Abstract
BACKGROUND
Higher dietary phosphorus is associated with left ventricular hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For this reason, we hypothesized that dietary phosphorus may be associated with adverse clinic and ambulatory BP patterns.
METHODS
Our study included 973 African American adults enrolled in the Jackson Heart Study (2000–2004) with 24-hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary phosphorus from a validated Food Frequency Questionnaire as follows: (i) absolute daily intake, (ii) ratio of phosphorus-to-protein intake, (iii) phosphorus density, and (iv) energy-adjusted phosphorus intake. Using multivariable linear regression, we determined associations between dietary phosphorus intake and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure in clinic and over daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping was also assessed. Using logistic regression, we modeled relationships between dietary phosphorus intake and clinically relevant qualitative BP phenotypes, such as masked, sustained, or white-coat hypertension and normotension.
RESULTS
There were no statistically significant associations between phosphorus intake and SBP or pulse pressure in adjusted models. Most metrics of higher phosphorus intake were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus intake was not associated with clinic or ABPM-defined hypertension overall, but most metrics of higher phosphorus intake were associated with lower odds of sustained hypertension compared to sustained normotension, white-coat hypertension, and masked hypertension. There were no associations between dietary phosphorus and nocturnal BP dipping.
CONCLUSIONS
These data do not support a role for higher phosphorus intake and higher BP in African Americans.
Keywords: African American, ambulatory blood pressure, blood pressure, chronic kidney disease, diet, hypertension, nutrition, phosphorus
Hypertension is an increasingly common health condition that disproportionately affects African Americans.1 The prevention of high blood pressure (BP) can substantially lower global cardiovascular disease, making risk factor studies a high impact area.2 Recent expert working groups have highlighted opportunities to study risk factors for hypertension in African Americans using the rich data available through the Jackson Heart Study (JHS), a population-based cohort of African Americans in the greater Jackson, Mississippi area.3 In addition to other questions, determining the association between nutrients and BP was identified as an important research opportunity.3 In this study, we evaluated the role of excess dietary phosphorus as a risk factor for hypertension and abnormal clinic and ambulatory BP patterns in African Americans using data from the JHS.
Excess dietary phosphorus is a growing public health concern due to overall increases in dietary phosphorus intake at the population level4 and well-described links between deranged phosphorus homeostasis and adverse cardiovascular outcomes.5–7 Specifically, high intake of phosphorus, particularly from highly absorbable sources such as phosphorus-based food additives, may lead to abnormalities in the phosphorus axis, including high concentrations of serum phosphorus and the phosphorus regulatory hormone fibroblast growth factor 23.8–11 In animal models, phosphorus loading has been shown to increase BP and promote endothelial dysfunction.12,13 Short-term physiologic studies in humans also support a role of phosphorus loading in altered vascular function,13 and some observational studies suggest that high dietary phosphorus intake may associate with adverse outcomes, such as left ventricular hypertrophy and mortality.14,15 Due to the strong association of BP with these outcomes, we hypothesized that high dietary phosphorus intake may contribute to higher BP levels.
METHODS
Study population
We conducted a cross-sectional study using data from the JHS at baseline. Between 2000 and 2004, the JHS enrolled 5,306 African Americans, aged 20−95 years, from the Jackson, Mississippi Tri-County area. Our study focused on 973 participants with adequate measures of dietary intake and a complete 24-hour ambulatory blood pressure monitoring (ABPM) recording at the baseline visit.16 The JHS was approved by institutional review boards at the University of Mississippi Medical Center, Jackson State University, and Tougaloo College. All participants provided written informed consent.
Data collection
Our primary exposure was dietary phosphorus, assessed from a regionally appropriate Food Frequency Questionnaire (FFQ).17 Primary outcomes were mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), mean pulse pressure defined as the difference between mean SBP and mean DBP, and BP phenotypes determined from clinic BP measures and a 24-hour ABPM recording.16
Exposure measures
The JHS collected dietary intake using a shortened version of the Delta Nutrition Intervention Research Initiative FFQ, specifically designed to capture the typical diets and regional food consumption patterns of the Lower Mississippi Delta region. The Delta Nutrition Intervention Research Initiative FFQ has been validated against 24-hour recall interviews and nutrient biomarkers in the JHS.17,18 The short form of this FFQ querying 158 food items was used in the full JHS cohort. Participants with extreme energy intakes (≤600 or ≥4,800 kcal/day) were excluded.19 Total dietary phosphorus and other nutrients were derived from the Nutrition Data System for Research software developed by the Nutrition Coordinating Center, University of Minnesota, Minneapolis, Minnesota. Phosphorus is common in dairy and meat products, but it is also present in increasing quantities as a food additive.4,20 To better isolate variation in nonprotein phosphorus, we calculated the ratio of phosphorus-to-protein intake as an additional metric. To account for the correlation between phosphorus and energy intake, we evaluated phosphorus density, as the ratio of phosphorus-to-total energy, and energy-adjusted phosphorus intake, as the residual from the linear regression of phosphorus on total energy added to the phosphorus intake value at the mean energy intake.21
Outcome measures
Clinic BP was measured 2 times 1-minute apart using a random-zero sphygmomanometer calibrated to a semiautomatic oscillometric device, as described previously.22 The two BP measurements were averaged for analysis. Overall, 1,148 JHS participants underwent 24-hour ABPM using a commercial device (SpaceLabs 90207) on the nondominant arm, with BP recorded every 20 minutes.16 Data were evaluated for quality and a complete ABPM recording was defined using the International Database on Ambulatory Blood Pressure in relation to Cardiovascular Outcomes (IDACO) criteria. Specifically, participants were required to have ≥10 daytime (10 am to 8 pm) and ≥5 nighttime (midnight to 6 am) SBP and DBP measurements to be included in this analysis.23 Daytime and nighttime periods exclude sleep and wake transitions.24 All BP measurements from the ABPM were used to determine 24-hour SBP, DBP, and pulse pressure.
Nocturnal BP dipping was calculated as the percent difference between mean daytime and nighttime SBP and classified as dipper (≥10%) or nondipper (<10%).25 We used hypertension definitions from the 2013 European Society of Hypertension classifications for qualitative BP phenotypes,26 and defined clinic hypertension as clinic SBP ≥140 or DBP ≥90 mm Hg; 24-hour hypertension as mean 24-hour SBP ≥130 or DBP ≥80 mm Hg; and sustained hypertension as the presence of both clinic and 24-hour hypertension. White-coat hypertension was defined as clinic hypertension without 24-hour hypertension, and masked hypertension as the presence of 24-hour hypertension without clinic hypertension.27
Covariates
We calculated estimated glomerular filtration rate (eGFR) using the CKD-EPI equation for serum creatinine.28 Demographic features and medical history were obtained by self-report and physical examination. Diabetes mellitus was based on hemoglobin A1c ≥6.5% or a fasting glucose ≥126 mg/dl, or use of hypoglycemic medications or insulin, or self-reported diabetes. Current cigarette smoking status and current alcohol consumption were determined by self-report on questionnaires. Use of antihypertensive medication classes within the previous 2 weeks was ascertained by self-report and by review of pill bottles and prescriptions.29 Classes of antihypertensive medications considered included β-blockers, calcium channel blockers, diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, aldosterone antagonists, α-blockers, centrally acting agonists, and vasodilators.
Statistical analysis
We evaluated the association of each dietary phosphorus intake metric with mean SBP and DBP (daytime, nighttime, 24-hour, and clinic), pulse pressure (daytime, nighttime, and 24-hour), and percentage of nocturnal BP dipping using linear regression. Models were adjusted for age, sex, and income level, followed by additional adjustment for diabetes, current smoking status, current alcohol use, eGFR, number of antihypertensive medication classes, total energy intake, and dietary sodium consumption. In models of phosphorus density and energy-adjusted phosphorus, total energy was not included as a covariate because it was already incorporated in these metrics and because exploratory models revealed that results were not meaningfully changed with its inclusion.30,31 Because of the suspected collinearity with energy intake and scaled nutrients, primary models did not include adjustment for body mass index. Sensitivity analyses considered additional adjustment for body mass index.
We used logistic regression with aforementioned adjustments for associations between dietary phosphorus metrics and BP phenotypes. For sustained hypertension, the presence of the phenotype was compared to all other phenotypes (sustained normotension, white-coat hypertension, and masked hypertension) combined and among those with clinic-defined hypertension (sustained vs. white-coat hypertension). Due to the potential impact of kidney disease, diabetes, and antihypertensive medications on BP, we tested for interaction and fit models stratified by eGFR, diabetes, and the number of antihypertensive medication classes being taken. All statistical analyses were performed using RStudio version 0.99.484 (RStudio, Boston, MA) and data as released in the JHS 2016 Vanguard Center Data Package.
RESULTS
Study population and participant characteristics
Of total 5,306 JHS participants, 1,148 performed 24-hour ABPM.16 We excluded 74 participants without a complete 24-hour ABPM recording based on IDACO criteria, 99 participants without reliable dietary intake information,19 and 2 participants with a history of dialysis or kidney transplant. The study population had a mean (±SD) age of 59.3 ± 10.8 years, and 69.3% of participants were female (Table 1).
Table 1.
Characteristics of participants by absolute dietary phosphorus intake (mg/day)
| Characteristic | Overall (N = 973) |
Q1 231–801 (n = 243) |
Q2 802–1,055 (n = 243) |
Q3 1,056–1,420 (n = 243) |
Q4 1,421–3,769 (n = 244) |
|---|---|---|---|---|---|
| Age (years) | 59.3 ± 10.8 | 61.6 ± 10.3 | 59.8 ± 10.8 | 58.7 ± 10.6 | 56.9 ± 10.9 |
| Female | 674 (69.3%) | 198 (81.5%) | 187 (77.0%) | 151 (62.1%) | 138 (56.6%) |
| Income | |||||
| Poor or lower-middle | 326 (33.5%) | 87 (35.8%) | 76 (31.3%) | 88 (36.2%) | 75 (30.7%) |
| Upper-middle or affluent | 532 (54.7%) | 123 (50.6%) | 139 (57.2%) | 131 (53.9%) | 139 (57.0%) |
| Missing data | 115 (11.8%) | 33 (13.6%) | 28 (11.5%) | 24 (9.9%) | 30 (12.3%) |
| Current smoker | 90 (9.2%) | 21 (8.6%) | 15 (6.2%) | 26 (10.7%) | 28 (11.5%) |
| Current alcohol use | 418 (43.0%) | 96 (39.5%) | 98 (40.3%) | 98 (40.3%) | 126 (51.6%) |
| Daytime SBP (mm Hg) | 129.3 ± 13.5 | 129.6 ± 13.5 | 129.4 ± 13.6 | 129.7 ± 12.7 | 128.5 ± 14.1 |
| Daytime DBP (mm Hg) | 77.8 ± 9.2 | 76.9 ± 9.8 | 77.8 ± 8.9 | 77.9 ± 8.6 | 78.8 ± 9.5 |
| Daytime PP (mm Hg) | 51.5 ± 11.2 | 52.7 ± 11.3 | 51.6 ± 11.7 | 51.9 ± 10.9 | 49.8 ± 10.7 |
| Nighttime SBP (mm Hg) | 121.0 ± 15.9 | 120.3 ± 15.7 | 121.5 ± 16.2 | 122.0 ± 16.2 | 120.1 ± 15.8 |
| Nighttime DBP (mm Hg) | 68.3 ± 10.3 | 66.7 ± 9.3 | 68.6 ± 10.3 | 68.7 ± 10.8 | 69.3 ± 10.3 |
| Nighttime PP (mm Hg) | 52.7 ± 11.6 | 53.6 ± 11.8 | 52.9 ± 12.1 | 53.2 ± 11.5 | 50.8 ± 10.8 |
| Hypertension | 614 (63.1%) | 166 (68.3%) | 145 (59.7%) | 161 (66.3%) | 142 (58.2%) |
| Number of anti-HTN classes | 1.12 ± 1.17 | 1.23 ± 1.18 | 1.12 ± 1.17 | 1.14 ± 1.17 | 1.01 ± 1.14 |
| Diabetes | 238 (24.5%) | 64 (26.3%) | 59 (24.3%) | 60 (24.7%) | 55 (22.5%) |
| eGFR (ml/min/1.73 m2) | 91.4 ± 21.2 | 87.1 ± 20.9 | 93.0 ± 18.6 | 93.1 ± 21.2 | 92.3 ± 23.2 |
| <60 | 62 (6.4%) | 22 (9.1%) | 9 (3.7%) | 13 (5.3%) | 18 (7.4%) |
| Albuminuria (mg/g)a | 6.0 (4.0–12.0) | 7.0 (4.0–12.0) | 6.0 (4.0–10.6) | 5.0 (4.0–12.0) | 6.0 (4.0–12.0) |
| Dietary sodium (mg) | 3,247 ± 1,358 | 1,930 ± 512 | 2,726 ± 617 | 3,532 ± 883 | 4,822 ± 1,203 |
| Dietary protein (g) | 75.7 ± 33.8 | 42.7 ± 10.9 | 61.4 ± 12.7 | 81.2 ± 18.1 | 118.1 ± 29.5 |
| Animal protein | 46.9 ± 27.6 | 22.1 ± 7.4 | 34.0 ± 10.3 | 51.1 ± 15.5 | 80.2 ± 27.3 |
| Vegetable protein | 21.2 ± 8.3 | 13.6 ± 3.9 | 19.0 ± 4.7 | 22.7 ± 6.1 | 29.5 ± 8.1 |
| Total energy (kcal) | 1,905 ± 751 | 1,133 ± 314 | 1,624 ± 364 | 2,088 ± 484 | 2,772 ± 572 |
| Dietary folate (μg) | 320.0 ± 135.7 | 223.9 ± 112.6 | 303.1 ± 107.1 | 324.2 ± 101.2 | 428.5 ± 134.1 |
| Dietary calcium (mg) | 843.0 ± 452.7 | 537.8 ± 342.4 | 769.2 ± 396.9 | 871.2 ± 371.8 | 1,192.4 ± 431.8 |
| Dietary magnesium (mg) | 295.1 ± 119.4 | 197.3 ± 82.4 | 260.9 ± 80.6 | 307.2 ± 76.5 | 414.3 ± 113.3 |
| Dietary potassium (mg) | 2,567 ± 1,001 | 1,631 ± 534 | 2,235 ± 565 | 2,723 ± 617 | 3,675 ± 885 |
Mean ± SD shown for continuous variables (unless otherwise indicated), number of participants (proportion) shown for categorical variables. Abbreviations: DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HTN, hypertension; PP, pulse pressure; Q, quartile; SBP, systolic blood pressure.
aMedian (25th percentile to 75th percentile).
Similar to typical dietary intake reported by the United States Department of Agriculture (www.ars.usda.gov), median dietary phosphorus intake in the study population was 1,056 mg/day (interquartile range [IQR]: 802–1,421 mg/day). Scaled to protein intake (phosphorus-to-protein ratio) and total energy intake (phosphorus density), mean (±SD) phosphorus intake was 15.6 ± 3.12 mg/g and 0.614 ± 0.144 mg/kcal, respectively. Median energy-adjusted phosphorus intake was 1,126 mg/day (IQR: 993–1,275 mg/day). Participants with higher absolute phosphorus intake were younger, less likely to be female, and more likely to consume alcohol (Table 1). Absolute dietary phosphorus was highly correlated with intake of total energy (r = 0.83), sodium (r = 0.81), protein (r = 0.89 overall; r = 0.87 for animal protein and r = 0.72 for vegetable protein), and potassium (r = 0.81). Meanwhile, intakes of calcium (r = 0.57), magnesium (r = 0.72), and folate (r = 0.56) were moderately correlated with dietary phosphorus possibly due to nondietary supplements contributing to these nutrients (Supplementary Figures 1 and 2).
Overall, 63.1% of participants had hypertension, 22.5% had diabetes, and 6.4% had an eGFR <60 ml/min/1.73 m2. Mean (±SD) clinic SBP and DBP were 127.1 ± 17.0 and 77.3 ± 10.1 mm Hg, respectively (Table 1). Median nocturnal BP dipping was 6.8% (IQR: 1.6–11.4%), and 66.6% of participants were nondippers (n = 648). Overall, 407 participants (41.8%) had 24-hour hypertension, 250 (25.8%) had clinic hypertension, 98 (10.1%) had sustained hypertension, 306 (31.6%) had masked hypertension, and 152 (15.7%) had white-coat hypertension. The prevalence of these abnormal BP phenotypes was similar across quartiles of dietary phosphorus (Supplementary Table 1).
Dietary phosphorus and blood pressure
There were no statistically significant associations between dietary phosphorus metrics and 24-hour SBP, DBP, or pulse pressure (Table 2). Results were similar in sensitivity analyses with adjustment for body mass index. In contrast to our expectation, higher phosphorus intake metrics were associated with lower daytime and nighttime DBP (Figure 1). Daytime DBP was 1.67 mm Hg lower per 500 mg/day higher absolute phosphorus intake (P = 0.002), 1.45 mm Hg lower per 0.2 mg/kcal higher phosphorus density (P < 0.001), and 1.69 mm Hg lower per 500 mg/day higher energy-adjusted phosphorus intake (P = 0.001). Also, nighttime DBP was 1.32 mm Hg lower per 500 mg/day higher absolute phosphorus intake (P = 0.04), 0.98 mm Hg lower per 0.2 mg/kcal higher phosphorus density (P = 0.04), and 1.26 mm Hg lower per 500 mg/day higher energy-adjusted phosphorus intake (P = 0.04; Figure 2). These associations did not persist when normalizing phosphorus intake to protein. There were no statistically significant relationships between dietary phosphorus and SBP or pulse pressure, daytime or nighttime (Figures 1 and 2).
Table 2.
Association between dietary phosphorus intake and 24-hour blood pressure (mm Hg)
| Unadjusted | Adjusted for demographicsa | Fully adjustedb | ||||
|---|---|---|---|---|---|---|
| Difference | P | Difference | P | Difference | P | |
| 24-hour systolic BP | ||||||
| Per +500 mg/day phosphorus | −0.10 | 0.83 | +0.01 | 0.98 | −0.61 | 0.50 |
| Per +5.0 mg/g phosphorus-to-protein ratio | −0.25 | 0.73 | −0.48 | 0.52 | −0.66 | 0.42 |
| Per +0.2 mg/kcal phosphorus density | −0.22 | 0.72 | −0.37 | 0.55 | −0.49 | 0.49 |
| Per +500 mg/day energy-adjusted phosphorus | −0.32 | 0.69 | −0.51 | 0.53 | −0.55 | 0.52 |
| 24-hour diastolic BP | ||||||
| Per +500 mg/day phosphorus | +0.24 | 0.42 | +0.01 | 0.97 | −0.48 | 0.41 |
| Per +5.0 mg/g phosphorus-to-protein ratio | −1.11 | 0.02 | −0.85 | 0.08 | −0.92 | 0.09 |
| Per +0.2 mg/kcal phosphorus density | −0.43 | 0.28 | −0.30 | 0.47 | −0.30 | 0.51 |
| Per +500 mg/day energy-adjusted phosphorus | −0.50 | 0.34 | −0.40 | 0.45 | −0.41 | 0.46 |
| 24-hour pulse pressure | ||||||
| Per +500 mg/day phosphorus | −0.33 | 0.35 | −0.003 | 0.99 | −0.13 | 0.85 |
| Per +5.0 mg/g phosphorus-to-protein ratio | +0.86 | 0.14 | +0.37 | 0.52 | +0.26 | 0.69 |
| Per +0.2 mg/kcal phosphorus density | +0.21 | 0.67 | −0.08 | 0.88 | −0.19 | 0.73 |
| Per +500 mg/day energy-adjusted phosphorus | +0.18 | 0.78 | −0.11 | 0.86 | −0.14 | 0.84 |
Abbreviation: BP, blood pressure.
aModels were adjusted for age, sex, and income level.
bModels were adjusted for age, sex, income level, diabetes, smoking status, current alcohol use, estimated glomerular filtration rate, number of antihypertensive medication classes, total energy intake, and dietary sodium. In models incorporating energy into the exposure (phosphorus density and energy-adjusted phosphorus intake), total energy was not added as a covariate. In models using phosphorus density as the exposure, we adjusted for sodium density (dietary sodium to total energy).
Figure 1.
Association of dietary phosphorus intake with daytime ambulatory blood pressure (N = 973). Dietary phosphorus was expressed as absolute intake, normalized to protein intake, normalized to total energy intake, and energy-adjusted phosphorus intake, and shown are their relationships with (a) daytime systolic blood pressure, (b) daytime diastolic blood pressure, and (c) daytime pulse pressure. Effect sizes are given in mm Hg, with 95% confidence intervals shown. Models were adjusted for age, sex, income level, diabetes, smoking status, current alcohol use, estimated glomerular filtration rate, number of antihypertensive medication classes, total energy intake, and dietary sodium. In models incorporating energy into the exposure (phosphorus density and energy-adjusted phosphorus intake), total energy intake was not added as a covariate. In models using phosphorus density as the exposure, we adjusted for sodium density (dietary sodium to total energy).
Figure 2.
Association of dietary phosphorus intake with nighttime ambulatory blood pressure. Dietary phosphorus was expressed as absolute intake, normalized to protein intake, normalized to total energy intake, and energy-adjusted phosphorus intake, and shown are their relationships with (a) nighttime systolic blood pressure, (b) nighttime diastolic blood pressure, and (c) nighttime pulse pressure. Effect sizes are given in mm Hg, with 95% confidence intervals shown. Models were adjusted for age, sex, income level, diabetes, smoking status, current alcohol use, estimated glomerular filtration rate, number of antihypertensive medication classes, total energy intake, and dietary sodium. In models incorporating energy into the exposure (phosphorus density and energy-adjusted phosphorus intake), total energy intake was not added as a covariate. In models using phosphorus density as the exposure, we adjusted for sodium density (dietary sodium to total energy).
There were no independent associations of dietary phosphorus metrics with clinic SBP. Higher dietary phosphorus was associated with lower clinic DBP using most metrics in fully adjusted models. Specifically, clinic DBP was 1.43 mm Hg lower per 500 mg/day higher absolute phosphorus intake (P = 0.02), 1.10 mm Hg lower per 5.0 mg/g higher phosphorus-to-protein ratio (P = 0.05), 0.81 mm Hg lower per 0.2 mg/kcal higher phosphorus density (P = 0.09), and 1.14 mm Hg lower per 500 mg/day higher energy-adjusted phosphorus intake (P=0.05). For all SBP, DBP, and pulse pressure measures, there was no evidence of interaction of dietary phosphorus with eGFR, diabetes, or number of antihypertensive medication classes (P interaction > 0.05 for each). Selected results stratified by antihypertensive medication use (none vs. 1 or more classes) are presented in Supplementary Table 2. Results were similar if participants with hypertension at baseline were excluded.
Dietary phosphorus and qualitative BP phenotypes
There were no statistically significant associations between any dietary phosphorus metrics and nocturnal BP dipping or odds of nondipping in adjusted models (Table 3). Higher absolute dietary phosphorus was associated with lower odds of clinic hypertension in univariate and demographic-adjusted analyses (Table 3), but this did not persist after full adjustment. No other associations were present between phosphorus intake and clinic hypertension. There were no associations between phosphorus intake and 24-hour hypertension. Higher dietary phosphorus was associated with reduced odds of sustained hypertension compared to all other phenotypes: odds ratio (OR) 0.56 (95% confidence interval [CI]: 0.33–0.91) per 500 mg/day higher absolute phosphorus intake; OR 0.64 (95% CI: 0.43–0.95) per 5.0 mg/g higher phosphorus-to-protein ratio; OR 0.73 (95% CI: 0.51–1.04) per 0.2 mg/kcal higher phosphorus density; and OR 0.59 (95% CI: 0.37–0.93) per 500 mg/day higher energy-adjusted phosphorus intake (Table 3). Because the reference group includes multiple phenotypes, including lower- and higher-risk groups, we further divided this analysis into subsets defined by high clinic BP (sustained vs. white-coat hypertension) and 24-hour hypertension (sustained vs. masked hypertension). There was a lower odds of sustained hypertension vs. masked hypertension with some dietary phosphorus metrics. However, there were no associations between dietary phosphorus and odds of sustained hypertension vs. white-coat hypertension for any metric (Supplementary Table 3). There were no statistically significant interactions between dietary phosphorus and eGFR, diabetes, or the number of antihypertensive medication classes for any hypertension phenotype.
Table 3.
Association between dietary phosphorus intake and odds of abnormal BP phenotypes
| Unadjusted | Adjusted for demographicsa | Fully adjustedb | |
|---|---|---|---|
| OR (95% CI) | OR (95% CI) | OR (95% CI) | |
| Nondipping nocturnal BP (N = 973; 648 cases) | |||
| Per +500 mg/day phosphorus | 1.11 (0.97−1.28) | 1.15 (1.00−1.33) | 1.05 (0.79−1.39) |
| Per +5.0 mg/g phosphorus-to-protein ratio | 0.96 (0.78−1.20) | 0.91 (0.73−1.14) | 0.92 (0.72−1.19) |
| Per +0.2 mg/kcal phosphorus density | 1.15 (0.95−1.40) | 1.16 (0.95−1.41) | 1.02 (0.82−1.27) |
| Per +500 mg/day energy-adjusted phosphorus | 1.17 (0.92−1.50) | 1.19 (0.93−1.53) | 1.05 (0.80−1.37) |
| Clinic hypertension (N = 969; 250 cases) | |||
| Per +500 mg/day phosphorus | 0.85 (0.73−0.98) | 0.85 (0.72−0.99) | 0.78 (0.56−1.07) |
| Per +5.0 mg/g phosphorus-to-protein ratio | 0.95 (0.75−1.20) | 0.89 (0.69−1.12) | 0.79 (0.60−1.04) |
| Per +0.2 mg/kcal phosphorus density | 0.95 (0.78−1.16) | 0.92 (0.75−1.13) | 0.92 (0.72−1.15) |
| Per +500 mg/day energy-adjusted phosphorus | 0.85 (0.65−1.11) | 0.81 (0.61−1.06) | 0.77 (0.56−1.04) |
| 24-hour hypertension (N = 973; 407 cases) | |||
| Per +500 mg/day phosphorus | 0.98 (0.86−1.11) | 0.99 (0.87−1.13) | 0.85 (0.65−1.10) |
| Per +5.0 mg/g phosphorus-to-protein ratio | 0.98 (0.80−1.21) | 0.97 (0.79−1.20) | 0.96 (0.75−1.21) |
| Per +0.2 mg/kcal phosphorus density | 0.96 (0.80−1.14) | 0.95 (0.79−1.14) | 0.91 (0.75−1.12) |
| Per +500 mg/day energy-adjusted phosphorus | 0.91 (0.72−1.14) | 0.90 (0.71−1.13) | 0.85 (0.66−1.09) |
| Sustained hypertension (N = 969; 98 cases) | |||
| Per +500 mg/day phosphorus | 0.76 (0.59−0.95) | 0.77 (0.60−0.98) | 0.56 (0.33−0.91) |
| Per +5.0 mg/g phosphorus-to-protein ratio | 0.81 (0.57−1.15) | 0.73 (0.51−1.04) | 0.64 (0.43−0.95) |
| Per +0.2 mg/kcal phosphorus density | 0.81 (0.59−1.10) | 0.77 (0.56−1.05) | 0.73 (0.51−1.04) |
| Per +500 mg/day energy-adjusted phosphorus | 0.67 (0.44−1.00) | 0.61 (0.39−0.93) | 0.59 (0.37−0.93) |
Abbreviations: BP, blood pressure; CI, confidence interval; OR, odds ratio.
aModels were adjusted for age, sex, and income level.
bModels were adjusted for age, sex, income level, diabetes, smoking status, current alcohol use, estimated glomerular filtration rate, number of antihypertensive medication classes, total energy intake, and dietary sodium. In models incorporating energy into the exposure (phosphorus density and energy-adjusted phosphorus intake), total energy was not added as a covariate. In models using phosphorus density as the exposure, we adjusted for sodium density (dietary sodium to total energy).
DISCUSSION
We sought to determine the association between dietary phosphorus intake and BP in African Americans. Although prior studies have evaluated the potential role of phosphorus in BP regulation, few studies have investigated this specifically among African Americans or used ABPM which more precisely characterizes 24-hour BP and qualitative BP phenotypes.31–33 This inquiry is highly relevant in light of the high risk of hypertension among African Americans, growing use of phosphorus-based food additives, and myriad reported associations between phosphorus homeostasis, left ventricular hypertrophy, and cardiovascular disease.3–7 Overall, we did not find consistent statistically significant associations between dietary phosphorus intake and BP level or phenotype using any metric of phosphorus intake, including total phosphorus intake, phosphorus-to-protein ratio, phosphorus density, or energy-adjusted phosphorus. By some metrics of phosphorus intake, higher intake was associated with lower daytime and nighttime DBP, but not with 24-hour DBP or pulse pressure. Discrepancies between daytime and nighttime DBP and 24-hour DBP outcomes are likely related to the inclusion of highly variable transition periods in the mornings and evenings in 24-hour measurements.24 However, SBP correlates more strongly with cardiovascular outcomes and thus the relevance of our lower DBP finding is unclear.34,35 Finally, higher phosphorus intake was also associated with reduced odds of sustained hypertension when compared to all other phenotypes, which is a mixture of both higher- and lower-risk phenotypes, such as masked hypertension, white-coat hypertension, and normotension. Evaluating just those with clinic hypertension, a similar association was not observed for sustained hypertension compared to the lower-risk phenotype of white-coat hypertension. For this reason and due to many phenotypes tested, we recommend interpreting this finding cautiously.
We hypothesized that increased dietary phosphorus would be associated with higher BP levels based on the high risk of left ventricular hypertrophy, heart failure, and cardiovascular disease associated with higher serum phosphorus or its regulatory hormones.6,7,36,37 Animal and human studies suggest that phosphorus loading may directly affect vascular compliance, calcification, and vasodilation as a plausible mechanism directly promoting hypertension.13,38–40 Recently, the phosphorus regulatory hormone, fibroblast growth factor 23, was reported to increase the absorption of sodium in the distal tubule of the kidney as another potential mechanism.41 Nonetheless, we did not find associations between high dietary phosphorus intake and BP using clinic or ABPM measures. Prior studies have reported associations between higher dietary phosphorus and lower BP in the United States and internationally.31,32,42 However, all of these studies are limited by the strong correlations between dietary phosphorus and other BP-lowering nutrients, such as calcium, magnesium, potassium, and whole grains.31,32 In fact, the major sources of phosphorus in these prior studies were fish and dairy products, 2 food groups widely thought to improve BP.43 In the Atherosclerosis Risk in Communities Study, the beneficial association between dietary phosphorus intake and BP was only evident for dairy-based phosphorus.32 Nationally representative estimates suggest that grains, including refined grains, are the largest source of dietary phosphorus intake;4 therefore, the relevance of these prior results to current American consumption and across different sources of dietary phosphorus remains unknown. Different dietary sources of phosphorus, such as unprocessed vs. processed meat and dairy, whole vs. refined grains and phosphorus-containing beverages, are each absorbed differently in the gastrointestinal tract, a feature that we were unable to account for fully in this analysis.44,45 In this study, we attempted to isolate the impact of inorganic phosphorus food additives from healthier unprocessed sources by calculating the phosphorus-to-protein ratio, but results were largely unchanged. This method may not be able to fully account for additives as many legumes have high phosphorus-to-protein ratios despite being unprocessed. A more direct method of accounting for phosphorus-based food additives or examining absorbable phosphorus may yield different results.
In addition to the earlier consideration, our study is among the first to evaluate the association between dietary phosphorus and BP in African Americans. Total dietary phosphorus intake is lower in African Americans according to many studies where it may associate with lower levels of dairy and protein intake.4,32 Different patterns of phosphorus sources in African Americans may be responsible for conflicting results between this and prior studies. In fact, in the Atherosclerosis Risk in Communities Study, there was no association between dietary phosphorus intake and incident hypertension among the African American subgroup.32 These disparate findings across groups may suggest that it is dietary patterns and not phosphorus per se that drove the associations with favorable BP.
Our study has some important limitations. First, quantifying dietary phosphorus intake is challenging given incomplete labeling of phosphorus content in many processed foods and reporting biases common to FFQs.46 Additionally, our methodology did not fully account for the differences in animal, plant, and inorganic sources of phosphorus and may not be able to fully adjust for and remove collinearity with other nutrients.47 Another limitation is the relatively small proportion of JHS participants (22%) who underwent ABPM. Although all individuals were invited to participate after completing their baseline visit, there could be unknown confounders associated with ambulatory BP patterns that influenced a participant’s decision to undergo or decline ABPM. Finally, our study was cross-sectional in nature and additional ABPM measurements were not available over follow-up. Our study also had many strengths including the use of a regionally tailored and validated FFQ, gold standard BP measurement methodology, and an adequate sample size.
In summary, higher dietary phosphorus intake was not consistently associated with higher prevalence of hypertension or more adverse BP phenotypes among African Americans. Our findings could imply that the association between disturbed phosphorus homeostasis and cardiovascular disease is mediated by pathways other than BP. However, given the limitations of dietary phosphorus assessment with incomplete accounting of different sources of phosphorus intake, additional studies capturing the complexity of phosphorus content and sources are needed.
Supplementary Material
ACKNOWLEDGMENTS
We thank the staff and participants of the Jackson Heart Study (JHS). The JHS was supported and conducted in collaboration with Jackson State University (HHSN268201300049C and HHSN268201300050C), Tougaloo College (HHSN268201300048C), and the University of Mississippi Medical Center (HHSN268201300046C and HHSN268201300047C) contracts from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Minority Health and Health Disparities (NIMHD). This work was supported by grants T32DK007731 (Dr Olivo), K23DK095949 (Dr Scialla), R0DK1111952 (Dr Scialla), R01DK102134-01 (Dr Boulware), and P30DK096493 (Duke O’Brien Center for Kidney Research) each from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); and HHSN268201300047C (Dr Boulware), HL117323 (Dr Muntner), and F31HL129701 (Dr Booth) from the NHLBI. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHBLI, the National Institutes of Health, or the US Department of Health and Human Services.
DISCLOSURE
The authors declared no conflict of interest.
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