Distinct Component Profiles and High Risk Among African Americans With Metabolic Syndrome

Abstract

Objective

Health of African Americans is seriously threatened by unremitting epidemics of diabetes and cardiovascular disease (CVD). However, the role of metabolic syndrome in the African-American population has not been investigated widely. This study examined the prevalence of metabolic syndrome and assessed its cross-sectional relationship to CVD in the Jackson Heart Study (JHS) cohort.

Research Design and Methods

A total of 5,302 participants aged ≥21 years who were recruited at baseline during 2000–2004 were analyzed for this study. Adjusted odds ratios (ORs) were estimated in a logistic regression analysis for coronary heart disease (CHD) and cerebrovascular disease (CBD) in those with and without coexisting metabolic syndrome. Diabetic participants were excluded.

Results

Among those aged 35–84 years, metabolic syndrome prevalence was 43.3% in women and 32.7% in men. Elevated blood pressure (70.4%), abdominal obesity (64.6%), and low HDL cholesterol (37.2%) were highly prevalent among those with metabolic syndrome. Prevalence rates for CVD, CHD, and CBD were 12.8, 8.7, and 5.8%, respectively. After adjustment for age and sex, metabolic syndrome was associated with increased age- and sex-adjusted ORs for CVD (OR 1.7 [95% CI 1.4–2.1]), CHD (1.7 [1.4–2.2]), and CBD (1.7 [1.3–2.3]) compared with those without CVD, CHD, or CBD.

Conclusion

Metabolic syndrome prevalence in the JHS is among the highest reported for population-based cohorts worldwide and is significantly associated with increased ORs for CVD, CHD, and CBD. Abdominal obesity, increased blood pressure, and low HDL cholesterol (without triglyceride elevation) are surprisingly prominent. A high prevalence of low HDL emerges as a leading contributor to metabolic syndrome among African Americans in this large African-American cohort.

Cardiovascular diseases (CVDs) and diabetes are the most common causes of death and disability in the U.S. and in most developed countries. In the U.S., African Americans have CVD significantly earlier and more often and experience poorer outcomes than their European-American counterparts (1,2). African Americans also have not shared equally in the well-documented national declines in CVD mortality of the past decades (3). Differences in prevalence rates of conventional risk factors as well as socioeconomic factors have been proposed as key elements of the disparities but are not fully explanatory (4 – 6). Although there have been many reports describing the existence of these disparate patterns of CVD, epidemiological study data on factors responsible for these marked differences are limited. Much of the available data relating to CVD risk factors has come from predominantly white populations (7–9).

Metabolic syndrome, a concurrence of several readily measured cardiometabolic characteristics, has become a subject of great interest. It is tightly associated with three major disease epidemics in the U.S.: obesity, type 2 diabetes, and continued high rates of CVD (8,9). According to the definition from the National Cholesterol Education Program (NCEP) Third Adult Treatment Panel Report (ATP III), metabolic syndrome can be defined when three or more metabolic disorders, including abdominal obesity, elevated plasma triglyceride concentration, low plasma HDL cholesterol concentration, elevated blood pressure, and elevated fasting glucose, are present (10). Ford (11) and others (12) reported that the prevalence of metabolic syndrome among U.S. adults significantly increased from 23.1% to nearly 27% during the 1990s decade. They also noted distinct patterns of cardiometabolic risk factors among different ethnic groups in the National Health and Nutrition Examination Survey (NHANES) sample. For instance, African-American men had the highest age-adjusted prevalence of hypertension and African-American women had the highest prevalence of abdominal obesity. Because metabolic syndrome is a significant precursor of CVD (13), the racial/ethnic differences in characteristics and prevalence of metabolic syndrome may help explain some of the ethnic disparity in development of CVD; however, limited information is currently available on the ethnic-specific prevalence of metabolic syndrome and the associated prevalence of CVD in the African-American population. In this study, we examine the prevalence of metabolic syndrome and assess its association with CVD in the Jackson Heart Study (JHS), a large, all African-American, population-based cohort drawn from metropolitan Jackson, Mississippi, the most densely populated region of the state with the highest prevalence of CVD in the nation.

Research Design and Methods

The JHS is a prospective population-based investigation of the predictors and outcomes of CVD and related disorders among African Americans. The original design and sampling plan for the JHS, which have been described in detail previously (14), included only those aged 35–84 years. The current JHS cohort comprises 5,302 participants in total, consisting of 5,036 adults aged 35–84 years and an additional 251 aged 21–34 years and 15 aged >85 years. The latter group entered the study as part of the nested JHS Family Study (15,16). Comprehensive baseline information was obtained. Demographics, socioeconomic status data (e.g., educational attainment and annual household income), multiple lifestyle data (including extensive dietary and physical activity information), and other sociocultural and psychological parameters as well as other interview data were obtained by certified interviewers through home interviews and during the clinic visit. Additionally, certified technicians and nurses conducted clinic interviews and testing that included medical history, anthropometrics, vital signs, venipuncture (for a comprehensive panel of analyses), electrocardiogram (ECG), echocardiography and carotid ultrasonography, and other evaluations.

Samples of glucose and lipids were collected according to standardized procedures and processed at the Central Laboratory (University of Minnesota) described in previous publications (14,15). Sitting blood pressure was measured twice at 5-min intervals; the average of two measurements was used for analysis. Two measures of the waist (at the level of the umbilicus and in the upright position) were averaged to determine baseline waist circumference for each participant. For the present analysis, we excluded individuals who did not complete data collection on any components of metabolic syndrome.

Criteria for metabolic syndrome

The ATP III has identified five components of metabolic syndrome that related to CVD (abdominal obesity, high triglyceride concentration, low HDL cholesterol concentration, elevated blood pressure, and elevated fasting glucose concentration) (10). In consonance with the ATP III definition, the subjects were considered to have metabolic syndrome if they had three or more of following: 1) abdominal obesity, defined by waist circumference ≥ 102 cm (40 inches) in men and ≥ 88 cm (35 inches) in women; 2) elevated blood pressure, defined as a systolic blood pressure of 130 mmHg or greater and/or a diastolic blood pressure of 85 mmHg or greater, physician diagnosis, and/or use of antihypertensive drugs; 3) elevated plasma triglyceride concentration (≥150 mg/dl) or treatment with fibrate medication; 4) Low HDL cholesterol concentration (men <40 mg/dl and women <50 mg/dl); and 5) elevated fasting glucose concentration (≥100 mg/dl) or diagnosed type 2 diabetes. Only individuals who contributed fasting blood specimens, with exception of those under treatment for type 2 diabetes, were included in this report.

Definition of coronary heart disease, cerebrovascular disease, and CVD

Prevalent coronary heart disease (CHD) was defined as evidence of a previous myocardial infarction by ECG based on Minnesota Code criteria (Codes 1.1 and 1.2 plus 4.1–4.2, or 5.1–5.2), a history of physician-diagnosed myocardial infarction, or either percutaneous coronary intervention or coronary bypass surgery. Cerebrovascular disease (CBD) was defined as a history of CBD (by personal history, CBD signs and symptoms ascertained by standardized questionnaires), transient ischemic attack, or carotid endarterectomy and/or angioplasty. CVD was defined as having either CHD or CBD. All medical history obtained at baseline was self-reported.

Reference group

To determine the cross-sectional association of metabolic syndrome with morbid vascular conditions, we calculated the odds of prevalent cardiovascular disease manifestations (CHD, CBD, and CVD) in those with metabolic syndrome compared with the reference group, defined as participants who did not have metabolic syndrome.

Education, annual income, alcohol, and smoking

Educational attainment was divided into four categories: less than high school education), high school or GED, more than high school but less than college, and college or greater. Annual incomes were divided into five categories according to the participant's household income for the previous year: <$16,000, $16,000 – 24,999, $25000 – 49,999, $50,000 – 99,999, and >$100,000. Alcohol consumption and cigarette smoking were analyzed as current practice (self-reported as user in past 12 months versus nonuser).

Statistical methods

Data were analyzed using the SAS system for Windows, version 9.1 (SAS Institute, Cary NC). Contingency tables were compiled to calculate the sample prevalence of metabolic syndrome and its possible components (elevated blood pressure, abdominal obesity, low HDL cholesterol, and elevated glucose and triglyceride concentrations). Prevalence was calculated separately for age, sex, current alcohol consumption and smoking status, marital status, education, and annual household income. The χ² test was performed to assess the significance of subgroup differences.

To assess the prevalence of each metabolic component, age- and sex-specific prevalence for each metabolic component was calculated separately from the entire JHS cohort. Logistic regression models were used to calculate odds ratios (ORs) and their 95% CI to assess the odds of CVD, CHD, and CBD being present in a participant with metabolic syndrome versus in a participant without metabolic syndrome. Statistical tests of hypothesis with two-directional alternatives that resulted in P ≤ 0.05 were considered statistically significant.

Results

Baseline prevalence of metabolic syndrome

The prevalence of metabolic syndrome in baseline JHS participants is summarized in Table 1. The overall (aged 21–94 years) prevalence of metabolic syndrome in the JHS cohort was 39.4%. Large percentages of participants with metabolic syndrome were found to have elevated blood pressure (70.4%), abdominal obesity (64.6%), and low HDL cholesterol concentration (37.2%). Among those aged 35–84 years, the age-adjusted prevalence was 44.8% in women and 33.4% in men (P < 0.0001) (Table 2). Women with metabolic syndrome had a comparatively higher prevalence of abdominal obesity and low HDL cholesterol concentration than men (P < 0.0001 for both comparisons).

Table 1. Prevalence of metabolic syndrome and individual metabolic factors by age and sex in the JHS cohort, 2000–2004.

	Subjects (n)	Metabolic syndrome	Elevated blood pressure	Abdominal obesity	Low HDL cholesterol	Elevated glucose	Elevated triglyceride
Age (Pdiff)		<0.0001	<0.0001	<0.0001	NS	<0.0001	<0.0001
Overall	4,706	39.4	70.4	64.6	37.2	29.7	16.6
21–34 years	236	16.5	24.6	51.7	44.9	6.8	9.8
35–44 years	911	25.4	48.7	58.7	40.3	13.9	11.3
45–54 years	1,169	36.4	66.3	64.8	38.9	22.4	16.2
55–64 years	1,277	48.2	81.7	67.3	35.4	40.8	19.7
65–74 years	845	50.2	89.1	70.4	33.3	43.2	19.4
75–84 years	244	45.5	88.5	64.3	34.1	38.5	18.4
85+ years	15	33.3	93.3	53.3	13.3	46.7	13.3
Sex (Pdiff)		<0.0001	NS	<0.0001	<0.0001	NS	<0.0001
Female	2,998	43.3	70.7	76.5	39.5	29.6	14.5
Male	1,708	32.7	69.9	43.7	33.1	29.9	20.1

Individuals taking diabetic medication or with fasting glucose level > 126 mg/dl excluded from analysis.

Table 2. Prevalence of metabolic syndrome and individual metabolic factors by socioeconomic status, smoking, and alcohol consumption in participants aged 35–84 in the JHS Cohort, 2000–2004.

	Subjects (n)	Metabolic syndrome	Elevated blood pressure	Abdominal obesity	Low HDL cholesterol	Elevated glucose	Elevated triglyceride
Sex (Pdiff)	4,455	<0.0001	NS	<0.0001	<0.0001	NS	<0.0001
Female (aged 35–84 years)	2,848	44.8	73.1	77.1	39.2	30.7	15.0
Male (age 35–84 years)	1,607	33.4	72.0	44.4	32.7	31.1	20.4
Education (Pdiff)	4,437	<0.0001	<0.0001	<0.0001	NS	<0.0001	0.0380
< high school	795	50.6	84.7	69.8	36.0	42.5	18.5
High school or GED	876	42.4	76.6	68.2	36.3	32.7	16.4
> high school but < BS	1,276	38.5	67.9	65.3	38.3	28.5	18.5
BS or higher	1,490	36.2	68.3	61.4	36.3	25.4	14.8
Income (Pdiff)	3,808	<0.0001	<0.0001	<0.0001	NS	<0.0001	NS
<$16,000	815	50.1	81.2	73.6	36.1	40.0	18.7
$16,000–24,900	575	44.5	77.2	70.1	36.5	34.1	17.7
$25,000–49,999	1,066	40.3	73.1	66.3	35.8	30.6	17.3
$50,000–99,999	1,031	34.4	66.3	58.5	37.0	25.3	15.1
>$100,000	321	31.2	62.9	52.7	35.5	24.0	14.0
Smoking status (Pdiff)	4,423	NS	NS	<0.0001	0.0159	NS	<0.0001
Not current	3,860	41.2	73.1	67.1	36.1	31.3	16.1
Current smoker	563	38.2	70.1	53.8	41.4	27.5	22.7
Alcohol use (Pdiff)	4,437	<0.0001	<0.0001	<0.0001	<0.0036	<0.0001	NS
Not current	2,854	45.4	77.4	70.3	38.8	34.3	17.1
Current drinker	2,418	34.8	67.0	59.1	34.5	26.6	16.7

For the cohort as a whole, prevalence of elevated blood pressure, abdominal obesity, and elevated triglyceride and glucose levels increased with age whereas low HDL cholesterol concentration was about equally prevalent across all age-groups. The prevalence of elevated triglyceride and low HDL cholesterol concentrations were significantly higher in smokers compared with nonsmokers. In addition, participants with higher educational attainment and household income and absence of alcohol consumption have lower prevalence of metabolic syndrome, elevated blood pressure, abdominal obesity, and elevated glucose levels (Table 2).

Metabolic syndrome and prevalent CHD, CBD, and CVD

The prevalences of CVD, CHD, and CBD among those with metabolic syndrome were 12.8, 8.7, and 5.8%, respectively. In logistic regression analyses adjusted for age and sex, metabolic syndrome–associated ORs for prevalent CVD, CHD, and CBD were about 1.7 (Table 3).

Table 3. OR and 95% CI for CHD, CBD, and CVD with or without coexisting metabolic syndrome in the JHS cohort aged 35–84 years.

	CVD	CHD	CBD
n	422	283	187
Prevalence (%)	12.8	8.7	5.8
OR (95% CI)	1.7 (1.4–2.1)	1.7 (1.3–2.2)	1.7 (1.3–2.3)
Women
Prevalence (%)	11.5 (n = 235)	7.3 (n = 150)	5.6 (n = 110)
OR (95% CI)	1.7 (1.3–2.2)	1.6 (1.1–2.2)	1.9 (1.3–2.8)
Men
Prevalence (%)	16.0 (n = 187)	12.0 (n = 133)	6.4 (n = 77)
OR (95% CI)	1.7 (1.2–2.3)	1.8 (1.3–2.7)	1.5 (0.9–2.4)

OR is adjusted for age and sex.

Conclusions

Prevalence of metabolic syndrome

The prevalence of metabolic syndrome reported by different studies in the U.S. has varied widely. Differences in the characteristics of study populations, the definition of metabolic syndrome, study geographic locations, and study time periods have all contributed to this variation. Data from population-based cohorts such as the Framingham Offspring Study and San Antonio Heart Study during the early to mid-1990s reported high prevalence estimates (24 and 30%, respectively) among participants who did not have diabetes (12). Baseline data (obtained 1987–1989) from the Atherosclerosis Risk in Communities Study indicated that the prevalence of metabolic syndrome was 28% in African-American men, 18% in women, and 30% overall in a middle-aged cohort (17). During 1988–1994, NHANES III (a national probability sample) using NCEP ATP III criteria showed that the unadjusted prevalence of metabolic syndrome was 21.8% among the U.S. general population (11). More recently, NHANES III, using consistent sampling methodology and case definition, found a prevalence of 26.7% in the year 2000 (18). Increases in the prevalence of obesity and hypertension and to a lesser degree in hypertriglyceridemia and low HDL cholesterol concentration most likely accounted for much of this increase (18).

Our analyses of recently obtained (2000–2004) baseline data from JHS, the largest population-based epidemiological study of CVD in African Americans ever undertaken, demonstrate extraordinarily high metabolic syndrome prevalence and typical component profiles compared with the general metabolic syndrome literature. Among those aged 35–84 the prevalence was 44.8% in women and 33.4% in men, far above corresponding national rates. The prevalence of metabolic syndrome is significantly and inversely associated with socioeconomic status and is higher in women than in men at similar degrees of education and socioeconomic status. Both in men and women, the prevalence significantly decreases with increases in household income and educational attainment.

Although limited data are available regarding the prevalence of various metabolic syndrome profiles in the African-American population, our study suggests that African Americans may have distinct cardiometabolic risk patterns within the rubric of metabolic syndrome. In studies examining differences in prevalence of metabolic syndrome profiles, abdominal obesity, elevated blood pressure, and elevated triglyceride concentration predominated as metabolic syndrome components in European and Mexican Americans (11,19–22). Among the JHS cohort, however, elevated blood pressure, abdominal obesity, and low HDL cholesterol concentration were more frequent than the triad of conditions most commonly seen in metabolic syndrome among other groups. The higher frequency of low HDL cholesterol concentration is notable for at least two reasons. First, owing to a multitude of studies that have reported high HDL cholesterol concentration for African Americans, there is a prevailing notion that low HDL cholesterol concentration is relatively uncommon among African Americans (11,23,24). However, NHANES highlighted the fact that the race-specific rates of low HDL cholesterol have risen among African Americans from 1989–1994 to 1999–2000 (11,25). Our data seem to reflect this trend. Second, the usual reciprocal elevation in triglyceride concentration that accompanies low HDL cholesterol is not evident and the prevalence of a low HDL cholesterol level stays high across age spectra in our cohort. This finding seems to corroborate indirectly the findings of the Triglyceride and Cardiovascular Risk in African American (TARA) Study of the National Institutes of Health, which reported that insulin-resistant African-American subjects do not demonstrate impairment of postheparin–lipoprotein lipase activity commonly seen with insulin resistance in other ethnic groups. This impairment is inversely associated with serum triglyceride concentration (26). A low frequency of impairment of postheparin–lipoprotein lipase in African Americans with metabolic syndrome (and presumed insulin resistance) would help explain why triglyceride levels remain low, even in a population with high rates of depressed HDL cholesterol levels. This finding could explain our observation that triglyceride concentration abnormalities contribute little to the prevalence of metabolic syndrome in this African-American cohort. In addition, it is worthy to note that the prevalence of metabolic syndrome tends to be lower in current smokers, whose triglyceride level is elevated and HDL cholesterol concentration is depressed. Alcohol drinking also was associated with a lower prevalence of metabolic syndrome with decreased prevalence of low HDL cholesterol concentration. These findings are generally consistent with the expected and widely replicated inverse association of HDL and smoking. The positive association of triglyceride concentration and smoking has also been reported. In contrast, the lower prevalence of metabolic syndrome in those who are not current drinkers suggests that drinking may have modest differential influences on the individual metabolic syndrome components.

Recently, the concept of the metabolic syndrome has been challenged on several fronts. Variation in its definition by different professional and scientific bodies (27), ethnic specificity of some component cut points (28), and the additive rather than synergistic impact of risk factors on CVD outcomes (29) have led to controversy in assigning the label “syndrome” to this grouping of metabolic abnormalities. NCEP ATP III does not mandate any specific metabolic component as a necessary condition for the diagnosis of metabolic syndrome. This issue is controversial, however, and data suggesting that a common antecedent or underlying perturbation in metabolic function produces the syndrome have been reported (30). In the JHS cohort, although elevated blood pressure, abdominal obesity, and low HDL cholesterol concentration are particularly prevalent in metabolic syndrome, the frequency of elevated glucose is still substantial both in men and women, indicating that hyperglycemia is also an important contributor to metabolic syndrome prevalence. This result is consistent with the fact that insulin resistance is the core pathological feature of the metabolic syndrome (31), a notion further supported by other studies (29, 32).

Metabolic syndrome and CVD disparities

Growing evidence for metabolic syndrome as a major cause for both diabetes and CVD raises the question of whether differences in metabolic syndrome prevalence and/or profiles between African and European Americans might help explain racial disparities in the prevalence of diabetes and cardiovascular complications. Although our study does not permit a direct cross-racial comparison, the facts that the JHS cohort demonstrated a high prevalence of CHD, CBD, and overall CVD and the presence of metabolic syndrome increased the odds of these diseases are substantially comparable to the > 1.6-fold increase in risk found by others (21,23). Our demonstration of high OR and higher prevalence suggest a high attributable risk in the African-American population for metabolic syndrome. This finding further suggests that control/elimination of metabolic syndrome would result in a substantial reduction in manifest CVD among African Americans.

We also found that the risk for CVD attributable to these cardiometabolic abnormalities is greater in women than in men. Recent mortality data from the San Antonio Heart Study demonstrated that the association between metabolic syndrome and CVD death was more than twice as large in women as in men (33). The authors suggested that a possible explanation for this difference is the stronger diabetes-CVD association in women. In the JHS, increased prevalence of metabolic syndrome in women was associated with their greater proportion of abdominal obesity and low HDL cholesterol concentration. This result could reflect a sex-specific impact of obesity on glucose homeostasis, lipid profiles, and atherosclerosis (34).

Limitations of study

The principal limitation of this analysis is the use of cross-sectional data, necessitated by the use of the initial data from this new cohort. Thus, causal pathways underlying the observed relationships cannot be inferred. Also, owing to the design of the initial JHS examination used for this analysis, we relied significantly, although not exclusively, on self-reported medical history data. Although CBD history was obtained exclusively by self-report, the CHD definition (and consequently the CVD definition) combined self-reported data with ECG findings for corroboration and additional case ascertainment (e.g., “silent myocardial infarction”). Another limitation of this analysis is that we were not able to fully account for all potential covariates, such as changes in physical activity, dietary information, and weight gain. Therefore, future research should investigate the impact of these covariates, especially dietary and fitness differences among the participants with or without metabolic syndrome.

Although not a limitation specific to this analysis, it should be noted that the NCEP ATP III cut points for abnormal HDL and triglyceride concentration may lead to an underestimation of metabolic risk among African Americans. As noted above, at least one prior investigation indicated that African Americans, despite being more insulin resistant than their European-American counterparts, paradoxically exhibited lower triglyceride and higher HDL cholesterol concentrations (35). This finding suggests that applying a uniform cut point for both groups for triglyceride and HDL cholesterol concentrations may result in significant misclassification (36). Adjustment of cut point values (using CVD incidence data by triglyceride and HDL concentrations) or measures of lipoprotein subclass profiles (e.g., VLDL, small LDL, and HDL particle concentrations) may provide better estimates of lipid-related metabolic risk in African Americans than sole use of the lipid criteria from the NCEP ATP III (26). However, our data affirm that abdominal obesity, elevated blood pressure, and low HDL cholesterol concentration are key components of metabolic syndrome in the African-American population.

Abbreviations

ATP III

Third Adult Treatment Panel Report

CBD

cerebrovascular disease

CHD

coronary heart disease

CVD

cardiovascular disease

ECG

electrocardiogram

JHS

Jackson Heart Study

NCEP

National Cholesterol Education Program

NHANES

National Health and Nutrition Examination Survey