Burden of subclinical cardiovascular disease in “metabolically benign” and “at-risk” overweight and obese women: The Study of Women's Health Across the Nation (SWAN)

doi:10.1016/j.atherosclerosis.2011.01.007

Atherosclerosis

Volume 217, Issue 1, July 2011, Pages 179-186

https://doi.org/10.1016/j.atherosclerosis.2011.01.007 Get rights and content

Abstract

Background

Metabolically benign obese individuals have a 10-year cardiovascular disease (CVD) risk comparable to healthy normal weight individuals. However, the burden of subclinical CVD among metabolically benign obese is not well known.

Methods

In cross-sectional analyses of 475 mid-life women, we compared common carotid artery intima media thickness (CCA-IMT), aortic pulse wave velocity (aPWV) and coronary (CAC) and aortic calcification (AC) among three groups: healthy normal weight, metabolically benign overweight/obese (<3 metabolic syndrome components/elevated CRP), and at-risk overweight/obese (≥3 metabolic syndrome components/elevated CRP).

Results

The mean (SD) CCA-IMT and aPWV were lowest in the normal weight group (n = 145), followed by the benign overweight/obese (n = 260) and at-risk overweight/obese (n = 70) groups [CCA-IMT: 0.64 (0.08) vs. 0.68 (0.09) vs. 0.73 (0.13) mm, p < 0.001; aPWV: 731.0 (176.4) vs. 809.9 (182.3) vs. 875.7 (228.8) cm/s, p < 0.001]. Similar results were found for the frequency (%) of women with increased CAC and AC [CAC: 13 (9%) vs. 53(20%) vs. 28(40%), p < 0.001; AC: 47(32%) vs. 130 (50%) vs. 55(79%), p < 0.001]. These differences remained significant after multivariable adjustment. Further adjustment for BMI attenuated the statistical significance of differences in aPWV and calcification between benign and at-risk overweight/obese women, but had little effect on the magnitude of these differences.

Conclusions

Metabolically benign overweight/obese women have a significantly greater subclinical CVD burden than normal weight women, despite published data finding similar CVD event rates between the two groups. Prospective studies tracking the progression of subclinical atherosclerosis to clinical CVD in these women are needed.

Introduction

There is growing recognition of the heterogeneity in cardiovascular disease (CVD) risk in obese individuals. Multiple studies have identified a metabolically benign obese phenotype that fulfills the criteria of clinical obesity by BMI or waist circumference, but does not have the burden of adiposity-associated cardiometabolic risk factors found among those with the “at-risk” obese phenotype [1], [2], [3], [4] Longitudinal studies have found a similar prevalence of CVD events over 3–11 years between those with metabolically benign obesity (defined in these publications as the absence of metabolic syndrome and diabetes) and normal weight individuals, in contrast to the elevated CVD risk found in at-risk obese individuals [1], [2], [5]. However, recent analyses from the Health Professional's Follow-Up Study of men and the Nurse's Health Study of women demonstrate a 40–200% increased risk of CVD in overweight and obese men and women followed for 16 years [6] These most recent findings raise the possibility that individuals with metabolically benign obesity do have an increased risk of incident CVD compared to normal weight individuals, but experience a delay in the onset of clinical CVD compared to their at-risk counterparts. If this hypothesis were true, it might be expected that metabolically benign obese individuals would have a greater burden of subclinical CVD compared to healthy normal weight individuals, but a lesser subclinical CVD burden compared to at-risk obese individuals. Few studies have examined the burden of subclinical CVD in different body size phenotypes, and have used insulin resistance to define benign vs. at-risk phenotypes [3], [7] rather than definitions comparable to those used in the clinical CVD event literature.

The purpose of the current study was to compare the subclinical CVD burden in metabolically benign overweight/obese women compared to normal weight women and at-risk overweight/obese women participating in the Study of Women's Health Across the Nation Heart ancillary study using phenotype definitions similar to those used in the clinical CVD event literature.

Section snippets

Study population

The current study included participants from the Study of Women's Health Across the Nation (SWAN). SWAN is a multicenter, multiethnic longitudinal study designed to characterize the biological and psychosocial changes that occur during the menopausal transition in a community-based sample. Details of the study design and recruitment have been previously published [8]. Briefly, SWAN is being conducted at seven sites: Boston; Chicago; the Detroit area; Los Angeles; Newark, NJ; Pittsburgh, PA; and

Results

Of the 475 women with complete data on both CCA-IMT and aPWV, 31% were normal weight, 55% were in the benign overweight/obese group and 15% were in the at-risk overweight/obese group. Comparing the three body size phenotypes (Table 1), there were no statistically significant differences in education or menopause status. The at-risk overweight/obese was significantly older than the normal weight and the benign overweight/obese phenotypes. A lower percentage of African American women were in the

Discussion

Reports of CVD events have indicated that compared to normal weight individuals, metabolically benign overweight/obese individuals are not at increased 3–11 year risk of CVD [1], [2], but are at increased 16-year risk of CVD [6]. In our midlife women, we found that compared to normal weight women, women with metabolically benign overweight/obesity had a greater burden of subclinical CVD. This was reflected by higher levels of CCA-IMT and aPWV and a greater prevalence of coronary and aortic

Conflicts of interest

The authors have no conflicts of interest to report in relation to the work described in this manuscript.

Acknowledgments

The Study of Women's Health Across the Nation has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The SWAN Heart Study is supported by the National Heart, Lung, and Blood Institute (grants HL065581 and HL065591). The Chicago site

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Doentes com obesidade têm um maior risco de eventos cardiovasculares em prevenção primária. Em prevenção secundária tem sido descrito um paradoxo da obesidade. Foi nosso objetivo estudar uma coorte de indivíduos analisados previamente num estudo transversal sobre a relação entre síndrome metabólica (SM) e doença coronária (DC), estudando presentemente o impacto da SM na ocorrência de eventos cardiovasculares a longo‐prazo.
Foram analisados 296 indivíduos num seguimento médio de 6,9 ± 2,2 anos. Os indivíduos foram divididos em quatro grupos em função da presença ou ausência de SM e de DC (estenoses coronárias ≥ 70%).
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The MHO prevalence was 4.8% (n = 146) with 28.2% of obese participants presenting metabolically healthy status at baseline. Within this group, 52% developed unhealthy metabolic status during the 10-year follow up. MHO vs. metabolically healthy non-obese participants had a higher likelihood of presenting with 10-year CVD events, yet only the subset of them who lost their baseline status reached the level of significance (Hazard Ratio (HR) = 1.43, 95% Confidence Interval (95% CI) 1.02, 2.01). Sensitivity analyses revealed that MHO status was independently associated with elevated CVD risk in women and participants with low adherence to the Mediterranean diet, low grade inflammation, and insulin resistance.
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There are few cross-sectional studies on the MHO CAC association, which have all but one been done in Asian populations with Asian-specific cut-offs to define obesity [11–15]. Khan et al. found in a female mid-life population that the proportion of CAC prevalence was larger in MHO than in MHNW [11]. In two further studies, MHO persons had a larger prevalence of CAC proportion than MHNW persons, but lower CAC prevalence than metabolically unhealthy persons [12,13].
There is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population.
In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. For cross-sectional and longitudinal analyses, we included 1585 participants free of coronary heart disease at baseline, with CAC measurements at baseline and at follow-up, and with either normal weight (BMI 18.5–24.9 kg/m²) or obesity (BMI ≥30.0 kg/m²) at baseline. We used four definitions of MHO. In our main analysis, we defined obese persons as metabolically healthy if they met ≤1 of the NCEP ATP III criteria for the definition of the metabolic syndrome – waist circumference was not taken into account because of collinearity with BMI.
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However, recent long-term studies and meta-analyses have provided robust evidence that MHO is not a benign condition [120,121]. It is associated with subclinical target organ damage, including increased carotid intima-media thickness (IMT) [122], coronary artery calcification [123], subtle impairment of LV structure and function [124] and impaired vasoreactivity [125]. Furthermore, MHO appears to be a transient metabolic state, since these subjects convert to an unhealthy phenotype more frequently and rapidly than their non-obese counterparts (65% conversion rate in 10 years) [126].
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Burden of subclinical cardiovascular disease in “metabolically benign” and “at-risk” overweight and obese women: The Study of Women's Health Across the Nation (SWAN)

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Conflicts of interest

Acknowledgments

American Journal of Cardiology

American Journal of Hypertension

J Am Coll Cardiol

Mayo Clin Proc

Atherosclerosis

The importance of waist circumference in the definition of metabolic syndrome: prospective analyses of mortality in men

Diabetes Care

Metabolically healthy but obese women have an intermediate cardiovascular risk profile between healthy nonobese women and obese insulin-resistant women

Diabetes Care

The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004) [see comment]

Archives of Internal Medicine

Clinical importance of obesity versus the metabolic syndrome in cardiovascular risk in women: a report from the Women's Ischemia Syndrome Evaluation (WISE) study

Circulation

Identification and characterization of metabolically benign obesity in humans [see comment]

Archives of Internal Medicine

Design, survey sampling and recruitment methods of SWAN: a multi-center, multi-ethnic community-based cohort of women and the menopausal transition

Hot flashes and subclinical cardiovascular disease: findings from the Study of Women's Health Across the Nation Heart Study

Circulation