confounding parameters in these analyses were: age, gender, serum 25(OH)D, serum vitamin B12, BMI, fruit and vegetable consumption, fish consumption, AA:EPA, alcohol consumption, tobacco use, exercise, past medical history, and medication use. Baseline serum 25(OH)D concentrations were categorized as the following: <50, 50-<75, 75-<100, and ≥100 nmol/L. The group with the lowest concentration of serum 25(OH)D (<50 nmol/L) was considered the reference group. Binary logistic regressions (multivariable analyses) were performed to evaluate the association between serum 25(OH)D concentration and CVD risk with all covariates added that were significant in univariate models. Significance level was defined as P<.05.
Results
Of the 32730 participants whose data were available, 7 939 met the inclusion criteria at entry to program (baseline) and were included in the baseline assessment of this study. Of these, follow-up data (average 366 ± 78 days after the initial visit) was available for 3 020 participants. A flow diagram demonstrating the criteria for participant inclusion is shown in Figure 1.
Figure 1.
Flow of Participants Included in Dataset
Cross Sectional Analysis
Participant demographics, body composition, and the prevalence of CVD risk parameters at baseline are presented in Table 1. Mean age was 60.2 ± 9.0 years and 43.4% were female. BMI classifications compare closely with the general Canadian population,31 with 38.9% overweight and 32.4% obese. Vitamin D deficiency (25(OH)D <50 nmol/L) was observed in 48.2% and 24.1% were optimal (≥100 nmol/L) at baseline. 37.2% had optimal vitamin B12 levels. Because the focus of the program is on achieving optimal 25(OH)D levels, we further characterized baseline measures by 25(OH)D range (Table 1). Blood pressure, inflammation markers (hs-CRP, homocysteine, and AA:EPA), lipid levels (TG, LDL, Ox-LDL) and glycemic status (FPG, insulin, HOMA-IR and HbA1c) were significantly inversely associated with serum 25(OH)D concentrations. HDL was significantly positively associated with serum 25(OH)D. Of note, the difference in mean HOMA-IR and HbA1c was the difference between being classified as insulin resistant and diabetic in the lowest 25(OH)D range (0-<50 nmol/L) versus the highest 25(OH)D range (≥100 nmol/L). Increased serum 25(OH)D concentrations were significantly associated with lower mean Framingham and Reynold’s risk scores. There was no association between 25(OH)D and physical activity level or markers of healthier dietary patterns (greater fruit, vegetable and fish consumption).
Table 1.
Baseline characteristics of all participants and all participants in accordance to serum 25(OH)D status.
| Serum 25(OH)D categories (nmol/L) | |||||
|---|---|---|---|---|---|
| All | 0 to <50 | 50 to <75 | 75 to <100 | ≥100 | |
| Number of participants | 7939 | 1,296 | 2533 | 2198 | 1912 |
| Age (year), mean (SD) | 60.2 ± 9.0 | 56.9 ± 8.4d | 59.5 ± 8.7c | 61.5 ± 9.0b | 62.2 ± 8.9a |
| Gender, n (%) e | |||||
| Female | 3443 (43.4) | 353 (27.2) | 949 (37.5) | 1070 (48.7) | 1071 (56.0) |
| Male | 4496 (56.6) | 943 (72.8) | 1584 (62.5) | 1128 (51.3) | 841 (44.0) |
| Ethnicitye | |||||
| North American | 5164 (82.2) | 646 (72.3) | 1648 (82.5) | 1514 (84.2) | 1356 (84.9) |
| Aboriginal | 334 (5.3) | 111 (12.4) | 120 (6.0) | 61 (3.4) | 42 (2.6) |
| Asian | 331 (5.3) | 64 (7.2) | 107 (5.4) | 89 (5.0) | 71 (4.4) |
| European | 326 (5.2) | 23 (2.6) | 78 (3.9) | 103 (5.7) | 122 (7.7) |
| African/Latin American | 131 (2.1) | 49 (5.5) | 45 (2.2) | 30 (1.7) | 7 (0.4) |
| BMI (kg/m2) | 28.3 ± 5.5 | 29.6 ± 6.1a | 29.4 ± 5.6a | 27.9 ± 5.1b | 26.6 ± 4.7c |
| BMI category, n (%) e | |||||
| Underweight | 66 (0.8) | 10 (0.8) | 14 (0.5) | 17 (0.8) | 25 (1.3) |
| Normal weight | 2211 (27.9) | 285 (22.0) | 500 (19.8) | 662 (30.1) | 764 (40.0) |
| Overweight | 3084 (38.9) | 454 (35.1) | 1018 (40.3) | 890 (40.5) | 722 (37.8) |
| Obese | 2568 (32.4) | 546 (42.1) | 997 (39.4) | 627 (28.6) | 398 (20.9) |
| Ethnic-based obesity, n (%) e | 2142 (34.1) | 413 (46.2) | 844 (42.2) | 551 (30.7) | 334 (20.9) |
| Abdominal obesity, n (%) * | 3722 (47.3) | 713 (55.4) | 1,353 (54.0) | 974 (44.8) | 682 (35.9) |
| Ethnic-based abdominal obesity, n (%) e | 2200 (35.3) | 449 (50.6) | 872 (44.0) | 552 (31.0) | 327 (20.6) |
| WC (cm) | 96.3 ± 14.6 | 101.3 ± 15.0a | 99.3 ± 13.9b | 94.7 ± 13.9c | 90.9 ± 13.7d |
| SBP (mmHg) | 128.1 ± 16.9 | 128.9 ± 16.5ab | 129.4 ± 16.9a | 127.6 ± 16.7bc | 126.6 ± 17.2c |
| DBP (mmHg) | 79.5 ± 9.9 | 80.9 ± 9.8a | 80.3 ± 9.9b | 78.9 ± 9.6b | 77.9 ± 9.8c |
| Hypertension, n (%) e | 2535 (31.9) | 514 (39.7) | 887 (35.0) | 639 (29.1) | 495 (25.9) |
| 25(OH)D (nmol/L) | 81 ± 35 | 38 ± 8d | 63 ± 7c | 86 ± 7b | 129 ± 31a |
| Calcium (mmol/L) | 2.37 ± 0.11 | 2.36 ± 0.11b | 2.36 ± 0.10b | 2.37 ± 0.10a | 2.38 ± 0.11a |
| Mean AA:EPA ratio | 16.1 ± 7.6 | 20.4 ± 6.8a | 17.3 ± 7.0b | 15.3 ± 7.4c | 12.9 ± 7.2d |
| Vitamin B12 (pmol/L) | 458 ± 299 | 334 ± 195d | 392 ± 244c | 484 ± 290b | 600 ± 363a |
| Homocysteine (μmol/L) e | 10.8 ± 3.0 | 11.6 ± 3.4a | 11.0 ± 3.0b | 10.6 ± 3.0c | 10.1 ± 2.8d |
| Normal, n (%) | 1168 (14.9) | 108 (8.4) | 299 (11.9) | 353 (16.3) | 408 (21.6) |
| Low, n (%) | 4495 (57.3) | 686 (53.6) | 1438 (57.4) | 1,283 (59.0) | 1,088 (57.5) |
| High, n (%) | 2187 (27.9) | 486 (38.0) | 768 (30.7) | 537 (24.7) | 396 (20.9) |
| hs-CRP (mg/L) e | 2.48 ± 3.1 | 2.91 ± 3.3a | 2.64 ± 3.2b | 2.37 ± 3.1c | 2.11 ± 2.8c |
| Low, n (%) | 2922 (36.8) | 384 (29.6) | 836 (33.0) | 879 (40.0) | 823 (43.0) |
| Intermediate, n (%) | 3116 (39.3) | 516 (39.8) | 1054 (41.6) | 813 (37.0) | 733 (38.4) |
| High, n (%) | 1898 (23.9) | 396 (30.6) | 642 (25.4) | 504 (23.0) | 356 (18.6) |
| Inflammation (hs-CRP≥2 mg/L) e | 3007 (37.8) | 599 (46.2) | 1033 (40.8) | 773 (35.2) | 602 (31.5) |
| Total cholesterol (mmol/L) | 5.13 ± 1.0 | 5.12 ± 1.1 | 5.15 ± 1.0 | 5.15 ± 1.0 | 5.10 ± 1.0 |
| TG (mmol/L) | 1.36 ± 0.7 | 1.57 ± 0.8a | 1.46 ± 0.7b | 1.30 ± 0.6c | 1.14 ± 0.6d |
| Hypertriglyceridemia, n (%) e | 1,915 (24.1) | 453 (35.0) | 733 (28.9) | 473 (21.5) | 256 (13.4) |
| HDL (mmol/L) | 1.48 ± 0.4 | 1.34 ± 0.4d | 1.41 ± 0.4c | 1.53 ± 0.4b | 1.62 ± 0.5a |
| Low HDL, n (%) e | 1495 (18.8) | 347 (26.8) | 514 (20.3) | 384 (17.5) | 250 (13.1) |
| LDL (mmol/L) e | 3.04 ± 0.9 | 3.08 ± 0.9a | 3.09 ± 0.9a | 3.05 ± 0.9a | 2.97 ± 0.9b |
| High LDL, n (%) | 2370 (29.9) | 424 (32.7) | 771 (30.4) | 663 (30.2) | 512 (26.8) |
| Ox-LDL (U/L) | 48.1 ± 13.7 | 49.8 ± 14.6a | 49.0 ± 13.6ab | 47.9 ± 13.4b | 46.1 ± 13.4c |
| HbA1c, (%) e | 5.83 ± 0.7 | 6.00 ± 1.0a | 5.86 ± 0.8b | 5.79 ± 0.7b | 5.72 ± 0.5b |
| Prediabetes, n (%) | 2549 (32.1) | 462 (35.9) | 824 (32.8) | 675 (30.8) | 588 (30.9) |
| Diabetes, n (%) | 759 (9.6) | 191 (14.9) | 270 (10.8) | 187 (8.5) | 111 (5.8) |
| FBG (mmol/L) | 5.22 ± 1.5 | 5.46 ± 2.0a | 5.30 ± 1.6b | 5.14 ± 1.3c | 5.02 ± 1.1c |
| Elevated FBG, n (%) e | 1414 (18.0) | 322 (25.1) | 522 (20.8) | 335 (15.4) | 235 (12.4) |
| Fasting insulin (pmol/L) | 62.7 ± 48.3 | 75.6 ± 59.3a | 66.8 ± 52.4b | 58.4 ± 42.1c | 53.2 ± 36.9d |
| HOMA-IR* | 2.78 ± 15.0 | 4.09 ± 24.5a | 2.66 ± 7.5b | 2.20 ± 4.8b | 2.72 ± 20.6b |
| Insulin resistance (≥2.73), n (%) | 1605 (20.5) | 387 (30.2) | 596 (23.8) | 381 (17.5) | 241 (12.8) |
| Metabolic syndrome, n (%) e | 1357 (17.1) | 346 (26.7) | 525 (20.7) | 311 (14.1) | 175 (9.2) |
| Mean Framingham risk score, n (%) e | 13.3 ± 8.5 | 15.1 ± 8.6a | 14.1 ± 8.5b | 12.8 ± 8.4c | 11.5 ± 8.2d |
| Low | 3560 (44.8) | 449 (34.6) | 1,028 (40.6) | 1,042 (47.4) | 1,041 (54.4) |
| Intermediate | 2600 (32.8) | 474 (36.6) | 877 (34.6) | 701 (31.9) | 548 (28.7) |
| High | 1779 (22.4) | 373 (28.8) | 628 (24.8) | 455 (20.7) | 323 (16.9) |
| Mean Reynold’s risk score (%) | 6.8 ± 7.2 | 7.1 ± 6.7a | 7.2 ± 7.1a | 6.8 ± 7.7a | 6.1 ± 7.0b |
| High Reynold’s risk score (>10%) | 1473 (19.4) | 248 (20.4) | 512 (21.1) | 386 (18.3) | 327 (17.8) |
| Self-reported medical history, n (%) | |||||
| Hypertensionf | 1193 (25.2) | 177 (26.1) | 398 (26.0) | 357 (25.6) | 261 (22.9) |
| Heart diseasef | 333 (7.0) | 39 (5.8) | 119 (7.8) | 84 (6.0) | 91 (8.0) |
| Diabetes e,f | 489 (10.3) | 105 (15.5) | 172 (11.3) | 130 (9.3) | 82 (7.2) |
| Self-reported medication history, n (%) | |||||
| Blood pressure-lowering med.* | 1169 (35.1) | 142 (31.8) | 398 (36.8) | 381 (38.0) | 248 (31.2) |
| Cardiac med. | 993 (29.9) | 124 (27.7) | 333 (30.8) | 323 (32.2) | 213 (26.8) |
| Diabetic med.e | 404 (12.1) | 95 (21.3) | 136 (12.6) | 105 (10.5) | 68 (8.6) |
| Use tobacco, n (%) * | 1933 (25.0) | 509 (41.3) | 656 (26.6) | 447 (20.8) | 321 (17.2) |
| Alcohol consumptione,f n (%) | 5824 (73.4) | 884 (68.2) | 1813 (71.6) | 1665 (75.8) | 1462 (76.5) |
| Physical activity, n (%) e | |||||
| None | 320 (18.6) | 69 (28.0) | 124 (19.8) | 88 (17.5) | 39 (11.3) |
| Mild | 911 (53.0) | 126 (51.2) | 339 (54.1) | 257 (51.2) | 189 (54.8) |
| Moderate | 429 (24.9) | 41 (16.7) | 153 (24.4) | 136 (27.1) | 99 (28.7) |
| Strenuous | 60 (3.5) | 10 (4.1) | 11 (1.7) | 21 (4.2) | 18 (5.2) |
| Fruit consumption, n (%) e | |||||
| None | 242 (4.5) | 58 (8.2) | 89 (5.2) | 59 (3.7) | 36 (2.7) |
| 1-2 servings/day | 2,740 (51.1) | 414 (58.6) | 898 (52.7) | 795 (49.8) | 633 (46.5) |
| 3-4 servings/day | 1880 (35.0) | 184 (26.0) | 581 (34.1) | 595 (37.3) | 520 (38.2) |
| 5 & over servings/day | 505 (9.4) | 51 (7.2) | 135 (7.9) | 148 (9.3) | 171 (12.6) |
| Vegetable consumption, n (%) e | |||||
| None | 82 (1.5) | 19 (2.7) | 28 (1.6) | 25 (1.6) | 10 (0.7) |
| 1-2 servings/day | 2336 (43.5) | 384 (54.1) | 794 (46.6) | 651 (40.8) | 507 (37.2) |
| 3-4 servings/day | 2112 (39.3) | 231 (32.5) | 648 (38.1) | 658 (41.2) | 575 (42.2) |
| 5 & over servings/day | 842 (15.7) | 76 (10.7) | 233 (13.7) | 261 (16.4) | 272 (19.9) |
| Fish consumption, n (%) e | |||||
| None | 674 (14.6) | 135 (21.2) | 233 (16.4) | 168 (12.3) | 138 (11.6) |
| 1 serving/week | 1068 (23.1) | 156 (24.4) | 314 (22.1) | 331 (24.1) | 267 (22.5) |
| 2 servings/week | 1399 (30.3) | 169 (26.5) | 415 (29.2) | 429 (31.3) | 386 (32.4) |
| 3 & more servings/week | 1477 (32.0) | 178 (27.9) | 458 (32.3) | 443 (32.3) | 398 (33.5) |
a-dMeans in a row without common superscript letters are significantly different (P < .05), as analyzed by one-way ANOVA
eAssociation with serum 25(OH)D level was significant (P<.05)
fPercentages for variables that do not include missing observations
Abbreviations: AA, arachidonic acid; BMI, body mass index; DBP, diastolic blood pressure; EPA, eicosapentaenoic acid; FBG, fasting blood glucose; HDL, high-density lipoproteins; hs-CRP, high sensitivity C-reactive protein; LDL, low-density lipoproteins; Ox-LDL, Oxidized LDL; SBP, systolic blood pressure; SD, standard deviation; TG, fasting triglycerides, WC, waist circumference
The prevalence of CVD risk parameters among the participants was quite high: 47.3% had abdominal obesity, 31.9% hypertension, 24.1% hypertriglyceridemia, 18.8% low high-density lipoprotein (HDL) levels, and 18.0% were hyperglycemic (Table 1). Over 41% of the participants were prediabetic or diabetic and 20.5% were insulin resistant. An additional 17.1% were classified as having metabolic syndrome. Framingham risk scores were considered high (≥20%) in 22.4% of the participants and 22.6% of participants had high Reynold’s risk scores (≥10%). Tobacco use was reported by 25.5%, alcohol consumption by 73.4%, and no physical activity by 18.6%. Only 9.4% and 15.7% consumed five or more servings of fruit and vegetables each day, respectively. Three or more servings of fish each week were consumed by 32% of the participants.
Retrospective Analysis of Follow-up
We investigated changes in the demographics, body composition, and the prevalence of CVD risk parameters for 3 020 participants with data recorded at baseline and at follow-up, roughly one year after entry (Table 2); information of these participants according to serum 25(OH)D categories are provided in Supplementary Table S2. There was no significant change in mean BMI or WC between baseline and follow-up. Mean serum 25(OH)D increased from 91 to 116 nmol/L (P <.01) and the prevalence of vitamin D deficiency (<50 nmol/L) decreased from 20% at baseline to 2% at follow-up; 60% of participants achieved optimal 25(OH)D concentrations (>100 nmol/L) at follow-up. Mean serum vitamin B12 also increased significantly from 510 ± 316 pmol/L to 1521 ± 1206 pmol/L, with achieved optimal vitamin B12 (>450 pmol/L) for 86% of participants. DBP, AA:EPA, homocysteine, and HbA1c were significantly decreased. In participants with baseline and follow-up measures, there were significant increases in mean SBP, TG, LDL, Ox-LDL, FBG, and both Framingham and Reynold’s risk scores, and significant decreases in HDL. The use of tobacco was significantly reduced at follow-up and participants reported higher intake of fruits, vegetables, and fish. Alcohol consumption was lower and participants were less physically active at follow-up.
Table 2.
Longitudinal comparison of mean measures of biometrics and biomarkers in participants with baseline and follow-up results which are taken approximately one year after baseline.
| Baseline | Year 1 | |||
|---|---|---|---|---|
| n | Mean ± SD | Mean ± SD | P Value | |
| BMI (kg/m2) | 2880 | 28.0 ± 5.1 | 28.1 ± 5.0 | .74 |
| WC (cm) | 3007 | 94.0 ± 14.3 | 93.8 ± 14.4 | .07 |
| SBP (mmHg) | 3020 | 126.8 ± 16.4 | 128.5 ± 17.3 | <.01 |
| DBP (mmHg) | 3020 | 78.8 ± 9.5 | 77.6 ± 9.5 | <.01 |
| 25(OH)D (nmol/L) | 3020 | 91 ± 37 | 116 ± 37 | <.01 |
| Calcium (albumin corrected) (mmol/L) | 2953 | 2.38 ± 0.1 | 2.35 ± 0.1 | <.01 |
| AA:EPA | 758 | 15.3 ± 7.3 | 8.7 ± 5.2 | <.01 |
| Vitamin B12 (pmol/L) | 2991 | 510 ± 316 | 1521 ± 1206 | <.01 |
| Homocysteine (μmol/L) | 1519 | 10.4 ± 2.6 | 8.6 ± 2.0 | <.01 |
| hs-CRP (mg/L) | 2989 | 2.13 ± 2.7 | 2.10 ± 2.7 | .62 |
| Total cholesterol (mmol/L) | 3009 | 5.21 ± 1.0 | 5.22 ± 1.0 | .66 |
| TG (mmol/L) | 3020 | 1.27 ± 0.6 | 1.36 ± 0.6 | <.01 |
| HDL (mmol/L) | 3020 | 1.57 ± 0.5 | 1.48 ± 0.4 | <.01 |
| LDL (mmol/L) | 3020 | 3.08 ± 0.9 | 3.19 ± 0.9 | <.01 |
| Ox-LDL (U/L) | 2983 | 48.0 ± 13.2 | 52.2 ± 14.3 | <.01 |
| HbA1c (%) | 3000 | 5.77 ± 0.5 | 5.63 ± 0.5 | <.01 |
| FBG (mmol/L) | 3001 | 5.04 ± 1.1 | 5.28 ± 0.8 | <.01 |
| Fasting insulin (pmol/L) | 2434 | 61.7 ± 41.0 | 60.4 ± 32.5 | .03 |
| HOMA-IR | 2997 | 2.67 ± 17.2 | 2.02 ± 2.5 | .02 |
| Framingham risk score (%) | 3009 | 12.3 ± 8.3 | 13.1 ± 8.6 | <.01 |
| Reynold’s risk score (%) | 2888 | 6.7 ± 7.2 | 6.9 ± 7.3 | <.01 |
| Currently smoking, n (%) | 2954 | <.01 | ||
| No | 2489 (84.3) | 2669 (90.4) | ||
| Yes | 465 (15.7) | 285 (9.7) | ||
| Alcohol drinking status, n (%) | 3019 | <.01 | ||
| Yes | 2350 (77.8) | 2150 (71.2) | ||
| No | 669 (22.2) | 869 (28.8) | ||
| Physical activity, n (%) | 248 | .02 | ||
| None | 20 (8.1) | 27 (10.9) | ||
| Mild | 139 (56.1) | 140 (56.5) | ||
| Moderate | 81 (32.7) | 76 (30.7) | ||
| Strenuous | 8 (3.2) | 5 (2.0) | ||
| Fruit consumption, n (%) | 2,130 | <.01 | ||
| None | 61 (2.9) | 33 (1.6) | ||
| 1-2 servings/day | 1,016 (47.7) | 940 (44.1) | ||
| 3-4 servings/day | 831 (39.0) | 872 (40.9) | ||
| 5 & more servings/day | 222 (10.4) | 285 (13.4) | ||
| Vegetable consumption, n (%) | 2,134 | <.01 | ||
| None | 18 (0.8) | 10 (0.4) | ||
| 1-2 servings/day | 789 (37.0) | 652 (30.6) | ||
| 3-4 servings/day | 920 (43.1) | 966 (45.3) | ||
| 5 & more servings/day | 407 (19.1) | 506 (23.7) | ||
| Fish consumption, n (%) | 1,513 | <.01 | ||
| None | 159 (10.5) | 141 (9.3) | ||
| 1 serving/week | 341 (22.5) | 359 (23.7) | ||
| 2 servings/week | 499 (33.0) | 477 (31.5) | ||
| 3 & more servings/week | 514 (34.0) | 536 (35.4) | ||
Abbreviations: AA, arachidonic acid; BMI, body mass index; DBP, diastolic blood pressure; EPA, eicosapentaenoic acid; FBG, fasting blood glucose; HDL, high-density lipoproteins; hs-CRP, high sensitivity C-reactive protein; LDL, low-density lipoproteins; Ox-LDL, Oxidized LDL; SBP, systolic blood pressure; SD, standard deviation; TG, fasting triglycerides, WC, waist circumference
Supplementary Table S2.
Baseline characteristics of participants with follow-up, aggregated and in accordance to serum 25(OH)D status.
| Serum 25(OH)D categories (nmol/L) | ||||||
|---|---|---|---|---|---|---|
| All | 0 to <50 | 50 to <75 | 75 to <100 | ≥100 | ||
| Number of participants | 3020 | 274 | 832 | 929 | 985 | |
| Age (year), mean (SD) | 62.6 ± 8.6 | 60.0 ± 8.9 | 63.2 ± 8.5 | 63.2 ± 8.5 | 63.5 ± 8.6 | |
| Gender, n (%) | ||||||
| Female | 1607 (53.2) | 106 (38.7) | 382 (45.9) | 519 (55.9) | 600 (60.9) | |
| Male | 1413 (46.8) | 168 (61.3) | 450 (54.1) | 410 (44.1) | 385 (39.1) | |
| Ethnicity | ||||||
| North American | 2410 (84.1) | 193 (75.7) | 667 (84.8) | 741 (84.0) | 809 (85.7) | |
| Aboriginal | 76 (2.6) | 20 (7.8) | 28 (3.6) | 15 (1.7) | 13 (1.4) | |
| Asian | 139 (4.9) | 20 (7.8) | 36 (4.6) | 44 (5.0) | 39 (4.4) | |
| European | 204 (7.1) | 14 (5.5) | 40 (5.1) | 70 (7.9) | 80 (7.7) | |
| African/Latin American | 38 (1.3) | 8 (3.2) | 15 (1.9) | 12 (1.4) | 3 (0.4) | |
| BMI (kg/m2) | 27.8 ± 5.3 | 29.9 ± 5.7 | 29.4 ± 5.6 | 27.5 ± 5.1 | 26.2 ± 4.5 | |
| BMI category, n (%) | ||||||
| Underweight | 21 (0.7) | 1 (0.4) | 4 (0.5) | 5 (0.5) | 11 (1.1) | |
| Normal weight | 952 (31.6) | 48 (17.6) | 156 (18.8) | 315 (34.0) | 433 (44.0) | |
| Overweight | 1168 (38.7) | 102 (37.3) | 343 (41.3) | 358 (38.6) | 365 (37.1) | |
| Obese | 873 (29.0) | 122 (44.7) | 327 (39.4) | 249 (26.9) | 175 (17.8) | |
| Ethnic-based obesity, n (%) | 880 (30.7) | 119 (46.7) | 332 (42.2) | 250 (28.3) | 179 (19.0) | |
| Abdominal obesity, n (%) | 1322 (44.0) | 154 (56.4) | 465 (56.2) | 381 (41.2) | 322 (32.8) | |
| Ethnic-based abdominal obesity, n (%) | 873 (30.6) | 119 (46.7) | 335 (42.8) | 245 (27.9) | 174 (18.5) | |
| WC (cm) | 94.0 ± 14.3 | 100.6 ± 14.3 | 98.8 ± 13.7 | 92.8 ± 13.7 | 89.2 ± 13.3 | |
| SBP (mmHg) | 126.8 ± 16.4 | 128.5 ± 16.4 | 129.2 ± 16.4 | 126.5 ± 15.5 | 124.6 ± 17.0 | |
| DBP (mmHg) | 78.8 ± 9.5 | 81.2 ± 9.3 | 80.3 ± 9.5 | 78.5 ± 9.0 | 77.3 ± 9.8 | |
| Hypertension, n (%) | 617 (27.8) | 79 (38.0) | 199 (32.9) | 175 (26.2) | 164 (22.2) | |
| 25(OH)D (nmol/L) | 91 ± 37 | 39 ± 9 | 64 ± 7 | 87 ± 7 | 131 ± 32 | |
| Calcium (mmol/L) | 2.38 ± 0.11 | 2.37 ± 0.11 | 2.37 ± 0.11 | 2.38 ± 0.11 | 2.39 ± 0.11 | |
| Mean AA:EPA ratio | 14.5 ± 7.2 | 19,2 ± 6.6 | 16.2 ± 6.8 | 14.1 ± 6.7 | 12.2 ± 7.2 | |
| Vitamin B12 (pmol/L) | 511 ± 318 | 336 ± 189 | 422 ± 263 | 522 ± 303 | 624 ± 357 | |
| Homocysteine (μmol/L) | 10.3 ± 2.8 | 11.4 ± 3.3 | 10.6 ± 2.6 | 10.2 ± 2.9 | 9.7 ± 2.6 | |
| Normal, n (%) | 571 (19.0) | 23 (8.4) | 123 (14.9) | 183 (19.8) | 242 (24.7) | |
| Low, n (%) | 1,748 (58.2) | 153 (56.0) | 487 (59.0) | 536 (58.0) | 572 (58.3) | |
| High, n (%) | 685 (22.8) | 97 (35.6) | 216 (26.1) | 205 (22.2) | 167 (17.0) | |
| hs-CRP (mg/L) | 2.15 ± 2.7 | 2.76 ± 3.3 | 2.28 ± 2.6 | 2.10 ± 2.7 | 1.93 ± 2.8 | |
| Low, n (%) | 1248 (41.3) | 85 (31.0) | 302 (36.3) | 402 (43.3) | 459 (46.6) | |
| Intermediate, n (%) | 1183 (39.2) | 112 (40.9) | 355 (42.7) | 342 (36.8) | 374 (38.0) | |
| High, n (%) | 589 (19.5) | 77 (28.1) | 175 (21.0) | 185 (19.9) | 152 (15.4) | |
| Inflammation (hs-CRP≥2 mg/L) | 987 (32.7) | 117 (42.7) | 309 (37.1) | 291 (31.3) | 270 (27.4) | |
| Total cholesterol (mmol/L) | 5.22 ± 1.0 | 5.30 ± 1.1 | 5.26 ± 1.0 | 5.23 ± 1.0 | 5.14 ± 1.0 | |
| TG (mmol/L) | 1.27 ± 0.6 | 1.58 ± 0.7 | 1.40 ± 0.7 | 1.25 ± 0.6 | 1.08 ± 0.5 | |
| Hypertriglyceridemia, n (%) | 588 (19.5) | 98 (35.8) | 216 (26.0) | 169 (18.2) | 105 (10.7) | |
| HDL (mmol/L) | 1.56 ± 0.5 | 1.36 ± 0.4 | 1.50 ± 0.4 | 1.58 ± 0.4 | 1.67 ± 0.5 | |
| Low HDL, n (%) | 1470 (15.6) | 78 (28.5) | 141 (17.0) | 137 (14.8) | 114 (11.6) | |
| LDL (mmol/L) | 3.08 ± 0.9 | 3.23 ± 0.9 | 3.14 ± 0.9 | 3.09 ± 0.9 | 2.98 ± 0.9 | |
| Oxidized LDL (U/L) | 48.0 ± 13.2 | 51.5 ± 14.3 | 48.7 ± 13.1 | 47.7 ± 13.0 | 46.7 ± 12.9 | |
| UbA1c, (%) | 5.83 ± 0.7 | 6.00 ± 1.0 | 5.86 ± 0.8 | 5.79 ± 0.7 | 5.72 ± 0.5 | |
| Prediabetes, n (%) | 2,549 (32.1) | 462 (35.9) | 824 (32.8) | 675 (30.8) | 588 (30.9) | |
| Diabetes, n (%) | 759 (9.6) | 191 (14.9) | 270 (10.8) | 187 (8.5) | 111 (5.8) | |
| FBG (mmol/L) | 5.04 ± 1.1 | 5.33 ± 1.5 | 5.13 ± 1.2 | 4.99 ± 0.9 | 4.93 ± 0.9 | |
| Hyperglycemia, n (%) | 428 (14.3) | 62 (22.8) | 146 (17.7) | 122 (13.2) | 98 (10.0) | |
| Fasting insulin (pmol/L) | 57.8 ± 41.2 | 70.5 ± 48.5 | 63.8 ± 46.8 | 56.5 ± 39.3 | 50.4 ± 32.9 | |
| HOMA-IR* | 2.67 ± 17.2 | 2.78 ± 5.7 | 2.77 ± 12.0 | 1.99 ± 3.8 | 3.21 ± 27.6 | |
| Insulin resistance (≥2.73), n (%) | 486 (16.2) | 73 (26.9) | 174 (21.1) | 132 (14.3) | 107 (11.0) | |
| Metabolic syndrome, n (%) | 403 (13.3) | 73 (26.6) | 148 (17.8) | 108 (11.6) | 74 (7.5) | |
| Mean Framingham risk score | 12.3 ± 8.3 | 14.5 ± 8.4 | 13.5 ± 8.4 | 12.1 ± 8.4 | 11.0 ± 8.0 | |
| Framingham risk score, n (%) | ||||||
| Low | 1481 (49.0) | 97 (35.4) | 357 (42.9) | 469 (50.5) | 558 (56.7) | |
| Intermediate | 953 (31.6) | 105 (38.3) | 286 (34.4) | 285 (30.7) | 277 (28.1) | |
| High | 586 (19.4) | 72 (26.3) | 189 (22.7) | 175 (18.8) | 150 (15.2) | |
| Reynold’s risk score (%) | 6.7 ± 7.2 | 7.4 ± 6.5 | 7.4 ± 7.5 | 6.8 ± 7.5 | 5.9 ± 6.7 | |
| Self-reported medical history, n (%) | ||||||
| Hypertension | 458 (25.7) | 97 (29.2) | 131 (27.2) | 146 (25.6) | 141 (23.8) | |
| Heart disease | 114 (6.4) | 5 (3.7) | 34 (7.1) | 30 (5.3) | 45 (7.6) | |
| Diabetes | 131 (7.4) | 18 (13.1) | 47 (9.8) | 36 (6.3) | 30 (5.0) | |
| Self-reported medication history, n (%) | ||||||
| Blood pressure-lowering med. | 382 (33.4) | 52 (29.7) | 113 (36.6) | 130 (34.2) | 117 (31.7) | |
| Cardiac med. | 325 (28.7) | 51 (31.1) | 87 (28.2) | 110 (29.0) | 105 (28.5) | |
| Diabetic med. | 83 (7.3) | 11 (14.9) | 31 (10.0) | 18 (4.7) | 23 (6.2) | |
| Use tobacco, n (%) * | 472 (15.9) | 65 (24.4) | 139 (17.0) | 131 (14.2) | 137 (14.4) | |
| Alcohol consumption, n (%) | 2350 (77.8) | 205 (74.8) | 633 (76.1) | 731 (78.7) | 781 (79.4) | |
| Physical activity, n (%) | ||||||
| Mild | 253 (53.6) | 22 (59.5) | 80 (53.7) | 79 (51.3) | 72 (54.6) | |
| Moderate | 154 (32.6) | 9 (24.3) | 52 (34.9) | 49 (31.8) | 44 (33.3) | |
| Strenuous | 16 (3.4) | 0 (0.0) | 3 (2.0) | 6 (3.9) | 7 (5.3) | |
| No physical activity | 49 (10.4) | 6 (16.3) | 14 (9.4) | 20 (13.0) | 9 (6.8) | |
| Fruit consumption, n (%) | ||||||
| None | 75 (3.0) | 11 (5.4) | 24 (3.6) | 25 (3.2) | 15 (1.8) | |
| 1 to 2 servings/day | 1189 (48.2) | 122 (59.8) | 344 (51.5) | 353 (45.3) | 370 (45.3) | |
| 3 to 4 servings/day | 949 (38.4) | 52 (25.5) | 245 (36.7) | 321 (41.1) | 331 (40.5) | |
| 5 & over servings/day | 256 (10.4) | 19 (9.3) | 55 (8.2) | 81 (10.4) | 101 (12.4) | |
| Vegetable consumption, n (%) | ||||||
| None | 24 (1.0) | 3 (1.5) | 7 (1.0) | 11 (1.4) | 3 (0.3) | |
| 1-2 servings/day | 949 (38.4) | 105 (51.2) | 280 (41.7) | 287 (36.7) | 277 (34.0) | |
| 3-4 servings/day | 1,049 (42.4) | 68 (33.2) | 283 (42.2) | 339 (43.4) | 359 (44.1) | |
| 5 & over servings/day | 451 (18.2) | 29 (14.1) | 101 (15.1) | 145 (18.5) | 176 (21.6) | |
| Fish consumption, n (%) | ||||||
| None | 241 (12.0) | 27 (16.7) | 66 (12.2) | 77 (12.2) | 71 (10.6) | |
| 1 serving/week | 453 (22.6) | 48 (29.6) | 118 (21.9) | 142 (22.4) | 145 (21.6) | |
| 2 servings/week | 636 (31.7) | 43 (26.5) | 166 (30.7) | 207 (32.7) | 220 (32.8) | |
| 3 & more servings/week | 675 (33.7) | 44 (27.2) | 190 (35.2) | 207 (32.7) | 234 (34.9) | |
Abbreviations: AA, arachidonic acid; BMI, body mass index; DBP, diastolic blood pressure; EPA, eicosapentaenoic acid; FBG, fasting blood glucose; HDL, high-density lipoproteins; HbA1c, hemoglobin A1c; hs-CRP, high sensitivity C-reactive protein; LDL, low-density lipoproteins; SBP, systolic blood pressure; SD, standard deviation; TG, Triglycerides; WC, waist circumference
To provide further context on the health of members of the program that engaged in the program and returned for follow-up and those that did not, we assessed baseline measures separately (Supplementary Table S3). In general, participants without follow-up had worse health outcomes than those with follow-up; however, mean values for both groups were still within normal ranges for all biomarkers.
Supplementary Table S3.
Comparison of characteristics of all participants at baseline, and baseline statistics for those with follow-up and those without recorded follow-up, roughly one year after entry.
| Program entry | With follow-up | Without follow-up | With vs. Without (P Value) | |
|---|---|---|---|---|
| Number of participants | 7939 | 3020 | 4,919 | |
| Age (year), mean (SD) | 60.2 ± 9.0 | 62.6 ± 8.6 | 58.8 ± 8.9 | <.01 |
| Gender, n (%) | <.01 | |||
| Female | 3443 (43.4) | 1607 (53.2) | 1,836 (37.3) | |
| Male | 4496 (56.6) | 1413 (46.8) | 3,083 (62.7) | |
| Ethnicity | ||||
| North American | 5164 (82.2) | 2410 (84.1) | 2,754 (80.6) | <.01 |
| Aboriginal | 334 (5.3) | 76 (2.6) | 258 (7.6) | <.01 |
| Asian | 331 (5.3) | 139 (4.9) | 192 (5.6) | .17 |
| European | 326 (5.2) | 204 (7.1) | 122 (3.5) | <.01 |
| African/Latin American | 131 (2.1) | 38 (1.3) | 93 (2.7) | <.01 |
| BMI (kg/m2) | 28.3 ± 5.5 | 27.8 ± 5.3 | 28.6 ± 5.6 | <.01 |
| BMI category, n (%) | ||||
| Underweight | 66 (0.8) | 21 (0.7) | 45 (0.9) | .30 |
| Normal weight | 2,211 (27.9) | 952 (31.6) | 1,259 (25.6) | <.01 |
| Overweight | 3,084 (38.9) | 1,168 (38.7) | 1,916 (39.0) | .84 |
| Obese | 2,568 (32.4) | 873 (29.0) | 1,695 (34.5) | <.01 |
| Ethnic-based obesity, n (%) | 2,142 (34.1) | 880 (30.7) | 1,262 (36.9) | <.01 |
| Abdominal obesity, n (%) | 3,722 (47.3) | 1,322 (44.0) | 2,400 (49.4) | <.01 |
| Ethnic-based abdominal obesity, n (%) | 2,200 (35.3) | 873 (30.6) | 1,327 (39.2) | <.01 |
| WC (cm) | 96.3 ± 14.6 | 94.0 ± 14.3 | 97.8 ± 14.6 | <.01 |
| SBP (mmHg) | 128.1 ± 16.9 | 126.8 ± 16.4 | 128.9 ± 17.1 | <.01 |
| DBP (mmHg) | 79.5 ± 9.9 | 78.8 ± 9.5 | 79.8 ± 10.0 | <.01 |
| Hypertension, n (%) | 2,535 (31.9) | 617 (27.8) | 2,138 (43.5) | <.01 |
| 25(OH)D (nmol/L) | 81 ± 35 | 91 ± 37 | 76 ± 33 | <.01 |
| Calcium (mmol/L) | 2.37 ± 0.11 | 2.38 ± 0.11 | 2.36 ± 0.10 | <.01 |
| Mean AA:EPA ratio | 16.1 ± 7.6 | 14.5 ± 7.2 | 17.5 ± 7.6 | <.01 |
| Vitamin B12 (pmol/L) | 458 ± 299 | 511 ± 318 | 426 ± 281 | <.01 |
| Homocysteine (μmol/L) | 10.8 ± 3.0 | 10.3 ± 2.8 | 11.1 ± 3.2 | <.01 |
| Normal, n (%) | 1168 (14.9) | 571 (19.0) | 597 (12.3) | <.01 |
| Low, n (%) | 4495 (57.3) | 1748 (58.2) | 2,747 (56.7) | .19 |
| High, n (%) | 2187 (27.9) | 685 (22.8) | 1,502 (31.0) | <.01 |
| hs-CRP (mg/L) | 2.48 ± 3.1 | 2.15 ± 2.7 | 2.68 ± 3.3 | <.01 |
| Low, n (%) | 2922 (36.8) | 1248 (41.3) | 1,674 (34.1) | <.01 |
| Intermediate, n (%) | 3116 (39.3) | 1183 (39.2) | 1,933 (39.3) | .89 |
| High, n (%) | 1898 (23.9) | 589 (19.5) | 1,309 (26.6) | <.01 |
| Inflammation (hs-CRP≥2 mg/L) | 3007 (37.8) | 987 (32.7) | 2,020 (41.1) | <.01 |
| Total cholesterol (mmol/L) | 5.13 ± 1.0 | 5.22 ± 1.0 | 5.07 ± 1.0 | <.01 |
| TG (mmol/L) | 1.36 ± 0.7 | 1.27 ± 0.6 | 1.42 ± 0.7 | <.01 |
| Hypertriglyceridemia, n (%) | 1,915 (24.1) | 588 (19.5) | 1,327 (27.0) | <.01 |
| HDL (mmol/L) | 1.48 ± 0.4 | 1.56 ± 0.5 | 1.43 ± 0.4 | <.01 |
| Low HDL, n (%) | 1,495 (18.8) | 1,470 (15.6) | 1,025 (20.8) | <.01 |
| LDL (mmol/L) | 3.04 ± 0.9 | 3.08 ± 0.9 | 3.02 ± 0.9 | <.01 |
| High LDL | 2370 (29.9) | 941 (31.2) | 1,429 (29.1) | .05 |
| Oxidized LDL (U/L) | 48.1 ± 13.7 | 48.0 ± 13.2 | 48.2 ± 14.1 | .59 |
| UbA1c, (%) | 5.83 ± 0.7 | 5.77 ± 0.5 | 5.87 ± 0.9 | <.01 |
| Prediabetes, n (%) | 2549 (32.1) | 1052 (35.0) | 1,497 (30.4) | <.01 |
| Diabetes, n (%) | 759 (9.6) | 208 (7.0) | 551 (11.2) | <.01 |
| FBG (mmol/L) | 5.22 ± 1.5 | 5.04 ± 1.1 | 5.33 ± 1.7 | <.01 |
| Hyperglycemia, n (%) | 1414 (18.0) | 428 (14.3) | 986 (20.3) | <.01 |
| Fasting insulin (pmol/L) | 62.7 ± 48.3 | 57.8 ± 41.2 | 65.7 ± 52.0 | <.01 |
| HOMA-IR | 2.78 ± 15.0 | 2.67 ± 17.2 | 2.85 ± 13.5 | .62 |
| Insulin resistance (≥2.73), n (%) | 1605 (20.5) | 486 (16.2) | 1,119 (23.1) | <.01 |
| Metabolic syndrome, n (%) | 1357 (17.1) | 403 (13.3) | 954 (19.4) | <.01 |
| Mean Framingham risk score, n (%) | 13.3 ± 8.5 | 12.3 ± 8.3 | 13.9 ± 8.6 | <.01 |
| Low | 3560 (44.8) | 1481 (49.0) | 2,079 (42.3) | <.01 |
| Intermediate | 2600 (32.8) | 953 (31.6) | 1,647 (33.5) | .08 |
| High | 1779 (22.4) | 586 (19.4) | 1,193 (24.2) | <.01 |
| Reynold’s risk score (%) | 6.8 ± 7.2 | 6.7 ± 7.2 | 6.8 ± 7.2 | .67 |
| High Reynold’s risk score (>10%), n (%) | 1473 (19.4) | 602 (20.6) | 871 (18.9) | .05 |
| Self-reported medical history, n (%) | ||||
| Hypertension | 1193 (25.2) | 458 (25.7) | 735 (24.8) | .49 |
| Heart disease | 333 (7.0) | 114 (6.4) | 219 (7.4) | .19 |
| Diabetes | 489 (10.3) | 131 (7.4) | 358 (12.1) | <.01 |
| Self-reported medication history, n (%) | ||||
| Blood pressure-lowering med. | 1169 (35.1) | 382 (33.4) | 787 (35.9) | .22 |
| Cardiac med. | 993 (29.9) | 325 (28.7) | 668 (30.5) | .30 |
| Diabetic med. | 404 (12.1) | 83 (7.3) | 321 (14.6) | <.01 |
| Use tobacco, n (%) | 1933 (25.0) | 472 (15.9) | 1,461 (69.2) | <.01 |
| Alcohol consumption, n (%) | 5824 (73.4) | 2350 (77.8) | 3,474 (70.6) | <.01 |
| Physical activity, n (%) | ||||
| None | 320 (18.6) | 49 (10.4) | 271 (21.7) | <.01 |
| Mild | 911 (53.0) | 253 (53.6) | 658 (52.7) | .75 |
| Moderate | 429 (24.9) | 154 (32.6) | 275 (22.0) | <.01 |
| Strenuous | 60 (3.5) | 16 (3.4) | 44 (3.6) | .89 |
| Fruit consumption, n (%) | ||||
| None | 242 (4.5) | 75 (3.0) | 167 (5.8) | <.01 |
| 1 to 2 servings/day | 2740 (51.1) | 1189 (48.2) | 1,551 (53.5) | <.01 |
| 3 to 4 servings/day | 1880 (35.0) | 949 (38.4) | 931 (32.1) | <.01 |
| 5 & over servings/day | 505 (9.4) | 256 (10.4) | 249 (8.6) | .03 |
| Vegetable consumption, n (%) | ||||
| None | 82 (1.5) | 24 (1.0) | 58 (2.0) | <.01 |
| 1 to 2 servings/day | 2336 (43.5) | 949 (38.4) | 1,387 (47.8) | <.01 |
| 3 to 4 servings/day | 2112 (39.3) | 1049 (42.4) | 1,063 (36.7) | <.01 |
| 5 & over servings/day | 842 (15.7) | 451 (18.2) | 391 (13.5) | <.01 |
| Fish consumption, n (%) | ||||
| None | 674 (14.6) | 241 (12.0) | 433 (16.6) | <.01 |
| 1 serving/week | 1,068 (23.1) | 453 (22.6) | 615 (23.5) | .45 |
| 2 servings/week | 1,399 (30.3) | 636 (31.7) | 763 (29.2) | .06 |
| 3 & more servings/week | 1,477 (32.0) | 675 (33.7) | 802 (30.7) | .03 |
Abbreviations: AA, arachidonic acid; BMI, body mass index; DBP, diastolic blood pressure; EPA, eicosapentaenoic acid; FBG, fasting blood glucose; HDL, high-density lipoproteins; HbA1c, hemoglobin A1c; hs-CRP, high sensitivity C-reactive protein; LDL, low-density lipoproteins; SBP, systolic blood pressure; SD, standard deviation; TG, triglycerides, WC, waist circumference.
In the subset of participants with Reynold’s risk score above 10% at baseline who were considered at high risk for CVD (n = 606), SBP, DBP, AA:EPA, homocysteine, total cholesterol, and HbA1c were significantly decreased after one year (Supplementary Table S4). Although still considered to be within the high risk range, mean Reynold’s risk scores were significantly reduced from 17.7 ± 8.4 to 16.7 ± 9.5 and mean Framingham risk scores were reduced from 23.9 ± 6.4 to 23.1 ± 7.3. In contrast, mean TG, Ox-LDL, and FBG levels were significantly increased, and HDL levels significantly decreased among these “high risk” participants.
Supplementary Table S4.
Longitudinal comparison of biometrics and biomarker measurements among participants of the Pure North program with high Reynold’s score (≥10%) considered at high risk for CVD.
| Baseline | Year 1 | P Value | |||
|---|---|---|---|---|---|
| n | Mean ± SD | n | Mean ± SD | ||
| BMI (kg/m2) | 591 | 29.0 ± 4.7 | 591 | 28.9 ± 4.8 | .2 |
| WC (cm) | 606 | 100.1 ± 12.1 | 606 | 99.9 ± 12.2 | .4 |
| SBP (mmHg) | 606 | 139.5 ± 16.4 | 606 | 136.2 ± 17.5 | <.01 |
| DBP (mmHg) | 606 | 81.8 ± 10.0 | 606 | 79.2 ± 9.6 | <.01 |
| 25(OH)D (nmol/L) | 606 | 87 ± 35 | 606 | 116 ± 37 | <.01 |
| Calcium (albumin corrected) (mmol/L) | 598 | 2.37 ± 0.1 | 598 | 2.34 ± 0.08 | <.01 |
| AA:EPA ratio | 143 | 14.0 ± 6.6 | 143 | 8.7 ± 5.6 | <.01 |
| Vitamin B12 (pmol/L) | 598 | 468 ± 288 | 598 | 1,509 ± 1,245 | <.01 |
| Homocysteine (μmol/L) | 282 | 11.4 ± 2.7 | 282 | 9.4 ± 1.9 | <.01 |
| hs-CRP (mg/L) | 606 | 2.60 ± 3.0 | 606 | 2.55 ± 3.0 | .2 |
| Total cholesterol (mmol/L) | 606 | 5.16 ± 1.0 | 606 | 5.09 ± 1.0 | .02 |
| TG (mmol/L) | 606 | 1.48 ± 0.7 | 606 | 1.53 ± 0.7 | .01 |
| HDL (mmol/L) | 606 | 1.35 ± 0.3 | 606 | 1.29 ± 0.3 | <.01 |
| LDL (mmol/L) | 601 | 3.16 ± 0.9 | 601 | 3.16 ± 0.9 | .9 |
| Ox-LDL (U/L) | 606 | 50.7 ± 13.5 | 606 | 54.1 ± 15.1 | <.01 |
| TG:HDL | 606 | 1.23 ± 0.8 | 606 | 1.32 ± 0.8 | .001 |
| Total cholesterob:HDL | 606 | 4.02 ± 1.1 | 606 | 4.11 ± 1.0 | .004 |
| Ox-LDL:LDL | 600 | 16.7 ± 4.2 | 600 | 17.8 ± 5.0 | <.01 |
| HbA1c (%) | 606 | 5.94 ± 0.7 | 606 | 5.83 ± 0.7 | <.01 |
| FBG (mmol/L) | 606 | 5.43 ± 1.3 | 606 | 5.66 ± 1.1 | <.01 |
| Fasting Insulin (pmol/L) | 524 | 68.8 ± 40.2 | 524 | 66.9 ± 37.4 | .1 |
| HOMA-IR | 524 | 2.47 ± 1.8 | 524 | 2.53 ± 1.7 | .3 |
| Framingham risk score | 606 | 23.9 ± 6.4 | 606 | 23.1 ± 7.3 | <.01 |
| Reynold’s risk score, % | 606 | 17.7 ± 8.4 | 606 | 16.7 ± 9.5 | <.01 |
Abbreviations: AA, arachidonic acid; BMI, body mass index; DBP, diastolic blood pressure; EPA, eicosapentaenoic acid; FBG, fasting blood glucose; HDL, high-density lipoproteins; HbA1c, hemoglobin A1c; hs-CRP, high sensitivity C-reactive protein; LDL, low-density lipoproteins; SBP, systolic blood pressure; SD, standard deviation; TG, triglycerides, WC, waist circumference.
We examined participant status for specific CVD risk parameters after one year to investigate the incidence of new cases of hypertension, obesity, inflammation, hypercholesterolemia, type 2 diabetes mellitus and high risk scores (Table 3). The results did not differ when participants taking medications relevant to the CVD risk factor were excluded from the analysis (Table 3), and the results discussed here are for those not taking relevant medications. Of the 397 participants who were hypertensive at baseline, 7.6% were normotensive at follow-up; 6.1% of participants who were normotensive at baseline were newly classified as hypertensive at follow-up (“new cases”). Hypertriglyceridemia was initially reported in 588 participants at baseline of whom 32.8% did not have hypertriglyceridemia at follow-up. Of participants without hypertriglyceridemia, 13.1% were identified as new cases of hypertriglyceridemia at follow-up. Of the 470 participants with low HDL levels at baseline, 33.8% had HDL levels within the reference range at follow-up; whereas of the 2,550 participants within the reference range at baseline, 7.6% were identified as new cases of low HDL. For the 428 participants that were hyperglycemic at baseline, 29.2% were normoglycemic at follow-up. Of the 2 573 non-hyperglycemic individuals at baseline, 11.8% developed hyperglycemia by follow-up.
Table 3.
Differences in the incidence of cardiovascular disease risk parameters within participants of the Pure North program (n = 3020, with some missing responses) between baseline and follow-up (one year).
| Cardiovascular disease risk parameter | Present at baseline | Present at follow-up, n (%) | Excluding those taking related medications, n (%) | ||
|---|---|---|---|---|---|
| Yes | No | Yes | No | ||
| High BMI | Yes | 759 (89.0) | 94 (11.0) | – | – |
| No | 100 (4.9) | 1927 (95.1) | – | – | |
| Abdominal obesity | Yes | 1121 (84.8) | 201 (15.2) | – | – |
| No | 194 (11.5) | 1 491 (88.5) | – | – | |
| Hypertension | Yes | 367 (92.4) | 30 (7.6) | 203 (91.0) | 20 (9.0) |
| No | 161 (6.1) | 2462 (93.9) | 96 (5.2) | 1,745 (94.8) | |
| Inflammation | Yes | 673 (69.5) | 295 (30.5) | – | – |
| No | 289 (14.3) | 1732 (85.7) | – | – | |
| High total cholesterol | Yes | 1174 (78.5) | 322 (21.5) | – | – |
| No | 316 (20.9) | 1197 (79.1) | – | – | |
| Hypertriglyceridemia | Yes | 395 (67.2) | 193 (32.8) | 208 (62.8) | 123 (37.2) |
| No | 318 (13.1) | 2114 (86.9) | 202 (12.2) | 1,459 (87.8) | |
| Low HDL | Yes | 311 (66.1) | 159 (33.8) | 168 (62.0) | 103 (38.0) |
| No | 194 (7.6) | 2356 (92.4) | 108 (6.3) | 1,613 (93.7) | |
| High LDL | Yes | 684 (72.7) | 257 (27.3) | – | – |
| No | 309 (14.9) | 1770 (85.1) | – | – | |
| High Ox-LDL | Yes | 47 (37.0) | 80 (63.0) | – | – |
| No | 207 (7.3) | 2649 (92.8) | – | – | |
| Prediabetes | Yes | 461 (43.7) | 594 (56.3) | 301 (40.3) | 446 (59.7) |
| No | 179 (9.2) | 1766 (90.8) | 110 (7.6) | 1,337 (92.4) | |
| Diabetes | Yes | 133 (64.6) | 73 (35.4) | 29 (49.2) | 30 (50.1) |
| No | 37 (1.3) | 2757 (98.7) | 10 (0.5) | 2,125 (99.5) | |
| Elevated FBG | Yes | 303 (70.8) | 125 (29.2) | 126 (61.2) | 80 (38.8) |
| No | 304 (11.8) | 2 269 (88.2) | 200 (10.1) | 1,785 (89.9) | |
| Insulin resistance | Yes | 299 (64.4) | 166 (35.6) | 138 (57.5) | 102 (42.5) |
| No | 191 (9.6) | 1804 (90.4) | 124 (8.2) | 1,398 (91.9) | |
| Metabolic syndrome | Yes | 261 (64.8) | 142 (35.2) | – | – |
| No | 227 (8.7) | 2390 (91.3) | – | – | |
| Intermediate Framingham risk score | Yes | 487 (51.4) | 460 (48.6) | – | – |
| No | 451 (21.9) | 1611 (78.1) | – | – | |
| High Framingham risk score | Yes | 418 (71.7) | 165 (28.3) | – | – |
| No | 253 (10.4) | 2173 (89.6) | – | – | |
| High Reynold’s risk score | Yes | 434 (75.9) | 138 (24.1) | – | – |
| No | 171 (7.5) | 2113 (92.5) | – | – | |
For elevated FBG, diabetics, prediabetics, and participant that were insulin resistance or on diabetic medications were excluded. For hypertension, participants on blood pressure-lowering medications were excluded. For hypertriglyceridemia and low HDL, participants on lipid-lowering medications were excluded. For all the CVD risk parameters listed above, participants on cardiac medications were excluded.
Abbreviations: HDL, high-density lipoproteins; LDL, low-density lipoproteins; Ox-LDL, Oxidized LDL.
Of the 1 055 participants considered prediabetic at baseline, 56.3% were within the reference range at follow-up, whereas 9.2% of normoglycemics at baseline were new cases of prediabetes at follow-up. Of the 465 insulin resistant participants at baseline, 35.6% were no longer insulin resistant at follow-up versus 9.6% new cases identified. Inflammation (hs-CRP ≥2 mg/L) was detected in 968 participants at baseline, 30.5% had hs-CRP values <2 mg/L at follow-up, vs. 14.3% new cases identified. At baseline, 947 participants had an intermediate Framingham risk score and 583 participants had a high risk score, of whom 48.6% and 28.3%, respectively, had a lower risk score at follow-up. Of those with a low Framingham risk score at baseline, 21.9% were new cases of intermediate risk and 10.4% new cases of high risk at follow-up. At baseline 572 participants had high Reynold’s risk scores (>10%) and 24.1% of these participants were at low risk at follow-up in comparison to 7.5% of new cases identified.
Of the 3 020 participants with information recorded at baseline and at follow-up, 867 reported taking cardiovascular-modifying medication at baseline or follow-up. There were 281 participants taking cardiac medication at baseline but 40 (14%) were able to discontinue cardiac medication use at follow-up; 56 (3%) new participants were prescribed a cardiac medication between baseline and follow-up. There were 320 participants taking anti-hypertensive medication at baseline, of whom 43 (13%) had discontinued medication at follow-up; 56 (3%) new participants were prescribed anti-hypertensive medication between baseline and one year. Diabetes medications were taken by 83 participants at baseline, 10 (12%) of whom were no longer taking these at follow-up and 12 (<1%) new participants began taking diabetes medication after baseline.
To characterize the impact of nutritional supplements on CVD risk parameters we investigated changes with respect to changes in available nutritional markers: serum 25(OH)D, vitamin B12, and AA:EPA (Table 4). Serum 25 (OH) concentrations were significantly positively correlated with HDL, total cholesterol, and LDL. Serum 25(OH)D concentrations were also significantly negatively correlated with BMI, WC, DBP, AA:EPA, homocysteine, hs-CRP, TG, Ox-LDL, HbA1c, FBG, and fasting insulin. A significant negative correlation between 25(OH)D and Framingham score was found but there was no association with the Reynold’s risk score.
Table 4.
Correlation between nutritional markers (serum 25(OH)D, vitamin B12, AA:EPA) and CVD risk parameters after one year of treatment.
| Cardiovascular disease risk parameters | n | Serum 25(OH)D | Serum vitamin B12 | n | AA:EPA ratio |
|---|---|---|---|---|---|
| BMI | 2880 | -0.22a | -0.02 | 742 | 0.18a |
| WC | 3020 | -0.21a | -0.05b | 778 | 0.21a |
| SBP | 3020 | -0.02 | 0.03 | 778 | 0.05 |
| DBP | 3020 | -0.05a | -0.04b | 778 | 0.03 |
| Calcium | 3013 | 0.12a | 0.02 | 773 | -0.03 |
| AA:EPA ratio | 778 | -0.37a | -0.15a | ||
| Homocysteine | 1530 | -0.11a | -0.16a | 767 | 0.26a |
| hs-CRP | 2989 | -0.09a | 0.01 | 771 | 0.10a |
| Total cholesterol | 3009 | 0.08a | 0.01 | 775 | -0.14a |
| TG | 3020 | -0.15a | -0.04b | 778 | 0.09a |
| HDL | 3020 | 0.17a | 0.05a | 778 | -0.17a |
| LDL | 3020 | 0.07a | 0.01 | 778 | -0.12a |
| Ox-LDL | 3007 | -0.03 | -0.02 | 778 | -0.09a |
| TG:HDL | 3020 | -0.16a | -0.04b | 778 | 0.11a |
| Total cholesterol:HDL | 3009 | -0.10a | -0.04b | 775 | 0.03 |
| Ox-LDL:LDL | 3007 | -0.11a | -0.01 | 778 | 0.03 |
| HbA1c | 3013 | -0.08a | 0.03 | 775 | 0.015a |
| FBG | 3020 | -0.09a | 0.05* | 778 | 0.06 |
| Insulin | 2482 | -0.12a | -0.01 | 651 | 0.09* |
| Framingham risk score | 3009 | -0.04b | -0.02 | 775 | 0.12** |
| Reynold’s risk score | 2938 | -0.01 | 0.02 | 754 | 0.04 |
aCorrelation is significant at the .01 level (2-tailed)
bCorrelation is significant at the .05 level (2-tailed)
Abbreviations: AA, arachidonic acid; BMI, body mass index; DBP, diastolic blood pressure; EPA, eicosapentaenoic acid; FBG, fasting blood glucose; HDL, high-density lipoproteins; hs-CRP, high sensitivity C-reactive protein; LDL, low-density lipoproteins; Ox-LDL, Oxidized LDL; PMH, past medical history; SBP, systolic blood pressure; SD, standard deviation; TG, fasting triglycerides, WC, waist circumference
Vitamin B12 concentrations were positively associated with HDL and FBG and negatively correlated with WC, DBP, AA:EPA, homocysteine, and TG. Mean AA:EPA concentrations were available for only a subset of the population (n = 778) but were significantly negatively correlated with total cholesterol, HDL, LDL, and Ox-LDL, and positively correlated with BMI, WC, homocysteine, hs-CRP, TG, HbA1c, fasting insulin, and Framingham risk score. Results did not differ when participants with a history of CVD disease or use of cardiac medication were excluded from the analyses (data not shown).
Because serum 25(OH)D concentrations were associated with 90% of the CVD risk parameters investigated (versus 43% for vitamin B12 and 52% for AA:EPA), relative risk models were performed to investigate the association between optimized 25(OH)D concentrations (≥100 nmol/L) with prevalence of CVD risk parameters (Table 5). Having suboptimal 25(OH)D concentrations (<100 nmol/L) was significantly associated with increased risk for abdominal obesity, hypertension, hypertriglyceridemia, inflammation (hs-CRP ≥ 2), low HDL, metabolic syndrome, insulin resistance, prediabetes and diabetes. The prevalence of CVD risk factors was 9-53% higher with serum 25(OH)D concentrations <100 nmol/L.
Table 5.
Relative risk for cardiovascular risk parameters according to participants who reached and maintained a serum 25(OH)D concentration < 100 nmol/L at follow-up (n= 1081 for most variables) and those who did not (n= 1939 for most variables).
| Cardiovascular disease risk parameter | <100 nmol/L, n (%) | >100 nmol/L, n (%) | Relative risk (95% CI) |
|---|---|---|---|
| Abdominal obesity | 572 (53%) | 755 (39%) | 1.43 (1.30 to 1.58) |
| Ethnic-based abdominal obesity | 403 (39%) | 453 (25%) | 1.51 (1.38 to 1.67) |
| Hypertension | 220 (20%) | 308 (16%) | 1.21 (1.08 to 1.35) |
| Inflammation (≥3 mg/L) | 273 (26%) | 339 (18%) | 1.34 (1.20 to 1.48) |
| Inflammation (≥2 mg/L) | 412 (39%) | 550 (29%) | 1.33 (1.20 to 1.46) |
| Hypertriglyceridemia | 310 (29%) | 403 (21%) | 1.30 (1.18 to 1.44) |
| Low HDL | 235 (22%) | 270 (14%) | 1.38 (1.24 to 1.54) |
| High LDL | 328 (30%) | 665 (34%) | 0.89 (0.80 to 0.99) |
| Elevated FBG | 261 (24%) | 350 (18%) | 1.25 (1.13 to 1.40) |
| Prediabetes | 253 (23%) | 390 (20%) | 1.13 (1.01 to 1.26) |
| Diabetes | 94 (9%) | 79 (4%) | 1.57 (1.35 to 1.81) |
| Insulin resistance | 230 (25%) | 266 (17%) | 1.32 (1.18 to 1.48) |
| Metabolic syndrome | 233 (22%) | 255 (13%) | 1.43 (1.28 to 1.59) |
| Framingham risk level (≥10%) | 259 (24%) | 412 (21%) | 1.10 (0.99 to 1.23) |
| Reynold’s risk score (≥5%) | 218 (21%) | 405 (22%) | 0.97 (0.86 to 1.10) |
Multivariate logistic regression analyses revealed a significant association between elevated 25(OH)D concentrations and reductions in most of the CVD risk parameters, even after adjusting for covariates such as age, gender, vitamin B12, AA:EPA ratios, tobacco use, presence of inflammation, and fruit consumption (Table 6); univariate analyses of the CVD risk parameters are provided in the supplementary materials (Supplementary Tables S5-S15). Achieving serum 25(OH)D concentrations ≥75 nmol/L significantly reduced the odds of hypertension (P =.04) and inflammation (P=.O3), and 25(OH)D concentrations ≥100 nmol/L significantly reduced the risk of metabolic syndrome (p = .05), hypertriglyceridemia (P = .05), low HDL (P = .02), and diabetes (P =0.05). Serum 25(OH)D concentrations ≥125 nmol/L significantly reduced the odds of abdominal obesity (p = .O5). The odds of having a high Framingham score were reduced with 25(OH)D concentrations ≥125 nmol/L (P = .O5).
Table 6.
Odds for cardiovascular risk parameters at follow-up, after one year of treatment. Binary Logistic Regression Models adjusted for all the covariates which were significant predictor in univariate analyses.
| Cardiovascular disease risk parameter | After one year of treatment | OR | 95% CI | P value |
|---|---|---|---|---|
| Ethnic-based abdominal obesity (n = 485, R2 = 0.13, P<.001) |
Age | 1.02 | 1.01 to 1.03 | .002a |
| Gender (male) | 3.08 | 2.16 to 4.40 | <.001a | |
| 25(OH)D (<50 nmol/L) | Ref. | .005a | ||
| 50 to <75 | 0.40 | 0.06 to 2.57 | .3 | |
| 75 to <100 | 0.36 | 0.06 to 2.20 | .2 | |
| 100 to <125 | 0.24 | 0.04 to 1.50 | .1 | |
| ≥125 | 0.16 | 0.03 to 1.00 | .05a | |
| Vitamin B19 (pmol/L) | 1.00 | 1.00 to 1.00 | .2 | |
| AA:EPA | 1.01 | 0.98 to 1.05 | .4 | |
| Current smoking (yes) | 1.00 | 0.61 to 1.63 | .9 | |
| Inflammation (hs-CRP>2) | 4.25 | 2.98 to 6.06 | <.001a | |
| Fruit consumption (no) | Ref. | .08 | ||
| 1 to 2 servings/day | 1.35 | 0.41 to 5.31 | .6 | |
| 3 to 4 servings/day | 1.61 | 0.49 to 5.31 | .4 | |
| 5 & more servings/day | 0.77 | 0.22 to 2.72 | .6 | |
| Hypertension (n = 330, R2 = 0.21, P<.001) |
Age | 1.02 | 1.01 to 1.03 | .001a |
| Gender (male) | 1.83 | 1.03 to 3.25 | .03a | |
| Ethnicity (North American) | Ref. | .05a | ||
| Aboriginal | 0.76 | 0.17 to 3.48 | .7 | |
| Asian | 0.27 | 0.06 to 1.30 | .1 | |
| European | 2.49 | 0.87 to 7.10 | .08 | |
| African/Latin American | 2.50 | 0.48 to 13.07 | .2 | |
| 25(OH)D (<50 nmol/L) | Ref. | .1 | ||
| 50 to <75 nmol/L | 0.50 | 0.17 to 1.50 | .2 | |
| 75 to <100 | 0.33 | 0.11 to 0.98 | .04a | |
| 100 to <125 | 0.37 | 0.13 to 1.00 | .05a | |
| ≥125 | 0.41 | 0.14 to 1.22 | .1 | |
| Vitamin B19 (pmol/L) | 1.00 | 1.00 to 1.00 | .4 | |
| AA:EPA | 0.98 | 0.92 to 1.04 | .5 | |
| Ethnic-based BMI (kg/m2) | 2.50 | 1.37 to 4.58 | .003a | |
| PMH (hypertension) at baseline | 2.65 | 1.91 to 3.69 | <.001a | |
| Hypertension medication (yes) | 1.08 | 0.51 to 2.30 | .8 | |
| Inflammation (hs-CRP>2) | 1.27 | 0.97 to 1.67 | .08 | |
| Alcohol drinking (yes) | 1.37 | 1.03 to 1.84 | .03a | |
| Hypertriglyceridemia (n = 646, R2 = 0.15, P<.001) | Age | 1.02 | 1.01 to 1.03 | .002a |
| Gender (male) | 1.41 | 1.04 to 1.90 | .02a | |
| Ethnicity (North American) | Ref. | .1 | ||
| Aboriginal | 2.02 | 1.10 to 3.71 | .02a | |
| Asian | 0.93 | 0.51 to 1.68 | .8 | |
| European | 0.90 | 0.43 to 1.88 | .8 | |
| African/Latin American | 0.51 | 0.17 to 1.59 | .2 | |
| 25(OH)D (<50 nmol/L) | Ref. | <.001a | ||
| 50 to <75 | 0.94 | 0.28 to 3.20 | .9 | |
| 75 to <100 | 0.66 | 0.20 to 2.19 | .4 | |
| 100 to <125 | 0.36 | 0.27 to 0.89 | .05a | |
| ≥125 | 0.35 | 0.14 to 0.91 | .05a | |
| Vitamin B19 (pmol/L) | 1.00 | 1.00 to 1.00 | .4 | |
| AA:EPA | 0.97 | 0.95 to 1.01 | .1 | |
| Ethnic-based BMI (kg/m2) | 2.97 | 2.17 to 4.08 | <.001a | |
| Current smoking (yes) | 1.45 | 0.99 to 2.14 | .06 | |
| Alcohol drinking (yes) | 0.94 | 0.66 to 1.33 | .7 | |
| Inflammation (hs-CRP≥2) | 1.25 | 0.91 to 1.73 | .1 | |
| Low HDL (n = 417, R2 = 0.10, P<.001) |
Age | 1.002 | 0.99 to 1.02 | .7 |
| Gender (male) | 0.68 | 0.55 to 0.84 | <.001a | |
| Ethnicity (North American) | Ref. | .6 | ||
| Aboriginal | 0.81 | 0.27 to 2.40 | .7 | |
| Asian | 0.64 | 0.28 to 1.47 | .2 | |
| European | 0.51 | 0.17 to 1.55 | .2 | |
| African/Latin American | 1.18 | 0.27 to 5.13 | .8 | |
| 25(OH)D (<50 nmol/L) | Ref. | .01a | ||
| 50 to <75 | 0.98 | 0.10 to 9.89 | .9 | |
| 75 to < 100 | 0.47 | 0.20 to 1.10 | .08 | |
| 100 to <125 | 0.37 | 0.16 to 0.89 | .02a | |
| ≥125 | 0.38 | 0.16 to 0.90 | .03a | |
| Vitamin B19 (pmol/L) | 1.00 | 1.00 to 1.00 | .3 | |
| AA:EPA | 1.01 | 0.97 to 1.05 | .7 | |
| Ethnic-based BMI (kg/m2) | 3.05 | 2.01 to 4.63 | <.001a | |
| Inflammation (hs-CRP>2) | 1.69 | 1.11 to 2.56 | .01a | |
| Fish consumption (No) | Ref. | .1 | ||
| One serving/week | 0.64 | 0.35 to 1.18 | .1 | |
| Two servings/week | 0.76 | 0.43 to 1.36 | .3 | |
| 3 & more servings/week | 0.53 | 0.29 to 0.95 | .03a | |
| Current smoking (yes) | 1.02 | 0.58 to 1.79 | .9 | |
| Elevated FBG (n = 202, R2 = 0.44, P<.001) |
Age | 1.06 | 1.03 to 1.08 | <.001a |
| Gender (male) | 1.75 | 0.95 to 3.23 | .07 | |
| Ethnicity (North American) | Ref. | .6 | ||
| Aboriginal | 0.53 | 0.06 to 5.18 | .5 | |
| Asian | 1.05 | 0.33 to 3.33 | .9 | |
| European | 0.40 | 0.08 to 1.95 | .2 | |
| African/Latin American | 3.85 | 0.28 to 52.91 | .3 | |
| 25(OH)D (<50 nmol/L) | Ref. | .1 | ||
| 50 to <75 | 0.32 | 0.05 to 1.95 | .2 | |
| 75 to <100 | 0.44 | 0.08 to 2.58 | .3 | |
| 100 to <125 | 0.37 | 0.06 to 2.18 | .2 | |
| ≥125 | 0.28 | 0.04 to 1.67 | .1 | |
| Vitamin B12 (pmol/L) | 1.00 | 1.00 to 1.00 | .1 | |
| AA:EPA | 0.99 | 0.93 to 1.06 | .8 | |
| Ethnic-based BMI (kg/m2) | 4.77 | 2.51 to 9.08 | <.001a | |
| Inflammation (hs-CRP≥2) | 1.43 | 0.76 to 2.69 | .2 | |
| PMH (diabetes) at baseline | 11.8 | 3.90 to 36.10 | <.001a | |
| Diabetic medication (yes) | 8.26 | 4.40 to 15.51 | <.001a | |
| Fruit consumption (no) | Ref. | .8 | ||
| 1 to 2 servings/day | 0.43 | 0.06 to 3.12 | .4 | |
| 3 to 4 servings/day | 0.38 | 0.05 to 2.81 | .3 | |
| 5 & more servings/day | 0.46 | 0.06 to 3.88 | .4 | |
| Metabolic syndrome (n = 289, R2 = 0.26, P<.001) |
Age | 1.01 | 1.00 to 1.03 | .09 |
| Gender (male) | 0.98 | 0.68 to 1.42 | .9 | |
| Ethnicity (North American) | Ref. | .01 | ||
| Aboriginal | 0.14 | 0.03 to 0.68 | .01a | |
| Asian | 0.32 | 0.14 to 0.73 | .007a | |
| European | 0.95 | 0.47 to 1.97 | .9 | |
| African/Latin American | 0.75 | 0.22 to 2.50 | .6 | |
| 25(OH)D (<50 nmol/L) | Ref. | .5 | ||
| 50 to <75 | 0.30 | 0.05 to 2.10 | .2 | |
| 75 to <100 | 0.37 | 0.06 to 2.49 | .3 | |
| 100 to <125 | 0.28 | 0.04 to 1.00 | .05a | |
| ≥125 | 0.28 | 0.04 to 1.00 | .05a | |
| Vitamin B12 (≥ 450 pmol/L) | 1.00 | 1.00 to 1.00 | .2 | |
| Ethnic-based BMI (kg/m2) | 6.65 | 4.57 to 9.71 | <.001a | |
| Inflammation (hs-CRP ≥2) | 1.18 | 0.82 to 1.69 | .3 | |
| AA:EPA | 1.04 | 0.97 to 1.12 | .3 | |
| Alcohol drinking (yes) | 1.32 | 0.57 to 3.09 | .5 | |
| PMH (hypertension) | 1.78 | 1.23 to 2.58 | .002a | |
| PMH (diabetes) | 4.62 | 2.81 to 7.61 | <.001a | |
| Fish consumption (No) | Ref. | .7 | ||
| One serving/week | 0.90 | 0.35 to 2.31 | .8 | |
| Two servings/week | 0.75 | 0.30 to 1.89 | .5 | |
| 3 & more servings/week | 0.65 | 0.26 to 1.63 | .3 | |
| Insulin resistance (n = 356, R2 = 0.41, P<.001) |
Age | 1.01 | 0.99 to 1.03 | .5 |
| Gender (male) | 2.31 | 1.39 to 3.87 | .001a | |
| Ethnicity (North American) | Ref. | .2 | ||
| Aboriginal | 3.23 | 1.00 to 10.64 | .05a | |
| Asian | 0.54 | 0.20 to 1.49 | .2 | |
| European | 0.80 | 0.26 to 2.45 | .7 | |
| African/Latin American | 0.71 | 0.14 to 3.57 | .6 | |
| 25(OH)D (<50 nmol/L) | Ref. | .02 | ||
| 50-<75 | 0.81 | 0.06 to 12.09 | .8 | |
| 75-<100 | 0.50 | 0.04 to 7.34 | .6 | |
| 100-<125 | 0.27 | 0.02 to 4.02 | .3 | |
| ≥125 | 0.20 | 0.01 to 3.08 | .2 | |
| Vitamin B12 (pmol/L) | 1.00 | 1.00 to 1.00 | .4 | |
| Ethnic-based BMI (kg/m2) | 9.09 | 5.24 to 15.77 | <.001a | |
| Inflammation (hs-CRP≥2) | 1.58 | 0.92 to 2.72 | .09 | |
| AA:EPA | 0.94 | 0.89 to 0.99 | .01a | |
| Alcohol drinking (yes) | 0.84 | 0.47 to 1.50 | .5 | |
| PMH (diabetes) | 11.71 | 4.57 to 30.06 | <.001a | |
| Diabetes (n=422, R2 = 0.43, P<.001) |
Age | 1.04 | 1.01 to 1.07 | .01a |
| Gender (male) | 1.97 | 0.96 to 4.07 | .06 | |
| Ethnicity (North American) | Ref. | .01a | ||
| Aboriginal | 1.14 | 0.19 to 6.91 | .8 | |
| Asian | 5.11 | 1.85 to 14.11 | .002a | |
| European | 1.02 | 0.19 to 5.45 | .9 | |
| African/Latin American | 6.34 | 1.20 to 33.44 | .02a | |
| 25(OH)D (< 50 nmol/L) | Ref. | .6 | ||
| 50 to <75 | 0.23 | 0.02 to 3.26 | .2 | |
| 75 to <100 | 0.28 | 0.02 to 3.55 | .3 | |
| 100 to <125 | 0.19 | 0.02 to 1.00 | .05a | |
| ≥125 | 0.17 | 0.01 to 1.00 | .05a | |
| Ethnic-based BMI, kg/m2 | 3.59 | 1.66 to 7.74 | .001a | |
| Inflammation (hs-CRP≥2) | 1.83 | 0.84 to 3.99 | .1 | |
| Vitamin B12, pmol/L | 1.00 | 1.00 to 1.00 | .8 | |
| AA:EPA | 0.98 | 0.91 to 1.05 | .9 | |
| PMH (diabetes) at baseline | 40.27 | 16.98 to 95.48 | <.001a | |
| Framingham high risk level (n = 644, R2 = 0.59, P<.001) |
Age | 1.20 | 1.17 to 1.24 | <.001a |
| Gender (male) | 59.4 | 27.93 to 126.30 | <.001a | |
| Ethnicity (North American) | Ref. | .7 | ||
| Aboriginal | 0.97 | 0.26 to 3.68 | .9 | |
| Asian | 0.77 | 0.26 to 2.31 | .6 | |
| European | 1.39 | 0.51 to 3.79 | .5 | |
| African/Latin American | 2.11 | 0.50 to 8.98 | .3 | |
| 25(OH)D (<50 nmol/L) | Ref. | .4 | ||
| 50 to <75 | 1.26 | 0.10 to 15.33 | .8 | |
| 75 to <100 | 0.97 | 0.09 to 11.21 | .9 | |
| 100 to <125 | 0.77 | 0.07 to 8.80 | .6 | |
| ≥125 | 0.58 | 0.05 to 0.99 | .05a | |
| Currently smoking (yes) | 4.92 | 2.44 to 9.90 | <.001a | |
| Alcohol drinking (yes) | 1.38 | 0.76 to 2.51 | .2 | |
| Ethnic-based BMI (kg/m2) | 4.41 | 2.56 to 7.58 | <.001” | |
| Inflammation (hs-CRP≥2) | 1.20 | 0.71 to 2.04 | .4 | |
| Vitamin B12 (pmol/L) | 1.00 | 1.00 to 1.00 | .08 | |
| AA:EPA | 0.94 | 0.90 to 1.00 | .054 | |
| Reynold’s risk score (n = 637, R2 = 0.63, P<.001) |
Age | 1.31 | 1.25 to 1.38 | <.001a |
| Gender (male) | 31.6 | 14.45 to 69.30 | <.001a | |
| Ethnicity (North American) | Ref. | .2 | ||
| Aboriginal | 2.89 | 0.78 to 10.71 | .1 | |
| Asian | 0.19 | 0.03 to 1.20 | .07 | |
| European | 1.10 | 0.36 to 3.36 | .8 | |
| African/Latin American | 1.30 | 0.21 to 8.02 | .7 | |
| 25(OH)D (<50 nmol/L) | Ref. | .4 | ||
| 50 to <75 | 1.26 | 0.10 to 15.33 | .8 | |
| 75 to <100 | 0.97 | 0.09 to 11.21 | .9 | |
| 100 to <125 | 0.50 | 0.15 to 1.67 | .2 | |
| ≥125 | 0.59 | 0.18 to 1.97 | .3 | |
| Ethnic-based BMI (kg/m2) | 2.30 | 1.25 to 4.24 | .008a | |
| Currently smoking (yes) | 6.90 | 2.98 to 15.98 | <.001a | |
| Alcohol drinking (yes) | 1.46 | 0.72 to 2.98 | .2 | |
| Inflammation (hs-CRP≥2) | 2.27 | 1.25 to 4.14 | .007a | |
| Vitamin B12, pmol/L | 1.00 | 1.00 to 1.00 | .01a | |
| AA:EPA | 0.97 | 0.92 to 1.04 | .5 | |
| Inflammation (n = 646, R2 = 0.19, P<.001) |
Age | 1.01 | 1.00 to 1.02 | .01a |
| Gender (male) | 0.71 | 0.55 to 0.93 | .01a | |
| Ethnicity (North American) | Ref. | .06 | ||
| Aboriginal | 1.48 | 0.82 to 2.67 | .1 | |
| Asian | 0.47 | 0.26 to 0.86 | .01a | |
| European | 1.19 | 0.64 to 2.23 | .5 | |
| African/Latin American | 0.69 | 0.28 to 1.71 | .4 | |
| 25(OH)D (<50 nmol/L) | Ref. | .001a | ||
| 50 to <75 | 0.75 | 0.43 to 1.32 | .3 | |
| 75 to <100 | 0.56 | 0.32 to 0.97 | .03a | |
| 100 to <125 | 0.50 | 0.29 to 0.87 | .01a | |
| ≥125 | 0.51 | 0.29 to 0.88 | .01a | |
| Ethnic-based BMI (kg/m2) | 4.24 | 3.22 to 5.60 | <.001a | |
| Currently smoking (yes) | 1.59 | 1.12 to 2.27 | .01a | |
| Vitamin B12 (pmol/L) | 1.00 | 1.00 to 1.00 | .1 | |
| AA:EPA | 1.02 | 1.00 to 1.05 | .09 |
aCorrelation is significant at the .05 level (2-tailed)
Abbreviations: AA, arachidonic acid; BMI, body mass index; EPA, eicosapentaenoic acid; CI, confidence interval; LDL, low-density lipoproteins; OR, odds ratio; PMH, past medical history.
Supplementary Table S5.
Univariate analyses for abdominal obesity at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 2867 | 0.99 | 0.98 to 1.00 | .19 |
| Gender | 2867 | |||
| Female | Ref. | |||
| Male | 2.06 | 1.76 to 2.43 | <.01 | |
| BMI at baseline (kg/m2) | 2840 | |||
| Underweight | Ref. | |||
| Normal weight | 0.10 | 0.01 to 0.02 | <.01 | |
| Overweight | 0.09 | 0.07 to 0.11 | <.01 | |
| Obese | ||||
| Baseline abdominal obesity | 2855 | |||
| Non-obese | Ref. | |||
| Obese | 15.56 | 12.58 to 19.26 | <.01 | |
| Baseline 25(OH)D (nmol/L) | 2867 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.80 | 0.60 to 1.06 | .12 | |
| 75 to <100 | 0.44 | 0.33 to 0.59 | <.01 | |
| 100 to <125 | 0.30 | 0.220.42 | <.01 | |
| ≥125 | 0.22 | 0.15 to 0.32 | <.01 | |
| Year 1 25(OH)D (nmol/L) | 2867 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.53 | 0.20 to 1.41 | .21 | |
| 75 to <100 | 0.36 | 0.14 to 0.93 | .04 | |
| 100 to <125 | 0.25 | 0.10 to 0.66 | <.01 | |
| ≥125 | 0.17 | 0.07 to 0.45 | <.01 | |
| Baseline AA:EPA | 2582 | 1.04 | 1.03 to 1.05 | <.01 |
| Baseline vitamin B12 (pmol/L) | 2859 | |||
| <450 | Ref. | |||
| ≥450 | 0.62 | 0.52 to 0.73 | <.01 | |
| Year 1 vitamin B12 (pmol/L) | 2845 | |||
| <450 | Ref. | |||
| ≥450 | 0.67 | 0.51 to 0.88 | <.01 | |
| Past medical history | 2867 | |||
| No past medical history | Ref. | |||
| Hypertension | 2.49 | 2.00 to 3.11 | <.01 | |
| Heart disease | 1.41 | 0.94 to 2.11 | <.01 | |
| Diabetes | 2.52 | 1.74 to 3.67 | <.01 | |
| Past medication history | 2867 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 1.70 | 1.35 to 2.13 | <.01 | |
| Cardiac medication | 1.60 | 1.21 to 2.11 | <.01 | |
| Currently smoking at baseline | 2824 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.17 | 0.94 to 1.47 | .15 | |
| Alcohol consumption at baseline | 2866 | |||
| None | Ref. | |||
| Drinking in past year | 0.72 | 0.60 to 0.87 | <.01 | |
| Physical activity at baseline | 455 | |||
| Mild | Ref. | |||
| Moderate | 0.84 | 0.53 to 1.33 | .47 | |
| Strenuous | 0.60 | 0.16 to 2.19 | .44 | |
| No physical activity | 2.10 | 1.10 to 4.02 | .02 | |
| Fruit consumption at baseline | 2405 | |||
| None | Ref. | |||
| 1-2 servings/day | 1.11 | 0.66 to 1.87 | .70 | |
| 3-4 servings/day | 0.95 | 0.56 to 1.60 | .83 | |
| 5 & over servings/day | 0.74 | 0.41 to 1.32 | .30 | |
| Vegetable consumption at baseline | 2406 | |||
| None | Ref. | |||
| 1-2 servings/day | 1.14 | 0.47 to 2.81 | .77 | |
| 3-4 servings/day | 0.86 | 0.35 to 2.12 | .75 | |
| 5 & over servings/day | 0.66 | 0.26 to 1.65 | .38 | |
| Fish consumption at baseline | 1921 | |||
| None | Ref. | |||
| 1 serving/week | 0.85 | 0.61 to 1.20 | .35 | |
| 2 servings/week | 0.71 | 0.52 to 0.99 | .04 | |
| 3 & more servings/week | 0.75 | 0.54 to 1.03 | .08 |
Supplementary Table S6.
Univariate analyses for hypertension at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 3020 | 0.98 | 0.97 to 0.99 | <.01 |
| Gender | 3020 | |||
| Female | Ref. | |||
| Male | 1.82 | 1.51 to 2.21 | <.01 | |
| BMI at baseline (kg/m2) | 3014 | |||
| Underweight | Ref. | |||
| Normal weight | 2.09 | 0.28 to 15.74 | .48 | |
| Overweight | 4.62 | 0.62 to 34.58 | .14 | |
| Obese | 6.66 | 0.89 to 49.89 | .07 | |
| Baseline abdominal obesity | 3007 | |||
| Non-obese | Ref. | |||
| Obese | 1.77 | 1.46 to 2.14 | <.01 | |
| Baseline 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.87 | 0.63 to 1.21 | .42 | |
| 75 to <100 | 0.59 | 0.42 to 0.83 | <.01 | |
| 100 to <125 | 0.62 | 0.43 to 0.89 | .01 | |
| ≥125 | 0.52 | 0.35 to 0.77 | <.01 | |
| Year 1 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.77 | 0.27 to 2.24 | .64 | |
| 75 to <100 | 0.61 | 0.22 to 1.75 | .36 | |
| 100 to <125 | 0.51 | 0.18 to 1.46 | .21 | |
| ≥125 | 0.47 | 0.17 to 1.34 | .16 | |
| Baseline AA:EPA | 2727 | 1.01 | 1.00 to 1.03 | .06 |
| Baseline vitamin B12 (pmol/L) | 3012 | |||
| <450 | Ref. | |||
| ≥450 | 0.92 | 0.76 to 1.11 | .36 | |
| Year 1 vitamin B12 (pmol/L) | 2997 | |||
| <450 | Ref. | |||
| ≥450 | 0.79 | 0.58 to 1.08 | .14 | |
| Past medical history | ||||
| No past medical history | Ref. | |||
| Hypertension | 3020 | 187.07 | 124.79 to 280.45 | <.01 |
| Heart disease | 3020 | 0.98 | 0.59 to 1.63 | .93 |
| Diabetes | 3020 | 0.66 | 0.39 to 1.14 | .14 |
| Past medication history | ||||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 3020 | 1.37 | 1.05 to 1.78 | .02 |
| Cardiac medication | 3020 | 1.74 | 1.26 to 2.41 | <.01 |
| Currently smoking at baseline | 2972 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.19 | 0.93 to 1.53 | .18 | |
| Alcohol consumption at baseline | 3019 | |||
| None | Ref. | |||
| Drinking in past year | 1.01 | 0.81 to 1.27 | .91 | |
| Physical activity at baseline | 472 | |||
| Mild | Ref. | |||
| Moderate | 1.18 | 0.70 to 2.01 | .53 | |
| Strenuous | 0.76 | 0.17 to 3.48 | .72 | |
| No physical activity | 1.20 | 0.54 to 2.66 | .66 | |
| Fruit consumption at baseline | 2469 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.14 | 0.60 to 2.15 | .69 | |
| 3 to 4 servings/day | 1.09 | 0.57 to 2.06 | .80 | |
| 5 & over servings/day | 0.67 | 0.32 to 1.39 | .28 | |
| Vegetable consumption at baseline | 2473 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.08 | 0.37 to 3.21 | .89 | |
| 3 to 4 servings/day | 0.99 | 0.33 to 2.92 | .98 | |
| 5 & over servings/day | 0.93 | 0.31 to 2.82 | .90 | |
| Fish consumption at baseline | 2005 | |||
| None | Ref. | |||
| 1 serving/week | 0.86 | 0.56 to 1.30 | .46 | |
| 2 servings/week | 1.14 | 0.78 to 1.67 | .51 | |
| 3 & more servings/week | 0.94 | 0.64 to 1.38 | .74 |
Supplementary Table S7.
Univariate analyses for hypertriglyceridemia at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 3020 | 0.99 | 0.98 to 1.00 | .02 |
| Gender | 3020 | |||
| Female | Ref. | |||
| Male | 1.21 | 1.03 to 1.44 | .02 | |
| BMI at baseline (kg/m2) | 3014 | |||
| Underweight | Ref. | |||
| Normal weight | 2.37 | 0.31 to 17.87 | .40 | |
| Overweight | 6.22 | 0.83 to 46.53 | .08 | |
| Obese | 12.33 | 1.65 to 92.32 | .01 | |
| Baseline abdominal obesity | 3007 | |||
| Non-obese | Ref. | |||
| Obese | 2.90 | 2.44 to 3.46 | <.01 | |
| Baseline 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.64 | 0.48 to 0.85 | <.01 | |
| 75 to <100 | 0.44 | 0.33 to 0.58 | <.01 | |
| 100 to <125 | 0.34 | 0.24 to 0.47 | <.01 | |
| ≥125 | 0.22 | 0.15 to 0.32 | <.01 | |
| Year 1 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 1.00 | 0.37 to 2.75 | .99 | |
| 75 to <100 | 0.72 | 0.27 to 1.95 | .52 | |
| 100 to <125 | 0.58 | 0.22 to 1.57 | .29 | |
| ≥125 | 0.48 | 0.18 to 1.28 | .14 | |
| Baseline AA:EPA | 2727 | 1.00 | 0.99 to 1.02 | .55 |
| Baseline vitamin B12 (pmol/L) | 3012 | |||
| <450 | Ref. | |||
| ≥450 | 0.73 | 0.62 to 0.87 | <.01 | |
| Year 1 vitamin B12 (pmol/L) | 2997 | |||
| <450 | Ref. | |||
| ≥450 | 0.87 | 0.66 to 1.16 | .35 | |
| Past medical history | 3020 | |||
| No past medical history | Ref. | |||
| Hypertension | 1.85 | 1.47 to 2.32 | <.01 | |
| Heart disease | 1.13 | 0.73 to 1.73 | .60 | |
| Diabetes | 1.58 | 1.08 to 2.32 | .02 | |
| Past medication history | 3020 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 1.27 | 0.99 to 1.61 | .06 | |
| Cardiac medication | 1.34 | 1.00 to 1.80 | .05 | |
| Currently smoking at baseline | 2972 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.14 | 0.91 to 1.43 | .27 | |
| Alcohol consumption at baseline | 3019 | |||
| None | Ref. | |||
| Drinking in past year | 1.01 | 0.83 to 1.24 | .92 | |
| Physical activity at baseline | 472 | |||
| Mild | Ref. | |||
| Moderate | 1.42 | 0.89 to 2.29 | .14 | |
| Strenuous | 0.58 | 0.13 to 2.63 | .48 | |
| No physical activity | 2.16 | 1.11 to 4.19 | .02 | |
| Fruit consumption at baseline | 2469 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.76 | 0.45 to 1.26 | .28 | |
| 3 to 4 servings/day | 0.69 | 0.41 to 1.15 | .16 | |
| 5 & over servings/day | 0.47 | 0.26 to 0.84 | .01 | |
| Vegetable consumption at baseline | 2473 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.82 | 0.34 to 2.01 | .67 | |
| 3 to 4 servings/day | 0.79 | 0.32 to 1.93 | .61 | |
| 5 & over servings/day | 0.56 | 0.23 to 1.40 | .22 | |
| Fish consumption at baseline | 2005 | |||
| None | Ref. | |||
| 1 serving/week | 0.97 | 0.67 to 1.41 | .89 | |
| 2 servings/week | 1.01 | 0.71 to 1.42 | .98 | |
| 3 & more servings/week | 1.00 | 0.71 to 1.42 | .99 |
Supplementary Table S8.
Univariate analyses for low high-density lipoprotein level at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 3020 | 1.01 | 1.00 to 1.02 | .20 |
| Gender | 3020 | |||
| Female | Ref. | |||
| Male | 0.65 | 0.53 to 0.79 | <.01 | |
| BMI at baseline (kg/m2) | 3014 | |||
| Underweight | Ref. | |||
| Normal weight | 1.83 | 0.24 to 13.85 | .56 | |
| Overweight | 3.69 | 0.49 to 27.68 | .20 | |
| Obese | 7.58 | 1.01 to 56.81 | .05 | |
| Baseline abdominal obesity | 3007 | |||
| Non-obese | Ref. | |||
| Obese | 3.63 | 2.95 to 4.47 | <.01 | |
| Baseline 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.65 | 0.47 to 0.90 | <.01 | |
| 75 to <100 | 0.52 | 0.38 to 0.72 | <.01 | |
| 100 to <125 | 0.48 | 0.34 to 0.69 | <.01 | |
| ≥125 | 0.43 | 0.29 to 0.63 | <.01 | |
| Year 1 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 1.14 | 0.36 to 3.56 | .83 | |
| 75 to <100 | 0.91 | 0.29 to 2.79 | .86 | |
| 100 to <125 | 0.63 | 0.20 to 1.94 | .42 | |
| ≥125 | 0.51 | 0.17 to 1.58 | .25 | |
| Baseline AA:EPA | 2727 | 1.01 | 1.00 to 1.03 | .04 |
| Baseline vitamin B12 (pmol/L) | 3012 | |||
| <450 | Ref. | |||
| ≥450 | 0.88 | 0.72 to 1.07 | .19 | |
| Year 1 vitamin B12 (pmol/L) | 2997 | |||
| <450 | Ref. | |||
| ≥450 | 0.85 | 0.62 to 1.17 | .32 | |
| Past medical history | 3020 | |||
| No past medical history | Ref. | |||
| Hypertension | 1.23 | 0.94 to 1.62 | .13 | |
| Heart disease | 1.94 | 1.28 to 2.96 | <.01 | |
| Diabetes | 1.58 | 1.05 to 2.39 | .03 | |
| Past medication history | 3020 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 1.83 | 1.42 to 2.36 | <.01 | |
| Cardiac medication | 1.84 | 1.35 to 2.50 | <.01 | |
| Currently smoking at baseline | 2972 | |||
| Non-smoker | ||||
| Smoker | 1.02 | 0.78 to 1.33 | .89 | |
| Alcohol consumption at baseline | 3019 | |||
| None | Ref. | |||
| Drinking in past year | 0.65 | 0.52 to 0.80 | <.01 | |
| Physical activity at baseline | 472 | |||
| Mild | Ref. | |||
| Moderate | 1.47 | 0.87 to 2.49 | .15 | |
| Strenuous | 0.39 | 0.05 to 3.04 | .37 | |
| No physical activity | 2.11 | 1.02 to 4.35 | .04 | |
| Fruit consumption at baseline | 2469 | |||
| None | Ref. | |||
| 1-2 servings/day | 0.85 | 0.47 to 1.55 | .60 | |
| 3-4 servings/day | 0.99 | 0.54 to 1.80 | .96 | |
| 5 & over servings/day | 0.67 | 0.34 to 1.32 | .25 | |
| Vegetable consumption at baseline | 2473 | |||
| None | Ref. | |||
| 1-2 servings/day | 0.60 | 0.23 to 1.53 | .29 | |
| 3-4 servings/day | 0.67 | 0.26 to 1.70 | .40 | |
| 5 & over servings/day | 0.48 | 0.18 to 1.25 | .13 | |
| Fish consumption at baseline | 2005 | |||
| None | Ref. | |||
| 1 serving/week | 1.11 | 0.74 to 1.68 | .62 | |
| 2 servings/week | 0.87 | 0.58 to 1.29 | .49 | |
| 3 & more servings/week | 0.99 | 0.67 to 1.47 | .97 |
Supplementary Table S9.
Univariate analyses for hyperglycemia at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 3020 | 1.03 | 1.02 to 1.04 | <.01 |
| Gender | 3020 | |||
| Female | Ref. | |||
| Male | 1.62 | 1.35 to 1.93 | <.01 | |
| BMI at baseline (kg/m2) | 3014 | |||
| Underweight | Ref. | |||
| Normal weight | 2.11 | 0.28 to 15.93 | .47 | |
| Overweight | 4.62 | 0.62 to 34.57 | .14 | |
| Obese | 10.36 | 1.38 to 77.60 | .02 | |
| Baseline abdominal obesity | 3007 | |||
| Non-obese | Ref. | |||
| Obese | 2.99 | 2.49 to 3.60 | <.01 | |
| Baseline 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.71 | 0.53 to 0.96 | .03 | |
| 75 to <100 | 0.56 | 0.41 to 0.76 | <.01 | |
| 100 to <125 | 0.38 | 0.27 to 0.54 | <.01 | |
| ≥125 | 0.33 | 0.23 to 0.49 | <.01 | |
| Year 1 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 1.74 | 0.49 to 6.16 | .39 | |
| 75 to <100 | 1.55 | 0.44 to 5.41 | .49 | |
| 100 to <125 | 1.25 | 0.36 to 4.37 | .73 | |
| ≥125 | 0.97 | 0.28 to 3.40 | .97 | |
| Baseline AA:EPA | 2727 | 1.02 | 1.00 to 1.03 | .01 |
| Baseline vitamin B12 (pmol/L) | 3012 | |||
| <450 | Ref. | |||
| ≥450 | 0.80 | 0.67 to 0.96 | .02 | |
| Year 1 vitamin B12 (pmol/L) | 2997 | |||
| <450 | Ref. | |||
| ≥450 | 0.81 | 0.60 to 1.09 | .17 | |
| Past medical history | 3020 | |||
| No past medical history | Ref. | |||
| Hypertension | 1.62 | 1.28 to 2.06 | <.01 | |
| Heart disease | 1.52 | 0.99 to 2.31 | .05 | |
| Diabetes | 10.44 | 7.05 to 15.46 | <.01 | |
| Past medication history | 3020 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 2.25 | 1.78 to 2.84 | <.01 | |
| Cardiac medication | 2.01 | 1.51 to 2.67 | <.01 | |
| Currently smoking at baseline | 2972 | |||
| Non-smoker | Ref. | |||
| Smoker | 0.95 | 0.74 to 1.22 | .71 | |
| Alcohol consumption at baseline | 3019 | |||
| None | Ref. | |||
| Drinking in past year | 0.94 | 0.76 to 1.16 | .54 | |
| Physical activity at baseline | 472 | |||
| Mild | Ref. | |||
| Moderate | 1.08 | 0.66 to 1.77 | .76 | |
| Strenuous | 1.32 | 0.41 to 4.26 | .64 | |
| No physical activity | 1.28 | 0.63 to 2.64 | .50 | |
| Fruit consumption at baseline | 2469 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.88 | 0.51 to 1.52 | .64 | |
| 3 to 4 servings/day | 0.77 | 0.44 to 1.34 | .36 | |
| 5 & over servings/day | 0.68 | 0.36 to 1.26 | .22 | |
| Vegetable consumption at baseline | 2473 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.17 | 0.43 to 3.18 | .75 | |
| 3 to 4 servings/day | 0.95 | 0.35 to 2.56 | .91 | |
| 5 & over servings/day | 0.75 | 0.27 to 2.06 | .57 | |
| Fish consumption at baseline | 2005 | |||
| None | Ref. | |||
| 1 serving/week | 1.40 | 0.94 to 2.09 | .10 | |
| 2 servings/week | 1.01 | 0.68 to 1.50 | .97 | |
| 3 & more servings/week | 1.20 | 0.81 to 1.76 | .36 |
Supplementary Table S10.
Univariate analyses for metabolic syndrome at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 3020 | 1.00 | 0.99 to 1.01 | .99 |
| Gender | 3020 | |||
| Female | Ref. | |||
| Male | 0.94 | 0.77 to 1.14 | .53 | |
| BMI at baseline (kg/m2) | 2993 | |||
| Underweight | Ref. | |||
| Normal weight | 0.03 | 0.02 to 0.05 | <.01 | |
| Overweight | 0.24 | 0.19 to 0.30 | <.01 | |
| Obese | ||||
| Baseline abdominal obesity | 3007 | |||
| Non-obese | Ref. | |||
| Obese | 12.03 | 9.12 to 15.87 | <.01 | |
| Baseline 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.62 | 0.46 to 0.84 | <.01 | |
| 75 to <100 | 0.35 | 0.25 to 0.48 | <.01 | |
| 100 to <125 | 0.28 | 0.20 to 0.41 | <.01 | |
| ≥125 | 0.23 | 0.15 to 0.35 | <.01 | |
| Year 1 25(OH)D (nmol/L) | 3020 | |||
| <50 | Ref. | |||
| 50 to <75 | 1.12 | 0.36 to 3.50 | .85 | |
| 75 to <100 | 0.90 | 0.29 to 2.77 | .85 | |
| 100 to <125 | 0.59 | 0.19 to 1.82 | .36 | |
| ≥125 | 0.48 | 0.16 to 1.47 | .20 | |
| Baseline AA:EPA | 2727 | 1.02 | 1.01 to 1.03 | <.01 |
| Baseline vitamin B12 (pmol/L) | 3012 | |||
| <450 | Ref. | |||
| ≥450 | 0.77 | 0.63 to 0.94 | <.01 | |
| Year 1 vitamin B12 (pmol/L) | 2997 | |||
| <450 | Ref. | |||
| ≥450 | 0.78 | 0.57 to 1.08 | .13 | |
| Past medical history | 3020 | |||
| No past medical history | Ref. | |||
| Hypertension | 4.66 | 3.70 to 5.87 | <.01 | |
| Heart disease | 1.65 | 1.05 to 2.57 | .02 | |
| Diabetes | 3.16 | 2.16 to 4.62 | <.01 | |
| Past medication history | 3020 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 1.83 | 1.41 to 2.36 | <.01 | |
| Cardiac medication | 2.05 | 1.49 to 2.81 | <.01 | |
| Currently smoking at baseline | 2972 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.11 | 0.86 to 1.45 | .41 | |
| Alcohol consumption at baseline | 3019 | |||
| None | Ref. | |||
| Drinking in past year | 0.86 | 0.69 to 1.08 | .20 | |
| Physical activity at baseline | 472 | |||
| Mild | Ref. | |||
| Moderate | 1.27 | 0.73 to 2.20 | .40 | |
| Strenuous | 0.42 | 0.05 to 3.24 | .40 | |
| No physical activity | 2.02 | 0.96 to 4.24 | .06 | |
| Fruit consumption at baseline | 2469 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.37 | 0.69 to 2.71 | .37 | |
| 3 to 4 servings/day | 1.25 | 0.63 to 2.49 | .53 | |
| 5 & over servings/day | 0.73 | 0.34 to 1.60 | .44 | |
| Vegetable consumption at baseline | 2473 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.61 | 0.24 to 1.57 | .31 | |
| 3 to 4 servings/day | 0.60 | 0.24 to 1.53 | .29 | |
| 5 & over servings/day | 0.41 | 0.16 to 1.07 | .07 | |
| Fish consumption at baseline | 2005 | |||
| None | Ref. | |||
| 1 serving/week | 1.00 | 0.66 to 1.51 | 1.00 | |
| 2 servings/week | 0.86 | 0.57 to 1.28 | .45 | |
| 3 & more servings/week | 0.83 | 0.56 to 1.23 | .36 |
Supplementary Table S11.
Univariate analyses for insulin resistance at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 2481 | 1.01 | 1.00 to 1.02 | .12 |
| Gender | 2481 | |||
| Female | Ref. | |||
| Male | 1.50 | 1.23 to 1.82 | <.01 | |
| BMI at baseline (kg/m2) | 2470 | |||
| Underweight | Ref. | |||
| Normal weight | 0.06 | 0.04 to 0.10 | <.01 | |
| Overweight | 0.23 | 0.19 to 0.29 | <.01 | |
| Obese | ||||
| Abdominal obesity at baseline | 2468 | |||
| Non-obese | Ref. | |||
| Obese | 6.02 | 4.72 to 7.68 | <.01 | |
| 25(OH)D at baseline (nmol/L) | 2481 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.62 | 0.45 to 0.85 | <.01 | |
| 75 to <100 | 0.39 | 0.28 to 0.54 | <.01 | |
| 100 to <125 | 0.29 | 0.20 to 0.42 | <.01 | |
| ≥125 | 0.27 | 0.18 to 0.41 | <.01 | |
| 25(OH)D at Year 1 (nmol/L) | 2481 | |||
| <50 | Ref. | |||
| 50 to <75 | 1.26 | 0.40 to 3.98 | .70 | |
| 75 to <100 | 1.00 | 0.32 to 3.12 | 1.00 | |
| 100 to <125 | 0.74 | 0.24 to 2.31 | .61 | |
| ≥125 | 0.61 | 0.19 to 1.89 | .39 | |
| Baseline AA:EPA | 2230 | 1.03 | 1.02 to 1.05 | <.01 |
| Baseline vitamin B12 (pmol/L) | 2475 | |||
| <450 | Ref. | |||
| ≥450 | 0.85 | 0.70 to 1.04 | .12 | |
| Year 1 vitamin B12 (pmol/L) | 2462 | |||
| <450 | Ref. | |||
| ≥450 | 0.67 | 0.49 to 0.91 | .01 | |
| Past medical history | 2481 | |||
| No past medical history | Ref. | |||
| Hypertension | 2.03 | 1.58 to 2.60 | <.01 | |
| Heart disease | 1.22 | 0.76 to 1.95 | .41 | |
| Diabetes | 4.78 | 3.18 to 7.17 | <.01 | |
| Past medication history | 2481 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 1.88 | 1.45 to 2.44 | <.01 | |
| Cardiac medication | 1.99 | 1.44 to 2.73 | <.01 | |
| Currently smoking at baseline | 2439 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.16 | 0.89 to 1.51 | .28 | |
| Alcohol consumption at baseline | 2480 | |||
| None | Ref. | |||
| Drinking in past year | 0.76 | 0.61 to 0.96 | .02 | |
| Physical activity at baseline | 362 | |||
| Mild | Ref. | |||
| Moderate | 0.84 | 0.46 to 1.52 | .56 | |
| Strenuous | ||||
| No physical activity | 1.30 | 0.61 to 2.79 | .50 | |
| Fruit consumption at baseline | 2034 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.09 | 0.58 to 2.03 | .79 | |
| 3 to 4 servings/day | 0.93 | 0.49 to 1.75 | .82 | |
| 5 & over servings/day | 0.68 | 0.33 to 1.39 | .29 | |
| Vegetable consumption at baseline | 2037 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.76 | 0.29 to 1.99 | .58 | |
| 3 to 4 servings/day | 0.57 | .26 | ||
| 5 & over servings/day | 0.38 | 0.14 to 1.03 | .06 | |
| Fish consumption at baseline | 1652 | |||
| None | Ref. | |||
| 1 serving/week | 0.84 | 0.56 to 1.26 | .40 | |
| 2 servings/week | 0.56 | 0.37 to 0.83 | <.01 | |
| 3 & more servings/week | 0.67 | 0.45 to 0.99 | .04 |
Supplementary Table S12.
Univariate analyses for diabetes at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 3013 | 1.03 | 1.02 to 1.05 | <.01 |
| Gender | 3013 | |||
| Female | Ref. | |||
| Male | 1.73 | 1.26 to 2.36 | <.01 | |
| BMI at baseline (kg/m2) | 2986 | |||
| Underweight | Ref. | |||
| Normal weight | 0.22 | 0.14 to 0.35 | <.01 | |
| Overweight | 0.45 | 0.32 to 0.63 | <.01 | |
| Obese | ||||
| Abdominal obesity at baseline | 3000 | |||
| Non-obese | Ref. | |||
| Obese | 2.75 | 1.99 to 3.81 | <.01 | |
| 25(OH)D at baseline (nmol/L) | 3013 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.48 | 0.31 to 0.74 | <.01 | |
| 75 to <100 | 0.32 | 0.21 to 0.51 | <.01 | |
| 100 to <125 | 0.21 | 0.11 to 0.36 | <.01 | |
| ≥125 | 0.25 | 0.14 to 0.45 | <.01 | |
| 25(OH)D at Year 1 (nmol/L) | 2995 | |||
| <50 | Ref. | |||
| 50 to <75 | 2.25 | 1.36 to 3.72 | <.01 | |
| 75 to <100 | 2.35 | 1.58 to 3.51 | <.01 | |
| 100 to <125 | 1.04 | 0.66 to 1.63 | .86 | |
| ≥125 | ||||
| Baseline AA:EPA | 2720 | 1.03 | 1.01 to 1.05 | <.01 |
| Baseline vitamin B12 (pmol/L) | 3005 | |||
| <450 | Ref. | |||
| ≥450 | 0.66 | 0.48 to 0.91 | .01 | |
| Year 1 vitamin B12 (pmol/L) | 2990 | |||
| <450 | ||||
| ≥450 | 0.48 | 0.31 to 074 | .01 | |
| Past medical history | 3013 | |||
| No past medical history | Ref. | |||
| Hypertension | 1.12 | 0.73 to 1.74 | .60 | |
| Heart disease | 2.35 | 1.31 to 4.05 | <.01 | |
| Diabetes | 27.28 | 17.75 to 41.92 | <.01 | |
| Past medication history | 3013 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 2.99 | 2.10 to 4.24 | <.01 | |
| Cardiac medication | 2.39 | 1.57 to 3.65 | <.01 | |
| Currently smoking at baseline | 2965 | |||
| Non-smoker | Ref. | |||
| Smoker | 0.90 | 0.58 to 1.40 | .64 | |
| Alcohol consumption at baseline | 3012 | |||
| None | Ref. | |||
| Drinking in past year | 0.65 | 0.46 to 0.90 | .01 | |
| Physical activity at baseline | 454 | |||
| Mild | Ref. | |||
| Moderate | 0.99 | 0.47 to 2.08 | .97 | |
| Strenuous | ||||
| No physical activity | 0.49 | 0.11 to 2.18 | .35 | |
| Fruit consumption at baseline | 2465 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.39 | 0.43 to 4.53 | .59 | |
| 3 to 4 servings/day | 1.51 | 0.46 to 4.94 | .50 | |
| 5 & over servings/day | 1.18 | 0.32 to 4.30 | .80 | |
| Vegetable consumption at baseline | 2469 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.80 | 0.18 to 3.46 | .76 | |
| 3 to 4 servings/day | 0.62 | 0.14 to 2.71 | .53 | |
| 5 & over servings/day | 0.46 | 0.10 to 2.10 | .32 | |
| Fish consumption at baseline | 2001 | |||
| None | Ref. | |||
| 1 serving/week | 1.78 | 0.79 to 3.99 | .16 | |
| 2 servings/week | 1.34 | 0.60 to 3.00 | .47 | |
| 3 servings/week | 1.50 | 0.68 to 3.29 | .31 |
Supplementary Table S13.
Univariate analyses for hypercalcemia at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 3009 | 1.09 | 1.08 to 1.10 | <.01 |
| Gender | 3009 | |||
| Female | Ref. | |||
| Male | 13.48 | 10.53 to 17.27 | <.01 | |
| BMI at baseline (kg/m2) | 2982 | |||
| Underweight | Ref. | |||
| Normal weight | 0.34 | 0.26 to 0.43 | <.01 | |
| Overweight | 0.87 | 0.71 to 1.05 | .15 | |
| Obese | ||||
| Abdominal obesity at baseline | 2996 | |||
| Non-obese | Ref. | |||
| Obese | 1.30 | 1.10 to 1.54 | <.01 | |
| 25(OH)D at baseline (nmol/L) | 3009 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.78 | 0.58 to 1.05 | .10 | |
| 75 to <100 | 0.59 | 0.44 to 0.80 | <.01 | |
| 100 to <125 | 0.52 | 0.37 to 0.73 | <.01 | |
| ≥125 | 0.41 | 0.29 to 0.60 | <.01 | |
| 25(OH)D at Year 1 (nmol/L) | 3009 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.67 | 0.24 to 1.85 | .44 | |
| 75 to <100 | 0.61 | 0.23 to 1.64 | .33 | |
| 100 to <125 | 0.58 | 0.21 to 1.56 | .28 | |
| ≥125 | 0.51 | 0.19 to 1.38 | .19 | |
| Baseline AA:EPA | 2716 | 1.02 | 1.01 to 1.04 | <.01 |
| Baseline vitamin B12 (pmol/L) | 3001 | |||
| <450 | Ref. | |||
| ≥450 | 0.68 | 0.57 to 0.81 | <.01 | |
| Year 1 vitamin B12 (pmol/L) | 2986 | |||
| <450 | Ref. | |||
| ≥450 | 0.81 | 0.61 to 1.08 | .15 | |
| Past medical history | 3009 | |||
| No past medical history | Ref. | |||
| Hypertension | 2.86 | 2.29 to 3.57 | <.01 | |
| Heart disease | 2.06 | 1.38 to 3.06 | <.01 | |
| Diabetes | 2.73 | 1.90 to 3.94 | <.01 | |
| Past medication history | 3009 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 2.63 | 2.09 to 3.29 | <.01 | |
| Cardiac medication | 3.45 | 2.60 to 4.58 | <.01 | |
| Currently smoking at baseline | 2961 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.40 | 1.12 to 1.75 | <.01 | |
| Alcohol consumption at baseline | 3008 | |||
| None | Ref. | |||
| Drinking in past year | 1.03 | 0.84 to 1.27 | .79 | |
| Physical activity at baseline | 471 | |||
| Mild | Ref. | |||
| Moderate | 0.94 | 0.59 to 1.50 | .80 | |
| Strenuous | 0.42 | 0.09 to 1.91 | .26 | |
| No physical activity | 0.85 | 0.41 to 1.77 | .67 | |
| Fruit consumption at baseline | 2460 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.75 | 0.45 to 1.24 | .26 | |
| 3 to 4 servings/day | 0.63 | 0.38 to 1.06 | .08 | |
| 5 & over servings/day | 0.48 | 0.27 to 0.86 | .01 | |
| Vegetable consumption at baseline | 2464 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.17 | 0.46 to 2.99 | .74 | |
| 3 to 4 servings/day | 0.82 | 0.32 to 2.08 | .67 | |
| 5 & over servings/day | 0.60 | 0.23 to 1.57 | .30 | |
| Fish consumption at baseline | 1998 | |||
| None | Ref. | |||
| 1 serving/week | 0.97 | 0.66 to 1.40 | .86 | |
| 2 servings/week | 0.93 | 0.65 to 1.33 | .70 | |
| 3 & more servings/week | 0.93 | 0.65 to 1.32 | .68 |
Supplementary Table S14.
Univariate analyses for Reynold’s risk score at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 2918 | 1.17 | 1.16 to 1.19 | <.01 |
| Gender | 2918 | |||
| Female | Ref. | |||
| Male | 4.97 | 4.07 to 6.08 | <.01 | |
| BMI at baseline (kg/m2) | 2912 | |||
| Underweight | ||||
| Normal weight | 2.72 | 0.36 to 20.49 | .33 | |
| Overweight | 6.87 | 0.92 to 51.45 | .06 | |
| Obese | 7.19 | 0.96 to 53.91 | .06 | |
| Abdominal obesity at baseline | 2905 | |||
| Non-obese | Ref. | |||
| Obese | 1.39 | 1.16 to 1.66 | <.01 | |
| 25(OH)D at baseline (nmol/L) | 2918 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.91 | 0.66 to 1.26 | .58 | |
| 75 to 100 | 0.89 | 0.64 to 1.22 | .46 | |
| 100 to 125 | 0.75 | 0.53 to 1.07 | .11 | |
| ≥125 | 0.63 | 0.43 to 0.93 | .02 | |
| 25(OH)D at Year 1 (nmol/L) | 2918 | |||
| <50 | Ref. | |||
| 50 to 75 | 0.88 | 0.28 to 2.78 | .83 | |
| 75 to 100 | 0.94 | 0.31 to 2.90 | .92 | |
| 100 to 125 | 0.96 | 0.31 to 2.96 | .95 | |
| ≥125 | 0.97 | 0.31 to 2.96 | .95 | |
| Baseline AA:EPA | 2632 | 1.01 | 1.00 to .02 | .10 |
| Baseline vitamin B12 (pmol/L) | 2910 | |||
| <450 | Ref. | |||
| ≥450 | 0.76 | 0.64 to 0.91 | <.01 | |
| Year 1 vitamin B12 (pmol/L) | 2896 | |||
| <450 | Ref. | |||
| ≥450 | 1.04 | 0.76 to 1.43 | .79 | |
| Past medical history | 2918 | |||
| No past medical history | Ref. | |||
| Hypertension | 2.13 | 1.69 to 2.69 | <.01 | |
| Heart disease | 1.72 | 1.13 to 2.63 | .01 | |
| Diabetes | 3.39 | 2.33 to 4.92 | <.01 | |
| Past medication history | 2918 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 2.54 | 2.01 to 3.22 | <.01 | |
| Cardiac medication | 2.86 | 2.14 to 3.84 | <.01 | |
| Currently smoking at baseline | 2874 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.00 | 0.79 to 1.26 | .98 | |
| Alcohol consumption at baseline | 2917 | |||
| None | Ref. | |||
| Drinking in past year | 0.97 | 0.78 to 1.20 | .78 | |
| Physical activity at baseline | 455 | |||
| Mild | Ref. | |||
| Moderate | 0.82 | 0.51 to 1.31 | .40 | |
| Strenuous | 0.36 | 0.08 to 1.65 | .19 | |
| No physical activity | 0.71 | 0.33 to 1.51 | .37 | |
| Fruit consumption at baseline | 2394 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.88 | 0.52 to 1.52 | .66 | |
| 3 to 4 servings/day | 0.83 | 0.48 to 1.42 | .49 | |
| 5 & over servings/day | 0.63 | 0.34 to 1.17 | .15 | |
| Vegetable consumption at baseline | 2396 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.33 | 0.49 to 3.62 | .58 | |
| 3 to 4 servings/day | 0.98 | 0.36 to 2.68 | .97 | |
| 5 & over servings/day | 0.77 | 0.28 to 2.14 | .62 | |
| Fish consumption at baseline | 1951 | |||
| None | Ref. | |||
| 1 serving/week | 0.96 | 0.65 to 1.43 | .85 | |
| 2 servings/week | 1.08 | 0.75 to 1.57 | .67 | |
| 3 & more servings/week | 1.06 | 0.73 to 1.53 | .76 |
Supplementary Table S15.
Univariate analyses for inflammation at follow-up, roughly one year.
| N | Univariate OR | 95% CI | P Value | |
|---|---|---|---|---|
| Age | 2989 | 1.01 | 1.00 to 1.02 | .09 |
| Gender | 2989 | |||
| Female | Ref. | |||
| Male | 0.77 | 0.64 to 0.92 | <.01 | |
| BMI at baseline (kg/m2) | 2983 | |||
| Underweight | Ref. | |||
| Normal weight | 0.98 | 0.22 to 4.26 | .97 | |
| Overweight | 2.03 | 0.47 to 8.80 | .34 | |
| Obese | 5.52 | 1.28 to 23.85 | .02 | |
| Abdominal obesity at baseline | 2976 | |||
| Non-obese | Ref. | |||
| Obese | 3.46 | 2.87 to 4.18 | <.01 | |
| 25(OH)D at baseline (nmol/L) | 2989 | |||
| <50 | Ref. | |||
| 50 to <75 | 0.60 | 0.44 to 0.81 | <.01 | |
| 75 to <100 | 0.54 | 0.40 to 0.72 | <.01 | |
| 100 to <125 | 0.35 | 0.25 to 0.49 | <.01 | |
| ≥125 | 0.37 | 0.26 to 0.54 | <.01 | |
| 25(OH)D at Year 1 (nmol/L) | 2989 | |||
| <50 | Ref. | |||
| 50 to <75 | 2.42 | 0.68 to 8.54 | .17 | |
| 75 to <100 | 1.48 | 0.42 to 5.18 | .54 | |
| 100 to <125 | 1.18 | 0.34 to 4.13 | .79 | |
| ≥125 | 0.98 | 0.28 to 3.41 | .97 | |
| Baseline AA:EPA | 2697 | 1.02 | 1.00 to 1.03 | <.01 |
| Baseline vitamin B12 (pmol/L) | 2981 | |||
| <450 | Ref. | |||
| ≥450 | 0.77 | 0.65 to 0.93 | .01 | |
| Year 1 vitamin B12 (pmol/L) | 2966 | |||
| <450 | Ref. | |||
| ≥450 | 0.76 | 0.57 to 1.02 | .07 | |
| Past medical history | 2989 | |||
| No past medical history | Ref. | |||
| Hypertension | 1.27 | 0.99 to 1.63 | .06 | |
| Heart disease | 0.76 | 0.46 to 1.25 | .28 | |
| Diabetes | 1.34 | 0.89 to 2.01 | .16 | |
| Past medication history | 2989 | |||
| No past medication history | Ref. | |||
| Blood pressuring-lowering med. | 1.62 | 1.27 to 2.07 | <.01 | |
| Cardiac medication | 1.30 | 0.96 to 1.75 | .09 | |
| Currently smoking at baseline | 2942 | |||
| Non-smoker | Ref. | |||
| Smoker | 1.28 | 1.01 to 1.62 | .04 | |
| Alcohol consumption at baseline | 2988 | |||
| None | Ref. | |||
| Drinking in past year | 0.86 | 0.70 to 1.06 | .15 | |
| Physical activity at baseline | 467 | |||
| Mild | Ref. | |||
| Moderate | 0.53 | 0.32 to 0.89 | .02 | |
| Strenuous | 0.40 | 0.09 to 1.81 | .23 | |
| No physical activity | 2.10 | 1.12 to 3.95 | .02 | |
| Fruit consumption at baseline | 2445 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 0.55 | 0.33 to 0.92 | .02 | |
| 3 to 4 servings/day | 0.50 | 0.30 to 0.84 | .01 | |
| 5 & over servings/day | 0.51 | 0.28 to 0.90 | .02 | |
| Vegetable consumption at baseline | 2448 | |||
| None | Ref. | |||
| 1 to 2 servings/day | 1.04 | 0.39 to 2.83 | .93 | |
| 3 to 4 servings/day | 0.96 | 0.35 to 2.59 | .93 | |
| 5 & over servings/day | 0.88 | 0.32 to 2.42 | .80 | |
| Fish consumption at baseline | 1987 | |||
| None | Ref. | |||
| 1 serving/week | 0.80 | 0.54 to 1.19 | .27 | |
| 2 servings/week | 1.00 | 0.70 to 1.44 | 1.00 | |
| 3 servings/week | 0.78 | 0.54 to 1.12 | .18 |
Although correlation analyses recovered some association between vitamin B12 and CVD risk parameters (Table 4), regression analyses adjusted for covariates suggested that elevated vitamin B12 levels are not strongly associated with reductions in any of the CVD risk parameters (Table 6). Older age and/or male gender, and greater BMI were significant parameters that predicted abdominal obesity, hypertension, hypertriglyceridemia, low HDL, elevated FBG, insulin resistance, diabetes, inflammation, and elevated Framingham and Reynolds risk scores.
Discussion
The Pure North program focuses on overall wellness to reduce risk factors and prevent chronic disease, including cardiovascular disease, through lifestyle advice and nutrient supplementation, particularly optimization of vitamin D. A comparison of biomarkers between baseline and follow-up found that while some markers improved (such as mean HbA1c, fasting insulin and DBP), others worsened (such as mean TG, HDL and LDL) (Table 2). The prevalence of CVD risk factors was significantly reduced after one year in the program for a significant proportion of participants, with a small portion of participants that went on to develop risk factors (Table 3). Overall, the results indicate a favorable effect on CVD risk associated with the intervention, optimized vitamin D status (serum 25(OH)D ≥100 nmol/L), and improved nutrition.
Without a control group it is difficult to attribute improved health outcomes to any specific program component; yet, the consistency of these relationships with serum 25(OH)D concentrations suggests that achieving optimal vitamin D status may have been a contributing factor. Even after adjustments for age, gender, BMI, BP, AA:EPA, vitamin B12, presence of inflammation, tobacco use, and fruit consumption, serum 25(OH)D concentrations ≥100 nmol/L were significantly associated with reductions in most of the CVD risk parameters (Table 6). We observed higher rates of CVD riskfactors in the Pure North population in comparison with CHMS31-32 data which may indicate awareness and that participants of the Pure North program have sought natural ways to mitigate disease they know they are at risk of developing due to the presence of those risk factors.
Vitamin D deficiency is closely tied to the onset of CVD and is suggested to predispose individuals to CVD risk parameters.34-37 Although the precise mechanisms through which vitamin D may protect against CVD and the associated risk parameters remains somewhat uncertain, several pathways have been proposed.12,38-39 For example, the effects of vitamin D on tissue remodeling could limit cardiac hypertrophy, and the calcification and proliferation of smooth muscle tissue.39 Vitamin D is an immunomodulatory and anti-inflammatory agent and may initiate changes in the inflammatory cascade to prevent plaque and thrombosis formation, and down-regulation of the renin-angiotensin-aldosterone system to lower blood pressure and prevent hypertension.38,40 Vitamin D may additionally promote pancreatic secretion of insulin and improve glucose tolerance, and suppress the effect of parathyroid hormone.41,42
Of course, nutrients are not consumed in isolation. Studying the effects of single nutrients on CVD risk parameters without considering the interactions between nutrients could conceal or limit outcomes. For example, after one year of treatment in the Pure North program, more than 90% of participants reached serum vitamin B12 concentrations above 450 pmol/L. Regression models found vitamin B12 concentrations were associated with approximately half of the CVD risk parameters; AA:EPA concentrations were associated with the CVD risk parameters but with half the effects and in the opposing direction of expected. To study the effects of single nutrients, Heaney5 recommended that the nutritional status of all potentially related nutrients be optimized due to the dependence of enzymatic function on nutrients in all metabolic pathways and the interconnectedness of each step in and between pathways. Optimizing all other nutrients thus permits the fair evaluation of the nutrient of interest. However, the “optimal” level of each nutrient may differ based on disease status of the individual; be relative to the status of the other nutrients; or it may not be established for the condition of interest as recommended nutrient levels are targeted at preventing the disease that results from that nutrients deficiency, not on achieving optimal levels. The Pure North program includes a broad range of nutritional supplements including a multivitamin/multimineral formula, additional vitamins D3, B12, and omega-3 fatty acids and individualized consultations for lifestyle modifications (e.g., diet, physical activity). Therefore, although many of the analyses conducted in this study accentuate the benefits of optimal vitamin D status, it is likely that numerous other nutrients supplied were necessary for vitamin D to have a measurable effect on CVD risk parameters. Lifestyle modifications may also be necessary.
Our results are in line with the vast number of published cross-sectional and observational studies which showed an inverse association between 25(OH)D concentrations and CVD risks.8,11,43,44 In a meta-analysis of 22 prospective observational studies, for instance, Wang et al.45 demonstrated a nearly linear, inverse association between 25(OH)D concentrations and risk of CVD. Unfortunately, only a few randomized clinical trials specifically designed to assess the effects of vitamin D on CVD risk parameters have been performed, providing somewhat conflicting results.46-49 The Women’s Health Initiative (WHI) Calcium-Vitamin D trial reported little to no reduction in CVD risk with combined calcium and vitamin D supplementation.46,50 Yet, it should be noted that the median baseline 25(OH)D for participants within the WHI trial was approximately 42 nmol/L and, based on dosage used and compliance, the effect of supplementation would have been an increase of just 5 nmol/L-less than half the target achieved in the current study. Zaleski et al.51 found significant differences among participants of the DAYLIGHT trial taking high-doses (4000 IU/d) in comparison with low-doses (400 IU/d) of vitamin D over six months on surrogates of systemic arterial stiffness. In accordance with this latter study, our results suggest that a daily vitamin D3 dose of at least 4000 IU/d and a 25(OH)D concentration above 100 nmol/L may be required to improve CVD outcomes.
We observed large reductions in the prevalence of CVD risk parameters between baseline and follow-up (Table 3). Of those who were prediabetic at baseline, half (56.3%) were within the reference range at follow-up. For those with a high Reynold’s risk score at baseline, a quarter (24.1%) were no longer at high risk. While not all mean values improved (for example FBG, LDL and TG increased), values were within the reference range at follow-up, thus not directly corresponding to presence of a risk factor. What is remarkable is that the proportion of participants that went on to develop risk parameters was under 10% for most risk parameters and under 2% developed diabetes.
It is also noteworthy that a prevention program such as this may provide economic advantage in addition to improved health outcomes. The average annual cost of a course of prescription medication for CVD (including a generic statin, beta blocker, and ACE inhibitor) in Canada was $1 312 in 2016.33 In comparison, an average Pure North program costs $1 068 annually. With further potential beneficial impacts on quality of life, inflammatory and chronic disease outcomes, on top of reduced CVD risk factors. Such a community-based preventive health and wellness program is a potentially cost-effective and scalable method that should be explored prospectively.
The results from this study offer an analysis of a real-life, community-based program, but there are several limitations. Although covariates such as age, gender, and prescribed medications have been controlled, other residual variables cannot be ruled out; this study does not equate to a randomized controlled trial. Because participants volunteer to be in the program and we have relied on follow-up visits to assess these outcomes, a selection bias is likely. Despite these limitations, with over 3000 participants included, this study is one of the largest yet to assess the impact of a health and wellness program on CVD risk parameters over time. Western medicine and its gold standard, the RCT, take a reductionist approach to health, whereas the present study is of an integrative program that provides advice and guidance for a true lifestyle intervention. This assessment offers data for multiple outcomes in patients that would likely not fit the strict inclusion criteria of many RCTs. Further, participants in RCTs often use supplements and pharmaceuticals that are not captured and included in the analysis. For example, taking aspirin for a headache or magnesium for muscle cramps may be common but are often not asked about specifically or reported by the patient even when prompted. As such, this study provides insight into realistic outcomes that can be expected as part of an individualized health and wellness program.
Conclusions
In this large, retrospective study, we observed that participants of a health and wellness program tended to demonstrate improvements in CVD risk parameters at follow-up. In the context of the program, achieving optimal 25(OH)D concentrations (≥100 nmol/L) was associated with significant reductions in CVD risk parameters. Mean Framingham and Reynold’s risk scores were also reduced after one year in the program and participants in high risk categories had reductions that translated to lower risk for CVD. Overall, preventive health and wellness programs offer a scalable and effective option for reducing the prevalence of CVD risk parameters and therefore CVD. Inflammation, insulin resistance, and type 2 diabetes mellitus are also risk parameters for diseases beyond CVD, including dementia and cancer, suggesting that other health benefits may be afforded by such a program.
Supplementary Material
Additional supplementary tables can be found at http://imjournal.com/kimball
Footnotes
Funding
There was no funding provided directly for this work. Salaried employees of Pure North S’Energy Foundation, a not for profit organization, designed the study, performed data analyses, and wrote the manuscript, all in collaboration with Dr. Mimi Guarneri.
Conflict of Interest
None.
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