Abstract
Background
The associations of chronic cigarette smoking with blood pressure (BP) remain mixed. It is unclear whether a lack of examination of racial differences contributed to the mixed findings in previous studies. Black smokers metabolize nicotine at a slower rate than White smokers and racial discrimination contributes to nicotine dependence and higher BP among Black smokers.
Methods and Results
We studied the association between cigarette smoking and longitudinal (30‐year) changes in systolic BP, diastolic BP, and pulse pressure (PP) in 4786 Black and White individuals from the CARDIA (Coronary Artery Risk Development in Young Adults) study using repeated‐measures regression models. Neither systolic BP, nor diastolic BP differed between Black consistent smokers compared with Black never smokers, although Black consistent smokers had higher PP than Black never smokers (β=1.01 mm Hg, P=0.028). White consistent smokers had similar systolic BP, but lower diastolic BP (β=−2.27 mm Hg, P<0.001) and higher PP (β=1.59 mm Hg, P<0.001) compared with White never smokers. There were no differences in systolic BP, diastolic BP, or PP between Black or White long‐term former smokers compared with never smokers (all P>0.05).
Conclusions
Although the associations of cigarette smoking with alterations in BP are small, the greater PP observed in consistent smokers may contribute in part to the higher cardiovascular disease risk observed in this group because PP is a strong predictor of cardiovascular disease risk after middle age.
Keywords: cardiovascular disease, hypertension, pulse pressure
Subject Categories: Epidemiology, Cardiovascular Disease, Race and Ethnicity, Risk Factors, Hypertension
Nonstandard Abbreviations and Acronyms
- CARDIA
Coronary Artery Risk Development in Young Adults
Clinical Perspective
What Is New?
The current study demonstrates that both White and Black consistent smokers demonstrate higher pulse pressure compared with never smokers.
We also found that White, but not Black, consistent smokers had lower diastolic blood pressure compared with never smokers.
There were no differences in systolic blood pressure between White or Black consistent smokers and never smokers.
What Are the Clinical Implications?
Findings from the present study highlight the need for practitioners to monitor pulse pressure closely among consistent smokers even before they reach the sixth decade of life when pulse pressure is typically known to increase.
Systolic blood pressure (SBP) increases linearly with age and diastolic blood pressure (DBP) increases until approximately the fifth decade of life and then typically declines, causing a widening of pulse pressure (PP). 1 The development of hypertension (SBP ≥130 and/or DBP ≥80) is strongly associated with an increased risk of developing cardiovascular disease (CVD). 2 In addition to the association between advancing age and increased BP, several modifiable CVD risk factors are also associated with increased BP including obesity, physical inactivity, and an unhealthy diet. 3 Chronic cigarette smoking is a known CVD risk factor, and past reports from the World Health Organization have suggested that cigarette smoking is responsible for ≈10% of all CVD deaths worldwide. 4 However, despite the known association between cigarette smoking and increased CVD risk, the relation between cigarette smoking and BP remains unclear.
Acutely, cigarette smoking invokes a sympathetically mediated pressor response that causes a rise in BP that lasts for ≈15 minutes. 5 However, the chronic effects of cigarette smoking on BP remain mixed. Several cross‐sectional, epidemiological studies have demonstrated a paradoxical relation between cigarette smoking and BP in that current smokers have similar or lower SBP and DBP compared with nonsmokers even after adjusting for BMI. 5 , 6 , 7 , 8 In contrast, other studies have demonstrated that SBP was higher among current smokers compared with nonsmokers. 9 , 10
The discrepancies in these findings may be in part from a lack of examination of racial differences, because the influence of race on the association between cigarette smoking and BP remains unclear. Black smokers metabolize nicotine at a slower rate than White smokers. 11 , 12 , 13 , 14 Importantly, a higher presence of serum cotinine, a metabolite of nicotine, is associated with increased activation of the renin‐angiotensin‐aldosterone system, a pathway commonly associated with hypertension. 11 , 15 Consistent with this, studies have also demonstrated that nicotine invokes acute increases in BP. 16 , 17 Therefore, it is possible that chronic renin‐angiotensin‐aldosterone activation, in part from slower nicotine metabolism, may be associated with higher BP in Black current smokers compared with Black nonsmokers; however, little is known about this relation to date. In addition to potential differences in nicotine metabolism among Black and White smokers, the effects of racial discrimination may also contribute to higher BP among Black smokers. Previous CARDIA (Coronary Artery Risk in Development in Young Adults) studies and others have demonstrated that racial discrimination is associated with higher BP among Black adults. 18 , 19 , 20 , 21 , 22 , 23 Furthermore, everyday discrimination is associated with nicotine dependence among Black people. 24 , 25 There is a lack of information on the extent to which genetic differences in nicotine metabolism versus psychosocial influences such as discrimination and racism influence BP among cigarette smokers. However, it is possible that both genetic differences in nicotine metabolism as well as the effects of discrimination towards Black people may result in higher BP among Black smokers compared with White smokers. 24 Because of the potential racial differences in the effects of cigarette smoking on BP and the conflicting findings from previous cross‐sectional studies, additional research using longitudinal study designs that account for several time‐varying confounders are needed to examine the associations of cigarette smoking on changes in BP over time in both Black and White individuals.
In the present study, using data from the CARDIA cohort, we aimed to examine racial differences in longitudinal changes in BP over 30 years (1985–2016) in never smokers and consistent smokers. Based on previous findings, we hypothesized that Black consistent smokers will have higher BP and White consistent smokers will have lower or similar BP over 30 years compared with never smokers of the same race and sex. We also hypothesized that Black and White long‐term former smokers would have similar or higher BP compared with Black and White never smokers from the same time frame.
Methods
Requests to access the data set, analytic methods, and study materials may be sent to the CARDIA Study Coordinating Center. Contact information can be found on the CARDIA website. 26
Study Participants
CARDIA is a multicenter, longitudinal study of the influence of behavioral, demographic, and physiological factors on the presence and development of CVD risk factors in young adults in the United States. The initial study cohort consisted of 5115 young adult participants, balanced on age, sex, race (Black and White people), and educational status, who had an in‐person clinical examination in 1985 to 1986 (baseline) from 1 of 4 field centers: Birmingham, AL; Minneapolis, MN, Chicago, IL, or Oakland, CA. Subsequent in‐person examinations were held every 2 to 5 years including year 2 (1987–1988), year 5 (1990–1991), year 7 (1992–1993), year 10 (1995–1996), year 15 (2000–2001), year 20 (2005–2006), year 25 (2010–2011), and year 30 (2015–2016). Retention of the surviving cohort at examination years 2, 5, 7, 10, 15, 20, 25, and 30 was 91%, 85%, 80%, 77%, 74%, 72%, 72%, and 71%, respectively. 27 Details of the CARDIA eligibility criteria have been published previously. 28 The institutional review board at each center approved all study protocols for the primary CARDIA examination, as well as all ancillary studies. Written informed consent was obtained at each examination.
Exclusions and Inclusions
In this young, healthy cohort at baseline, no participants were excluded from the current analyses on the basis of medical conditions. A total of 236 individuals who did not have 2 BP measurements taken at least 5 years apart were excluded, for an analytic sample of 4786 individuals.
Assessment of Smoking Status
Smoking status was assessed at each of the examinations using the CARDIA Tobacco Use questionnaire, and 4 cigarette‐smoking groups were formed using previously defined criteria. 29 Never smokers were considered the reference group and included those who reported not having smoked at any of the examinations where data on smoking status were available, including former smokers at baseline (ie, if an individual never reported current smoking status or former smoking status after baseline). Long‐term former smokers were defined as individuals who reported smoking at year 0 or 2 but not at all subsequent examinations (ie, if an individual never reported current smoking after year 2). Consistent smokers were defined as individuals who reported smoking cigarettes at all available examinations (ie, all assessed examinations with current smoking status). The fourth smoking group included individuals with all other patterns of smoking (ie, individuals who reported smoking at 1 or more time points but did not meet the requirements to be classified as a consistent or long‐term former smoker).
To better categorize individuals into smoking groups, missing assessments on smoking status were imputed before individuals were grouped into the smoking categories described above. For individuals with the same smoking status before and after missing assessments, the missing smoking status was imputed using the nearest available smoking status. The missing assessments were only imputed for individuals with up to 3 consecutive missing values and up to a total of 4 missing values (50% of all examinations). If they had >4 missing assessments, smoking status was categorized as missing. There were 44 individuals with missing smoking status at year 0. For these individuals, the subsequent assessments on smoking status were manually inspected and categorized into 1 of 4 groups using the criteria described above. Previous studies in this cohort have demonstrated a strong relation between self‐reported cigarette smoking and Year 0 serum cotinine measurements. 29
Assessment of BP
BP measurements were collected on each participant following 5 minutes of quiet rest for all examination years. Three BP measurements were taken from the right arm while participants rested in an upright, seated position. The second and third BP readings were averaged for analyses. For the baseline to year 15 examinations, BP was measured using the Hawksley random zero sphygmomanometer. Because of the risks of mercury toxicity, Hawksley no longer manufactures or services this device. As a result, beginning in year 20 the Omron HEM907CL device was used for all BP measurements, calibrated to the random zero value. The primary BP outcomes include SBP and DBP. PP was also calculated by subtracting SBP‐DBP. Treatment effects of antihypertensive medication were accounted for by adding 10 mm Hg to the observed SBP and 5 mm Hg to the observed DBP in treated participants. This technique has been previously described and has been demonstrated to be a more accurate approach to accounting for antihypertensive therapy than by including antihypertensive medication use as a covariate. 30 , 31
Covariates
Baseline covariates included study center, sex, and race (Black people/White people). Time‐varying covariates included age, education, alcohol consumption, physical activity, BMI, plasma lipids, pack‐year smoking history, hypertension medication use (yes/no), history of CVD (yes/no), and history of diabetes mellitus (yes/no). Age was assessed at baseline by self‐reported birth date and was then calculated for each subsequent examination year. Education status was based on the self‐reported number of years of school completed. Alcohol consumption was determined by self‐reported number of alcoholic beverages to calculate the average milliliters of alcohol consumed per day. Physical activity was determined using the CARDIA physical activity history questionnaire that assesses self‐reported frequency of participation in 13 categories of sports and exercise over the previous 12 months. 32 BMI was calculated using measured height and weight (kg/m2). Plasma lipids were measured from a blood sample in the morning following an overnight fast. Pack‐year smoking history was determined as the cumulative cigarette pack‐years (cigarette packs smoked per day multiplied by the number of years smoking) for baseline through year 30. History of CVD, antihypertensive medication use, and diabetes mellitus were determined by self‐report.
Statistical Analysis
One‐way ANOVA tests were used to compare participant characteristics across smoking status groups. Mixed‐effects linear regression models were used to examine the association between cigarette smoking and longitudinal changes in SBP, DBP, and PP from baseline to year 30 never smokers, long‐term former smokers, consistent smokers, and individuals with all other smoking patterns (separate models for each outcome) while stratifying by race. Because previous studies have demonstrated sex differences in the association between cigarette smoking and BP, 9 , 33 in exploratory analyses we also stratified by sex. The exposure, smoking status, was modeled as a categorical variable (4 groups) and each outcome (SBP, DBP, and PP) was modeled as a continuous variable. Model 1 was adjusted for study center and sex as well as time‐varying age. Model 2 additionally adjusted for time‐varying BMI, self‐reported history of CVD, physical activity, education, and pack‐year smoking history. Model 3 additionally adjusted for time‐varying alcohol consumption, plasma lipid concentrations, and diabetes mellitus. All models are described algebraically in Table S1. In sensitivity analyses, we adjusted for antihypertensive medication use, rather than adding 10 mm Hg to SBP and 5 mm Hg to DBP. 30 , 31 As an alternate approach, we also stratified participants by antihypertensive medication use. All mixed‐effects linear regression models used a compound symmetry covariance structure. Data were analyzed with SAS software version 9.4 and statistical significance was set at P<0.05.
Results
Baseline participant characteristics by smoking status group are presented in Table 1. There were statistically significant differences across groups for sex, race, education, alcohol consumption, high‐density lipoprotein, triglycerides, DBP, and PP. As expected, groups also differed by pack‐year smoking history. Mean values for SBP, DBP, and PP across examination years by smoking status and race, without adjusting for any covariates, are included in Table S2.
Table 1.
Baseline Participant Characteristics (1985–1986), the CARDIA Study
| Never Smokers (n=2583) | Long‐Term Former Smokers (n=190) | Consistent Smokers (n=601) | Other Smoking Patterns (n=1412) | P Value | |
|---|---|---|---|---|---|
| Age, y | 24.9±3.7 | 25.3±3.3 | 24.9±3.7 | 24.8±3.6 | 0.469 |
| Sex (n,% female) | 1455 (56) | 111 (58) | 292 (49) | 769 (54) | 0.005 * |
| Race (n, % Black) | 1227 (48) | 86 (45) | 391 (65) | 720 (51) | <0.001 * |
| BMI, kg/m2 | 24.4±5.0 | 24.5±4.9 | 24.4±5.4 | 24.7±5.0 | 0.395 |
| Baseline smoking history (pack‐y) median, IQR | 0±0 | 1.2±4.2 | 5.0±8.0 | 1.2±5.0 | <0.001 * |
| Years of education | 14.4±2.2 | 13.7±2.2 | 12.3±1.7 | 13.4±2.1 | <0.001 * |
| Alcohol consumption (mL/d) median, IQR | 2.4±9.7 | 7.5±24.2 | 9.9±28.6 | 7.5±19.3 | <0.001 * |
| Total MVPA (exercise units) median, IQR | 366.5±393.0 | 352.5±313.0 | 331.0±353.0 | 365.0±378.5 | 0.099 |
| Cardiovascular variables | |||||
| SBP, mm Hg | 111±11 | 110±11 | 111±12 | 110±11 | 0.096 |
| DBP, mm Hg | 69±9 | 67±10 | 68±11 | 68±10 | <0.001 * |
| PP, mm Hg | 42±9 | 43±10 | 43±9 | 42±10 | <0.001 * |
| HR, bpm | 69±11 | 70±10 | 70±11 | 69±11 | 0.172 |
| High BP (n, % yes) | 216 (8) | 21 (11) | 60 (10) | 138 (10) | 0.296 |
| Antihypertension medication use (n, % yes) | 53 (2) | 4 (2) | 20 (3) | 31 (2) | 0.534 |
| Heart problem (n, % yes) | 150 (6) | 17 (9) | 30 (5) | 84 (6) | 0.537 |
| Total cholesterol, mg/dL | 177.3±32.5 | 179.5±36.9 | 176.1±36.1 | 176.9±34.0 | 0.662 |
| HDL‐cholesterol, mg/dL | 53.5±12.5 | 54.2±15.3 | 51.9±14.5 | 52.9±13.2 | 0.030 * |
| LDL‐cholesterol, mg/dL | 110.1±30.3 | 109.6±35.2 | 107.9±34.2 | 108.8±31.4 | 0.378 |
| Triglycerides (mg/dL) median, IQR | 59.0±36.0 | 64.0±42.0 | 67.0±41.0 | 64.0±41.0 | <0.001 * |
| Diabetes mellitus (n, % yes) | 17 (0.6) | 1 (0.5) | 7 (1) | 14 (1) | 0.474 * |
All data are mean±SD unless otherwise specified. Note: All blood pressure measurements are adjusted for antihypertension medication use by adding 10 mm Hg to SBP and 5 mm Hg to DBP in individuals who reported taking antihypertension medication. The “other smoking patterns” category includes individuals who reported smoking at 1 or more time points but did not meet the requirements to be classified as a current or former smoker. BMI indicates body mass index; CARDIA, Coronary Artery Risk Development in Young Adults; DBP, diastolic blood pressure; HDL, high‐density lipoprotein; HR, heart rate; IQR, interquartile range; LDL, low‐density lipoprotein; MVPA, moderate‐vigorous physical activity; PP, pulse pressure; and SBP, systolic blood pressure.
P<0.05.
Thirty‐Year Longitudinal Association Between Cigarette Smoking and BP by Race
As seen in Table 2, SBP did not differ between Black or White consistent smokers compared with Black or White never smokers (Model 3). White consistent smokers had lower DBP (Model 3; β=−2.27, P<0.001) compared with White never smokers; however, DBP did not differ between Black consistent smokers compared with Black never smokers. PP was greater among both Black and White consistent smokers compared with Black and White never smokers (Black: Model 3; β=1.01, P=0.028; White: Model 3; β=1.59, P<0.001). There were no differences in SBP, DBP, or PP between either Black or White long‐term former smokers compared with never smokers. White smokers with other smoking patterns had lower SBP (Model 3; β=−1.42, P<0.001) and DBP (Model 3; β=−1.50, P<0.001), but no difference in PP compared with White never smokers. In contrast, there were no differences in SBP, DBP, or PP between Black smokers with other smoking patterns compared with Black never smokers.
Table 2.
Thirty‐Year Longitudinal Association Between Cigarette Smoking and BP Stratified by Race, Adding 10 mm Hg to SBP and 5 mm Hg to DBP for Individuals on Antihypertensive Medication (1985–2016)
| Consistent Smoker vs Never Smoker | Long‐Term Former Smoker vs Never Smoker | Other Smoking Patterns vs Never Smoker | ||||
|---|---|---|---|---|---|---|
| β (SE) | P Value | β (SE) | P Value | β (SE) | P Value | |
| Black | ||||||
| Model 1 | ||||||
| SBP | 1.70 (0.59) | 0.004* | 0.32 (1.11) | 0.777 | 0.42 (0.47) | 0.369 |
| DBP | 0.00 (0.45) | 0.996 | −1.00 (0.84) | 0.234 | −0.37 (0.35) | 0.290 |
| PP | 1.59 (0.40) | <0.001* | 1.52 (0.74) | 0.042* | 0.87 (0.32) | 0.006* |
| Model 2 | ||||||
| SBP | 1.15 (0.65) | 0.076 | −0.30 (1.08) | 0.781 | −0.08 (0.48) | 0.860 |
| DBP | −0.26 (0.49) | 0.603 | −1.37 (0.82) | 0.093 | −0.61 (0.36) | 0.090 |
| PP | 1.20 (0.45) | 0.008* | 1.17 (0.74) | 0.114 | 0.55 (0.33) | 0.098 |
| Model 3 | ||||||
| SBP | 0.58 (0.66) | 0.381 | −0.44 (1.09) | 0.687 | −0.30 (0.48) | 0.537 |
| DBP | −0.69 (0.50) | 0.167 | −1.25 (0.82) | 0.125 | −0.69 (0.36) | 0.060 |
| PP | 1.01 (0.46) | 0.028* | 0.92 (0.75) | 0.217 | 0.39 (0.33) | 0.250 |
| White | ||||||
| Model 1 | ||||||
| SBP | 1.79 (0.65) | 0.006* | 0.24 (0.88) | 0.780 | 0.11 (0.40) | 0.778 |
| DBP | 0.12 (0.52) | 0.824 | 0.00 (0.70) | 0.994 | −0.14 (0.32) | 0.674 |
| PP | 1.71 (0.40) | <0.001* | 0.42 (0.54) | 0.429 | 0.23 (0.25) | 0.362 |
| Model 2 | ||||||
| SBP | 0.34 (0.70) | 0.624 | −0.19 (0.83) | 0.822 | −0.86 (0.40) | 0.033* |
| DBP | −1.36 (0.56) | 0.016* | −0.40 (0.67) | 0.551 | −1.07 (0.33) | 0.001* |
| PP | 1.62 (0.47) | <0.001* | 0.31 (0.54) | 0.560 | 0.12 (0.27) | 0.645 |
| Model 3 | ||||||
| SBP | −0.66 (0.69) | 0.343 | −0.82 (0.82) | 0.314 | −1.42 (0.40) | <0.001* |
| DBP | −2.27 (0.55) | <0.001* | −0.97 (0.65) | 0.133 | −1.50 (0.32) | <0.001* |
| PP | 1.59 (0.47) | <0.001* | 0.27 (0.54) | 0.620 | 0.05 (0.27) | 0.863 |
The “other smoking patterns” category includes individuals who reported smoking at 1 or more time points but did not meet the requirements to be classified as a current or former smoker. Model 1 adjusts for center, age, and sex. Model 2 additionally adjusts for BMI, history of CVD, MVPA, education, and pack‐years. Model 3 additionally adjusts for alcohol, HDL‐C, LDL‐C, total cholesterol, triglycerides, and diabetes mellitus. BMI indicates body mass index; CVD, cardiovascular disease; DBP, diastolic blood pressure; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; MVPA, moderate‐vigorous physical activity; PP, pulse pressure; and SBP, systolic blood pressure.
P<0.05.
Findings for both Black and White smokers were similar in magnitude and statistical significance in sensitivity analyses that include the unadjusted BP measurements and added antihypertension medication use as a time‐varying covariate (Table S3). Findings stratified by antihypertension medication use are presented in Table S4. Among individuals who reported using antihypertensive medication at any examination year, there were no differences in SBP, DBP, or PP between Black and White consistent smokers, long‐term former smokers, and individuals with other smoking patterns compared with never smokers. In contrast, Black and White consistent smokers who did not report using antihypertensive medication had lower DBP and higher PP compared with never smokers.
Thirty‐Year Longitudinal Association Between Cigarette Smoking and BP Stratified by Race and Sex
Exploratory analyses were conducted to examine sex differences in the relation between cigarette smoking and BP. Fully adjusted models only are presented in Table 3. There were no differences in SBP between Black or White male and female consistent smokers compared with never smokers of the same race and sex. White male and female consistent smokers had lower DBP compared with White male and female never smokers (White men: β=−2.23, P=0.003; White women: β=−2.44, P=0.002). However, DBP did not differ between Black male or female consistent smokers compared with Black male and female never smokers. Black and White female consistent smokers demonstrated greater PP compared with never smokers of the same race and sex (Black women: β=1.38, P=0.030; White women: β=1.96, P=0.002). Additionally, White male long‐term former smokers had lower DBP compared with White male never smokers (β=−2.61, P=0.010). White women, White men, and Black men with other smoking patterns demonstrated lower DBP compared with never smokers of the same race and sex (White women: β=−1.95, P<0.001; White men: β=−1.15, P=0.013; Black men: β=−1.26, P=0.020). White women with other smoking patterns also demonstrated lower SBP compared with White female never smokers (β=−1.67, P=0.002).
Table 3.
Thirty‐Year Longitudinal Association Between Cigarette Smoking and BP Stratified by Race and Sex Group, Adding 10 mm Hg to SBP and 5 mm Hg to DBP for Individuals on Antihypertensive Medication (1985–2016)
| Consistent Smoker vs Never Smoker | Long‐Term Former Smoker vs Never Smoker | Other Smoking Patterns vs Never Smoker | ||||
|---|---|---|---|---|---|---|
| β (SE) | P Value | β (SE) | P Value | β (SE) | P Value | |
| Black men | ||||||
| SBP | −0.13 (0.90) | 0.879 | 0.97 (1.50) | 0.517 | −0.56 (0.68) | 0.405 |
| DBP | −1.19 (0.73) | 0.100 | −0.57 (1.20) | 0.636 | −1.26 (0.54) | 0.020* |
| PP | 0.57 (0.68) | 0.399 | 1.71 (1.10) | 0.122 | 0.54 (0.50) | 0.278 |
| White men | ||||||
| SBP | −1.11 (0.97) | 0.254 | −2.18 (1.31) | 0.098 | −1.29 (0.60) | 0.031* |
| DBP | −2.23 (0.76) | 0.003* | −2.61 (1.01) | 0.010* | −1.15 (0.46) | 0.013* |
| PP | 1.17 (0.70) | 0.093 | 0.64 (0.91) | 0.479 | −0.12 (0.42) | 0.777 |
| Black women | ||||||
| SBP | 0.80 (0.95) | 0.400 | −1.88 (1.54) | 0.222 | −0.37 (0.68) | 0.592 |
| DBP | −0.68 (0.69) | 0.327 | −1.96 (1.11) | 0.079 | −0.38 (0.49) | 0.444 |
| PP | 1.38 (0.63) | 0.030* | 0.13 (1.01) | 0.897 | 0.12 (0.45) | 0.795 |
| White women | ||||||
| SBP | −0.38 (0.99) | 0.699 | −0.21 (1.05) | 0.843 | −1.67 (0.54) | 0.002* |
| DBP | −2.44 (0.80) | 0.002* | −0.23 (0.84) | 0.785 | −1.95 (0.43) | <0.001* |
| PP | 1.96 (0.64) | 0.002* | 0.09 (0.65) | 0.892 | 0.18 (0.34) | 0.601 |
The “other smoking patterns” category includes individuals who reported smoking at 1 or more time points but did not meet the requirements to be classified as a consistent or long‐term former smoker. Model adjusts for center, age, BMI, history of CVD, MVPA, education, pack‐years, alcohol, HDL‐C, LDL‐C, total cholesterol, triglycerides, and diabetes mellitus. BMI indicates body mass index; CVD, cardiovascular disease; DBP, diastolic blood pressure; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; MVPA, moderate‐vigorous physical activity; PP, pulse pressure; and SBP, systolic blood pressure.
P<0.05.
Findings for both Black and White smokers were similar in magnitude and statistical significance in sensitivity analyses that include the unadjusted BP measurements and added antihypertension medication use as a time‐varying covariate (Table S5). Findings stratified by antihypertension medication use are presented in Table S6. Among individuals who reported using antihypertensive medication at any examination year, White female consistent smokers had greater PP compared with White female never smokers. Among individuals who did not report using antihypertensive medication, Black male and White male and female consistent smokers had lower DBP compared with never smokers, and White male and female consistent smokers also had higher PP.
Discussion
The major and novel finding of the present study was that consistent smokers demonstrated greater PP compared with never smokers and the increased PP was most pronounced in Black and White women. Consistent smokers demonstrated slightly lower DBP (≈0.5–2 mm Hg lower) compared with never smokers, although not all associations were statistically significant. The lower DBP may have contributed to the higher PP in consistent smokers compared with never smokers because there were no differences in SBP between these groups. Long‐term former smokers and individuals with all other smoking patterns demonstrated lower DBP, and individuals with other smoking patterns also demonstrated lower SBP compared with never smokers. There were no differences in PP between long‐term former smokers and individuals with all other smoking patterns compared with never smokers.
Although acute cigarette smoking is known to cause a brief rise in BP, the chronic effects of cigarette smoking on BP remain mixed. Several studies have demonstrated that current smokers have similar or lower DBP compared with nonsmokers. In contrast, other studies have demonstrated greater DBP among current smokers compared with nonsmokers. 9 , 10 Consistent with this, the findings pertaining to SBP among current smokers also remain conflicting. Li et al demonstrated no difference in SBP among current smokers compared with never smokers. 7 In contrast, Imamura et al demonstrated lower SBP among moderate‐heavy male smokers, whereas other studies have demonstrated greater SBP among older moderate‐heavy male smokers. 8 , 9 Although it has been suggested that a lower BMI among current smokers may contribute to the lower BP observed in some studies, several studies have demonstrated lower BP among current smokers even after adjusting for BMI. Therefore, it is likely that several additional factors may be responsible for the discrepancies in these findings, including the lack of examination of racial differences and/or the lack of adjustment for potential confounding factors including smoking pack‐years, alcohol consumption, lipid concentrations, physical activity levels, antihypertension medication use, and the presence of comorbidities. After examining racial differences and adjusting for numerous covariates known to influence BP, the findings for DBP in the present study are in line with several previous analyses demonstrating that current smokers tend to have lower DBP compared with never smokers. 7 , 8 , 9 However, we found that the lowest DBP was observed among White male and female consistent smokers compared with never smokers. These findings suggest that the magnitude of the association between cigarette smoking and lower DBP may be stronger in White consistent smokers than Black consistent smokers. Our findings for SBP are in line with those of Li et al and suggest that there are no differences in SBP between consistent smokers and never smokers.
Based solely on the findings that DBP tends to be slightly lower in consistent smokers and that cigarette smoking was not associated with higher SBP, it may be assumed that the association between cigarette smoking and CVD risk is not mediated through increased BP. However, one of the most novel findings of the current study was that PP tended to be higher among consistent smokers compared with never smokers, particularly among women. Importantly, Franklin and colleagues (1999) reported that individuals who demonstrate small increases in PP over time, but who have no changes in SBP over the same timeframe, are at greater CVD risk than individuals who demonstrate increases in SBP over time in the absence of changes in PP over the same timeframe. 1 Therefore, the greater PP demonstrated among consistent smokers in the present study, even in the absence of greater SBP, may contribute in part to the increased CVD risk observed among consistent cigarette smokers. In the present study, the increased PP demonstrated in consistent smokers compared with never smokers was small (≈1–2 mm Hg higher); however, because Franklin and colleagues (1999) demonstrated that small increases in PP were associated with greater CVD risk, these findings may have important clinical significance. Furthermore, individuals in the present study were relatively young (baseline median age: 25 years old; 30‐year follow‐up median age: 51 years old) and the magnitude of the difference in PP between consistent smokers and never smokers could continue to progress over time. Following the sixth decade of life, SBP continues to rise with advancing age; however, DBP decreases, leading to increased PP. 1 Therefore, if consistent smokers are already demonstrating higher PP over their young and early middle‐aged years, it is possible that the increase in PP commonly seen after the sixth decade and continuing into older age may be steeper in consistent smokers than in never smokers, especially among female consistent smokers.
It is likely that the consistent trends towards slightly lower DBP observed in consistent smokers may have contributed to the greater PP demonstrated in this group. The mechanisms underlying the slightly lower DBP demonstrated among consistent smokers in the present study remain unknown; however, it is likely that lower total vascular resistance may contribute. Indeed, current smokers demonstrate lower total vascular resistance compared with never smokers and this is thought to be mediated in part by the vasodilatory effects of cotinine, a metabolite of nicotine, and carbon monoxide. 34 Interestingly, DBP tended to be lower among White consistent smokers compared with Black consistent smokers. Therefore, it is possible that the effects of cotinine and carbon monoxide on total vascular resistance are more pronounced among White consistent smokers or that the effects of racial discrimination blunt the vasodilatory effects of cotinine and carbon monoxide among Black consistent smokers. Future studies that measure cotinine and carbon monoxide concentrations, racial discrimination, total vascular resistance, and BP in the same individuals are needed to better understand these mechanisms.
In addition to the potential effects of cotinine and carbon monoxide, there are likely additional mechanisms contributing to the lower DBP, and ultimately higher PP among consistent smokers, especially among women. Lawless et al demonstrated that the association between perceived stress and nicotine dependence is stronger among women compared with men. 35 However, it is important to note that the majority of women included in the study by Lawless and colleagues were non‐Hispanic, White women. 35 This is important because in the present study, the White female consistent smokers demonstrated the lowest DBP compared with never smokers. While future studies examining racial differences in the association between perceived stress and nicotine dependence are needed, it is possible that stress relief from smoking has a more pronounced effect on BP among White female consistent smokers compared with Black female consistent smokers. Although greater PP was most pronounced among both White and Black female consistent smokers, it is possible that different mechanisms may contribute to the greater PP among each group separately. For example, while Black female consistent smokers demonstrated slightly lower DBP, they were the only group that trended to have higher SBP, suggesting that both lower DBP and higher SBP contributed to the greater PP observed in this group. The mechanisms contributing to the lower DBP and higher SBP among Black female consistent smokers cannot be determined in the present study; however, it is possible that greater large elastic central artery stiffness may have contributed. Stiffening of the large elastic central arteries (eg, aorta) decreases the ability of these vessels to distend in response to increased BP during systole and recoil during diastole. 36 This in turn results in increases in SBP, reductions in DBP, and a widening of PP. While the effects of cigarette smoking on large elastic central artery stiffness remain controversial, 37 , 38 , 39 it is possible that cigarette smoking increases large elastic central artery stiffness, and therefore PP, among Black women and that this may be attributed to several potential mechanisms such as greater increases in sympathetic nerve activity following smoking or the effects of discrimination. A recent study by Bromfield et al demonstrated that discrimination is associated with greater aortic stiffness among Black women, but not among Black or White men or White women. 40 While the study by Bromfield and colleagues adjusted for a history of cigarette smoking in their analysis, additional studies in current and never smokers are needed to further explore the interplay between discrimination, nicotine dependence, increased large elastic central artery stiffness, and greater PP among Black women.
In the present study, the increased PP was only observed in the consistent smokers and not long‐term former smokers, suggesting that there may be no association between cigarette smoking and increased PP if an individual ceased smoking. Among long‐term former smokers, the mechanisms underlying the lower DBP demonstrated among White male long‐term former smokers as well as the nonsignificant trends in lower SBP remain unknown. It is important to note that in the present study, long‐term former smokers smoked at the first and/or second examinations and then did not report smoking at any of the following examinations. Therefore, long‐term former smokers in the present study quit smoking in their early adulthood years and had refrained from smoking for at least 25 years of follow‐up period. It is possible that after quitting smoking, the long‐term former smokers in the present study also engaged in other positive lifestyle factors that are associated with lower BP. Although numerous factors that are known to influence BP were included as covariates in the present study, additional lifestyle‐based covariates, including nutritional factors such as dietary sodium intake, are needed to further examine the relation between long‐term smoking cessation and BP.
The results of the present study should be interpreted in the context of several limitations. First, because of the large variety of other smoking patterns included in the “other smoking patterns” category, mechanisms as to why individuals with other smoking patterns have lower DBP, and for White women, higher SBP, are not able to be determined. Future studies examining the association between other smoking patterns and BP, including patterns that have periods of abstinence and then relapse, are needed. Second, former smokers in this study had refrained from smoking for ≈25 years. Future studies should examine differences in BP between Black and White smokers following shorter durations of smoking cessation.
Conclusions
In conclusion, the novel finding from the present study was that consistent smokers demonstrated higher PP compared with never smokers and the increased PP was most pronounced in female consistent smokers. The slightly higher PP observed in consistent smokers may contribute in part to the greater CVD risk observed in this group. Future studies are needed to determine whether the increase in PP with aging is greater among consistent smokers compared with never smokers and whether higher PP is associated with greater CVD risk in consistent smokers. Future studies are also needed to determine whether lower total vascular resistance contributes to the higher PP demonstrated in current smokers. Finally, consistent with previous studies on former smokers, cigarette smoking does not appear to differ between long‐term former smokers and never smokers, suggesting that there is no association between long‐term smoking and greater BP in this group. 41 , 42
Sources of Funding
The CARDIA (Coronary Artery Risk Development in Young Adults) Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). Additional funding was provided by NHLBI R01 HL122477 (CARDIA Lung Study). This article has been reviewed by CARDIA for scientific content. Luehrs was supported by American Heart Association (19PRE34400003) and Pierce by a University of Iowa Environmental Health Sciences Research Center pilot grant from NIEHS (P30 ES005605).
Disclosures
None.
Supporting information
Tables S1–S6
(J Am Heart Assoc. 2021;10:e019566. DOI: 10.1161/JAHA.120.019566.)
Supplementary Material for this article is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.120.019566
This manuscript was sent to Eric E. Smith, MD, MPH, Guest Editor, for review by expert referees, editorial decision, and final disposition.
For Sources of Funding and Disclosures, see page 9.
References
- 1. Franklin SS, Khan SA, Wong ND, Larson MG, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease? The Framingham Heart Study. Circulation. 1999;100:354–360. DOI: 10.1161/01.CIR.100.4.354. [DOI] [PubMed] [Google Scholar]
- 2. Group SR , Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, et al. A randomized trial of intensive versus standard blood‐pressure control. N Engl J Med. 2015;373:2103–2116. DOI: 10.1056/NEJMoa1511939. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Kokubo Y. Prevention of hypertension and cardiovascular diseases: a comparison of lifestyle factors in Westerners and East Asians. Hypertension. 2014;63:655–660. DOI: 10.1161/HYPERTENSIONAHA.113.00543. [DOI] [PubMed] [Google Scholar]
- 4. Messner B, Bernhard D. Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler Thromb Vasc Biol. 2014;34:509–515. DOI: 10.1161/ATVBAHA.113.300156. [DOI] [PubMed] [Google Scholar]
- 5. Rhee MY, Na SH, Kim YK, Lee MM, Kim HY. Acute effects of cigarette smoking on arterial stiffness and blood pressure in male smokers with hypertension. Am J Hypertens. 2007;20:637–641. DOI: 10.1016/j.amjhyper.2006.12.017. [DOI] [PubMed] [Google Scholar]
- 6. Green MS, Jucha E, Luz Y. Blood pressure in smokers and nonsmokers: epidemiologic findings. Am Heart J. 1986;111:932–940. DOI: 10.1016/0002-8703(86)90645-9. [DOI] [PubMed] [Google Scholar]
- 7. Li G, Wang H, Wang KE, Wang W, Dong F, Qian Y, Gong H, Hui C, Xu G, Li Y, et al. The association between smoking and blood pressure in men: a cross‐sectional study. BMC Public Health. 2017;17:797. DOI: 10.1186/s12889-017-4802-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Imamura H, Tanaka K, Hirae C, Futagami T, Yoshimura Y, Uchida K, Tanaka A, Kobata D. Relationship of cigarette smoking to blood pressure and serum lipids and lipoproteins in men. Clin Exp Pharmacol Physiol. 1996;23:397–402. DOI: 10.1111/j.1440-1681.1996.tb02748.x. [DOI] [PubMed] [Google Scholar]
- 9. Primatesta P, Falaschetti E, Gupta S, Marmot MG, Poulter NR. Association between smoking and blood pressure: evidence from the health survey for England. Hypertension. 2001;37:187–193. DOI: 10.1161/01.HYP.37.2.187. [DOI] [PubMed] [Google Scholar]
- 10. Al‐Safi SA. Does smoking affect blood pressure and heart rate? Eur J Cardiovasc Nurs. 2005;4:286–289. DOI: 10.1016/j.ejcnurse.2005.03.004. [DOI] [PubMed] [Google Scholar]
- 11. Patel K, Hargreaves MK, Liu J, Schlundt D, Sanderson M, Matthews CE, Dewey CM, Kenerson D, Buchowski MS, Blot WJ. Relationship between smoking and obesity among women. Am J Health Behav. 2011;35:627–636. DOI: 10.5993/AJHB.35.5.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Perez‐Stable EJ, Herrera B, Jacob P III, Benowitz NL. Nicotine metabolism and intake in black and white smokers. JAMA. 1998;280:152–156. DOI: 10.1001/jama.280.2.152. [DOI] [PubMed] [Google Scholar]
- 13. Berg JZ, Mason J, Boettcher AJ, Hatsukami DK, Murphy SE. Nicotine metabolism in African Americans and European Americans: variation in glucuronidation by ethnicity and UGT2B10 haplotype. J Pharmacol Exp Ther. 2010;332:202–209. DOI: 10.1124/jpet.109.159855. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Ross KC, Gubner NR, Tyndale RF, Hawk LW Jr, Lerman C, George TP, Cinciripini P, Schnoll RA, Benowitz NL. Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking. Pharmacol Biochem Behav. 2016;148:1–7. DOI: 10.1016/j.pbb.2016.05.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Liu X, Byrd JB. Cigarette smoking and subtypes of uncontrolled blood pressure among diagnosed hypertensive patients: paradoxical associations and implications. Am J Hypertens. 2017;30:602–609. DOI: 10.1093/ajh/hpx014. [DOI] [PubMed] [Google Scholar]
- 16. Najem B, Houssiere A, Pathak A, Janssen C, Lemogoum D, Xhaet O, Cuylits N, van de Borne P. Acute cardiovascular and sympathetic effects of nicotine replacement therapy. Hypertension. 2006;47:1162–1167. DOI: 10.1161/01.HYP.0000219284.47970.34. [DOI] [PubMed] [Google Scholar]
- 17. Spohr U, Hofmann K, Steck W, Harenberg J, Walter E, Hengen N, Augustin J, Mörl H, Koch A, Horsch A, et al. Evaluation of smoking‐induced effects on sympathetic, hemodynamic and metabolic variables with respect to plasma nicotine and COHb levels. Atherosclerosis. 1979;33:271–283. DOI: 10.1016/0021-9150(79)90179-5. [DOI] [PubMed] [Google Scholar]
- 18. Krieger N, Sidney S. Racial discrimination and blood pressure: the CARDIA Study of young black and white adults. Am J Public Health. 1996;86:1370–1378. DOI: 10.2105/AJPH.86.10.1370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Scott J, Silva S, Simmons LA. Social adversity, sleep characteristics, and elevated blood pressure among young adult black females. Health Equity. 2020;4:421–429. DOI: 10.1089/heq.2020.0033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Michaels EK, Reeves AN, Thomas MD, Price MM, Hasson RE, Chae DH, Allen AM. Everyday racial discrimination and hypertension among midlife african american women: disentangling the role of active coping dispositions versus active coping behaviors. Int J Environ Res Public Health. 2019;16:4759. DOI: 10.3390/ijerph16234759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Lewis TT, Barnes LL, Bienias JL, Lackland DT, Evans DA, Mendes de Leon CF. Perceived discrimination and blood pressure in older African American and white adults. J Gerontol A Biol Sci Med Sci. 2009;64:1002–1008. DOI: 10.1093/gerona/glp062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Bey GS, Jesdale B, Forrester S, Person SD, Kiefe C. Intersectional effects of racial and gender discrimination on cardiovascular health vary among black and white women and men in the CARDIA study. SSM Popul Health. 2019;8:100446. DOI: 10.1016/j.ssmph.2019.100446. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Udo T, Grilo CM. Cardiovascular disease and perceived weight, racial, and gender discrimination in U.S. adults. J Psychosom Res. 2017;100:83–88. DOI: 10.1016/j.jpsychores.2017.07.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Kendzor DE, Businelle MS, Reitzel LR, Rios DM, Scheuermann TS, Pulvers K, Ahluwalia JS. Everyday discrimination is associated with nicotine dependence among African American, Latino, and White smokers. Nicotine Tob Res. 2014;16:633–640. DOI: 10.1093/ntr/ntt198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Borrell LN, Diez Roux AV, Jacobs DR Jr, Shea S, Jackson SA, Shrager S, Blumenthal RS. Perceived racial/ethnic discrimination, smoking and alcohol consumption in the Multi‐Ethnic Study of Atherosclerosis (MESA). Prev Med. 2010;51:307–312. DOI: 10.1016/j.ypmed.2010.05.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Coronary Artery Risk Development in Young Adults: new investigators. Available at: https://www.cardia.dopm.uab.edu/invitation‐to‐new‐investigators. Accessed January 28, 2021.
- 27. Funkhouser E, Wammack J, Roche C, Reis J, Sidney S, Schreiner P. Where are they now? Retention strategies over 25 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Contemp Clin Trials Commun. 2018;9:64–70. DOI: 10.1016/j.conctc.2017.12.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR Jr, Liu K, Savage PJ. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41:1105–1116. DOI: 10.1016/0895-4356(88)90080-7. [DOI] [PubMed] [Google Scholar]
- 29. Thyagarajan B, Jacobs DR Jr, Apostol GG, Smith LJ, Jensen RL, Crapo RO, Barr RG, Lewis CE, Williams OD. Longitudinal association of body mass index with lung function: the CARDIA study. Respir Res. 2008;9:31. DOI: 10.1186/1465-9921-9-31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Kershaw KN, Robinson WR, Gordon‐Larsen P, Hicken MT, Goff DC Jr, Carnethon MR, Kiefe CI, Sidney S, Diez Roux AV. Association of changes in neighborhood‐level racial residential segregation with changes in blood pressure among black adults: the CARDIA study. JAMA Intern Med. 2017;177:996–1002. DOI: 10.1001/jamainternmed.2017.1226. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Tobin MD, Sheehan NA, Scurrah KJ, Burton PR. Adjusting for treatment effects in studies of quantitative traits: antihypertensive therapy and systolic blood pressure. Stat Med. 2005;24:2911–2935. DOI: 10.1002/sim.2165. [DOI] [PubMed] [Google Scholar]
- 32. Schmitz KH, Jacobs DR Jr, Leon AS, Schreiner PJ, Sternfeld B. Physical activity and body weight: associations over ten years in the CARDIA study. Coronary Artery Risk Development in Young Adults. Int J Obes Relat Metab Disord. 2000;24:1475–1487. DOI: 10.1038/sj.ijo.0801415. [DOI] [PubMed] [Google Scholar]
- 33. Greene SB, Aavedal MJ, Tyroler HA, Davis CE, Hames CG. Smoking habits and blood pressure change: a seven year follow‐up. J Chronic Dis. 1977;30:401–413. DOI: 10.1016/0021-9681(77)90034-0. [DOI] [PubMed] [Google Scholar]
- 34. Choudhary MK, Eraranta A, Tikkakoski AJ, Bouquin H, Hautaniemi EJ, Kahonen M, Sipila K, Mustonen J, Porsti I. Effect of present versus previous smoking on non‐invasive haemodynamics. Sci Rep. 2018;8:13643. DOI: 10.1038/s41598-018-31904-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Lawless MH, Harrison KA, Grandits GA, Eberly LE, Allen SS. Perceived stress and smoking‐related behaviors and symptomatology in male and female smokers. Addict Behav. 2015;51:80–83. DOI: 10.1016/j.addbeh.2015.07.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Chirinos JA, Segers P, Hughes T, Townsend R. Large‐artery stiffness in health and disease: JACC state‐of‐the‐art review. J Am Coll Cardiol. 2019;74:1237–1263. DOI: 10.1016/j.jacc.2019.07.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Levent E, Ozyurek AR, Ulger Z. Evaluation of aortic stiffness in tobacco‐smoking adolescents. J Adolesc Health. 2004;34:339–343. DOI: 10.1016/S1054-139X(03)00302-1. [DOI] [PubMed] [Google Scholar]
- 38. Sassalos K, Vlachopoulos C, Alexopoulos N, Gialernios T, Aznaouridis K, Stefanadis C. The acute and chronic effect of cigarette smoking on the elastic properties of the ascending aorta in healthy male subjects. Hellenic J Cardiol. 2006;47:263–268. [PubMed] [Google Scholar]
- 39. Camplain R, Meyer ML, Tanaka H, Palta P, Agarwal SK, Aguilar D, Butler KR, Heiss G. Smoking behaviors and arterial stiffness measured by pulse wave velocity in older adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Hypertens. 2016;29:1268–1275. DOI: 10.1093/ajh/hpv189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40. Bromfield SG, Sullivan S, Saelee R, Elon L, Lima B, Young AN, Uphoff I, Li L, Quyyumi A, Bremner JD, et al. Race and gender differences in the association between experiences of everyday discrimination and arterial stiffness among patients with coronary heart disease. Ann Behav Med. 2020;54:761–770. DOI: 10.1093/abm/kaaa015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41. Seltzer CC. Effect of smoking on blood pressure. Am Heart J. 1974;87:558–564. DOI: 10.1016/0002-8703(74)90492-X. [DOI] [PubMed] [Google Scholar]
- 42. Savdie E, Grosslight GM, Adena MA. Relation of alcohol and cigarette consumption to blood pressure and serum creatinine levels. J Chronic Dis. 1984;37:617–623. DOI: 10.1016/0021-9681(84)90111-5. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Tables S1–S6