The role of obesity as an independent risk factor for

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1 AJH 2002; 15: The Relationship Between Body Mass Index and Pulse Pressure in Older Adults With Isolated Systolic Hypertension David Martins, Naureen Tareen, Deyu Pan, and Keith Norris Background: Many longitudinal studies have reported excess cardiovascular mortality among lean hypertensive subjects, suggesting that obesity may mitigate the cardiovascular risk of hypertension. Available evidence also suggests that in middle-aged and older hypertensive subjects, pulse pressure may be a better predictor of cardiovascular complications. However, there are limited data on the relationship between body mass index (BMI) and pulse pressure. Methods: Using data from the Third National Health and Nutrition Examination Survey we assessed the convergence validity of pulse pressure as a predictor of cardiovascular complications and examined the relationship between BMI and pulse pressure in 1192 older adults with isolated systolic hypertension who were not receiving blood pressure medicine. Results: There was a good concordance between high pulse pressure and most of the selected cardiovascular risk factors examined in this study. Pulse pressure is higher in the lean (BMI 25) than in the overweight (BMI 25; 79 mm Hg vs 74 mm Hg, P.001) and decreases significantly from 82 mm Hg in the first BMI quintile to 76 mm Hg in the fifth BMI quintile. Pulse pressure continues to decrease with increasing BMI until the index exceeds This negative correlation persists in a multivariate model with statistical adjustment for age, sex, diabetes mellitus, and hypercholesterolemia. Conclusion: The inverse relation between BMI and pulse pressure observed here may help to explain previous reports of increased cardiovascular risk among lean versus obese subjects with isolated systolic hypertension. Am J Hypertens 2002;15: American Journal of Hypertension, Ltd. Key Words: Obesity, overweight, elderly, body mass index, pulse pressure. The role of obesity as an independent risk factor for cardiovascular mortality is controversial. 1,2 Many longitudinal studies have reported excess cardiovascular mortality among lean hypertensive subjects. 3 5 It has been suggested that obesity may mitigate the cardiovascular risk of hypertension. 6 8 Although the relative risk of death associated with obesity decreases with age, 9 11 studies are few on the effect of obesity on cardiovascular morbidity in older patients with isolated systolic hypertension (ISH). A low body mass index (BMI) was associated with increased risk of death and stroke in the Systolic Hypertension in the Elderly Program. 12 Available evidence also suggests that in middle-aged and older hypertensives pulse pressure may be a better predictor of cardiovascular complications The relationship between BMI and pulse pressure is unclear. An understanding of the relationship between BMI and pulse pressure in older adults with ISH will be valuable to clarify further the effect of obesity on cardiovascular risk. In this study we examined the relationship between BMI and pulse pressure in a population of older adults with ISH using data from the Third National Health and Nutrition Examination Survey (NHANES III). Methods The NHANES III is a study of a representative sample of the civilian, noninstitutionalized population of the United States that is conducted periodically by the National Center for Health Statistics. The survey is designed to estimate Received December 11, First Decision November 1, Accepted January 15, From the Department of Internal Medicine (DM, NT, DP, KN) at King Drew Medical Center, Los Angeles, California, and University of California (KN), Los Angeles, California. This research was supported by the Research Centers in Minority Institutions Awards P20-RR11145 and G12RR from the National Center for Research Resources, National Institutes of Health, Bethesda, Maryland. This article was presented as an abstract for the Poster presentation at the Sixteenth Annual Scientific Meeting of the American Society of Hypertension, May 15 19, 2001, San Francisco, California. Address correspondence and reprint requests to Dr. Keith Norris, Professor and Vice-Chair, Department of Internal Medicine, King Drew Medical Center, South Wilmington Avenue, Los Angeles, CA 90059; knorris@ucla.edu /02/$ by the American Journal of Hypertension, Ltd. Downloaded from PIIhttps://academic.oup.com/ajh/article-abstract/15/6/538/ S (02) Published by Elsevier Science Inc.

2 AJH June 2002 VOL. 15, NO. 6 BODY MASS INDEX AND PULSE PRESSURE 539 the prevalence of common chronic conditions and associated risk factors for disease control and prevention. NHANES III was conducted from 1988 to The sample for the survey was obtained through a complex multistage cluster design with over-sampling of persons aged 60 years and those of non-hispanic African American and Mexican American ethnicity to enhance the precision of prevalence estimates in these groups. 17 The survey commences with a 1-h home visit for a household interview during which information on demography, socioeconomic status, medical history, nutrition history, and family history was obtained by trained interviewers and recorded in the data collection form. 18 A set of three blood pressure (BP) measurements was obtained at the end of the interview. The interview is followed a few weeks later by a 4-h physical examination at a mobile examination center. The physician obtained a second set of three BP measurements during this examination. All BP measurements were done in the sitting position after 5 min of rest by certified observers using the standard mercury sphygmomanometer, with strict adherence to the American Heart Association recommendations for human BP measurement. 19 All available systolic and diastolic BPs were averaged for each individual participant. Isolated systolic hypertension (ISH) was defined as a mean systolic BP 140 mm Hg, and mean diastolic BP as 90 mm Hg. 20 Data Analysis The sample for this analysis consisted of the 624 female and 568 male participants in NHANES III who were aged 55 years, were considered to have ISH, and were receiving no BP medications. Body mass index was calculated for the participants from their recorded weight (in kilograms) and height (in meters) using the expression Weight/Height 2. Based on the revised guidelines from the National Center for Health Statistics, 21 the participants were classified as lean or overweight according to a BMI 25 or 25, respectively. Pulse pressure was deduced from the difference of the means of all recorded systolic and diastolic BPs. The degree of concordance between pulse pressure and selected cardiovascular risk factors was examined by analysis of variance in univariate models to assess the validity of pulse pressure as a determinant of cardiovascular risk in older patients with ISH. The relationship between pulse pressure, systolic BP, and BMI was examined in the overall sample and among men and women by a plot of pulse pressure and systolic BP against BMI groupings. In a separate analysis we compared the mean pulse pressure in the lean and overweight participants and within BMI quintiles. The independence of the relationship between BMI and pulse pressure was established in multivariate analysis with statistical adjustment for the effects age, sex, diabetes mellitus, hypercholesterolemia, and cigarette smoking as potential confounders. Two-sided t test of significance was applied to the difference in mean pulse Table 1. Distribution of selected cardiovascular risk factors among lean and overweight participants in analysis sample Cardiovascular Risk Factor Body Mass Index <25 >25 Total (%) Age, years (22.0%) (32.6%) (32.6%) (12.8%) Sex Male (47.7%) Female (52.5%) Diabetes mellitus Nondiabetic (85.3) Diabetic (14.7%) Hypercholesterolemia 250 mg/dl (70.2%) 250 mg/dl (29.8%) Smoking Nonsmoker (48.8%) Smoker (51.6%) Overall (100%) Some groups may not total exactly 100% because of rounding. pressure between groups in all univariate analyses and a value of P.05 considered to be significant. Results Study Sample The study included 1192 participants (624 women and 568 men) who were aged 55 years, had ISH, and were receiving no BP medications. The characteristics of the analysis sample are as shown in Table 1. There were more overweight participants in most of the age categories except in the group aged 85 years. Most subjects in the group aged 55 to 64 years were overweight, but very few subjects aged 85 years were overweight. More overweight than lean participants reported a history of diabetes mellitus, admitted to smoking 100 cigarettes during their lifetimes, and had cholesterol levels 250 mg/dl. Analysis There was a good concordance between pulse pressure and the selected cardiovascular risk factors examined with the exception of smoking (Table 2). Both BP and pulse pressure decreased with increasing BMI, but this decrease slowed when BMI was 25 and reversed when BMI was 30.1 (Fig. 1). Overall, pulse pressure was higher in the women than in the men among the lean and the overweight participants, but there were noteworthy differences in the relationship between BMI and pulse pressure among men and women (Fig. 2). The difference in pulse pressure between lean male and female participants was not statistically significant (P.07), but between overweight male

3 540 BODY MASS INDEX AND PULSE PRESSURE AJH June 2002 VOL. 15, NO. 6 Table 2. Association of mean pulse pressure with selected cardiovascular risk factors Cardiovascular Risk Factor Mean Pulse Pressure (SD) mm Hg P Value Between Groups Age, years 55 64* (13.60) (12.76) (16.37) (14.78).001 Sex Male (13.22) Female (16.29).001 Diabetes mellitus Nondiabetic (14.70) Diabetic (16.60).001 Hypercholesterolemia 250 mg/dl (17.03) 250 mg/dl (18.85).001 Smoking Nonsmoker (18.38) Smoker (16.79).001 * Reference group for comparison among age categories. Number of participants who report smoking decreases from youngest to oldest age category. and female participants was statistically significant (P.001). Also, the difference in pulse pressure between lean and overweight male participants was statistically significant (P.001) but between lean and overweight female participants was not (P.15). Mean pulse pressure also decreased significantly by approximately 6 mm Hg from mm Hg in the first quintile to mm Hg in the fifth quintile (Table 3). The decrease in pulse pressure with increasing BMI was much greater from the first to the third quintile than from the third to the fifth quintile. There was a negative correlation between BMI and pulse pressure in a multivariate model with statistical adjustment for age, sex, diabetes mellitus, and hypercholesterolemia (Table 4). Discussion The NHANES III data derives from a representative sample of the United States population and provides some of the best available estimates of the prevalence and treatment of hypertension in the United States. Multiple BP measurements by trained and certified observers using a standardized protocol enhance the accuracy of the BP data in NHANES III. The over-sampling of participants aged 60 years in the complex multistage cluster design of the survey makes it very suitable for the purposes of our study. The selection of participants aged 55 years with ISH for analysis in this study increases the probability of isolating the relationship between BMI and pulse pressure. The decline in diastolic BP responsible for the increase in pulse pressure with age is more marked in patients after 50 years of age. 22 The exclusion of participants on medications for high BP from this study removes any confounding effect of high BP medication on the selection of participants with isolated systolic hypertension. The higher prevalence of diabetes mellitus and hypercholesterolemia among the overweight participants in this study is consistent with reports in the literature. 23 Both cross-sectional studies and prospective studies have reported an association between obesity and hypertension. 24,25 However, there are some exceptions, and the correlation between BP and body weight in several of these studies is at best modest, indicating that there may be FIG. 1. Relationship between systolic blood pressure (SBP), pulse pressure (PP), and body mass index (BMI) in study subjects.

4 AJH June 2002 VOL. 15, NO. 6 BODY MASS INDEX AND PULSE PRESSURE 541 FIG. 2. Mean pulse pressures and body mass index among male and female participants in the study. Table 3. Mean pulse pressure by body mass index subgroupings Body Mass Index Mean Pulse Pressure (SD), mm Hg P Value Lean v overweight 25* 78.96(13.77) (12.46) Body mass index quintiles 22.2* (14.81) (16.46) (13.41) (14.09) (15.45) * Reference group for comparison. factors that modify the risk of hypertension in obesity. 26 In fact, the correlation between BP and body weight decreases significantly after age 60 years in most of these prospective studies, 27 and the result of our analysis of the relationship between systolic BP and BMI is consistent with these findings. The higher pulse pressure observed among nonsmokers in this study may be attributed, in part, to a higher prevalence of smoking among the younger subset of participants, as well as to the tendency for pulse pressure to increase with advancing age. This view is supported by the fact that the number of participants who reported smoking decreased from the youngest to the oldest age category and by the loss of the effect of smoking in multivariate analysis. Several factors including age ( 60 years), sex (men and postmenopausal women), diabetes mellitus, and dyslipidemia have been identified as major risk factors for cardiovascular disease. 20 Available evidence also suggests that pulse pressure may be a better predictor of cardiovascular complications, particularly in middle-aged and older subjects with hypertension. 13 Our results lend additional support to the role of pulse pressure as a predictor of cardiovascular outcomes in older persons with hypertension. Several studies that have examined the relationship between body weight and cardiovascular mortality report a curvilinear relationship with increased risk of mortality among the very lean and very overweight The level at which obesity assumes morbid and prognostic significance is not easy to define, and the effect of sex on Table 4. Results of the multivariate analysis of the relationship between pulse pressure and body mass index Independent Variable* (SE) P Value Age 0.51 (0.046).001 Sex 3.85 (0.92).001 Diabetes mellitus 5.48 (1.16).001 Body mass index 1.25 (0.59).036 Hypercholesterolemia 1.82 (0.90).044 Smoking 0.77 (0.90) ns ns not significant. * Pulse pressure is the dependent variable.

5 542 BODY MASS INDEX AND PULSE PRESSURE AJH June 2002 VOL. 15, NO. 6 morbidity associated with obesity is difficult to establish. There are reports that the relative risk of death associated with obesity decreases with advancing age, suggesting that the optimal weight for longevity may be higher in older persons. 9,11,28 The statistically significant higher pulse pressure that we observed in the lean male participants is consistent with the excess cardiovascular mortality reported in lean hypertensive men from the Hypertension Detection and Follow-up Program. 5 In fact, past weight guidelines did recommend higher maximal weight for height with increasing age, 31 but the present guidelines make no age-specific recommendations. 21 The pulse pressure results from our study seem to suggest that the optimal weight for longevity may be higher in older persons with ISH. A change in BMI from 32.3 to 27.6 was associated with an increase in large arterial distensibility in men between age 18 and 50 years. 32 Interestingly, the change in BMI reported in the latter study occurred across the BMI level at which the favorable effect of increasing BMI is lost in our study. More prospective studies in older patients over a wider range of BMI are needed to define better the level at which obesity assumes morbid and prognostic significance, particularly in the elderly. Several factors limit the findings from this study. The NHANES III is a cross-sectional data set from which a causal inference cannot be drawn. Body mass index, which was used in this study, may be a less sensitive indicator of adiposity in elderly individuals, in whom fat has been shown to shift from peripheral to central sites, thereby increasing waist-to-hip ratio and its associated risk of cardiovascular mortality without changing BMI. 33 The positive correlation between BMI and diabetes mellitus 34 and the association of diabetes mellitus with arterial stiffening 35 may account for the higher pulse pressure observed in participants with BMI The relationship between BP, body weight, and age is complex and controversial. Despite these limitations, however, we believe that our findings provide further insight into the role of pulse pressure as a predictor of cardiovascular outcomes in the elderly with ISH. 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