Metabolic Health, BMI, and Long-Term CVD Risk

Study Questions:

Does change in metabolic health over time influence risk of cardiovascular disease (CVD)?


Data from the Nurses’ Health Study (NHS) were used for the present analysis. Female nurses were recruited to the study in 1976. Those who completed a questionnaire in 1980, defined as baseline for the present study, were included. Women were excluded if they had a history of CVD or cancer or were missing data on body weight or were underweight at baseline. Participants were cross-classified by body mass index (BMI) categories, metabolic health (defined by absence of diabetes, hypertension, and hypercholesterolemia), and change in metabolic health status during follow-up. The primary outcome of interest was CVD.


Of the 121,701 nurses enrolled in the NHS, 90,257 who were followed from 1980 to 2010 were included in the present study. During 2,127,391 person-years of follow-up with a median follow-up of 24 years, 6,306 cases of CVD were documented. CVD events included 3,304 myocardial infarction cases and 3,080 strokes. CVD risk of women with metabolically healthy obesity was increased compared to women with metabolically healthy normal weight (hazard ratio, 1.39; 95% confidence interval, 1.15–1.68), but risk was considerably higher in women with metabolically unhealthy normal weight (2.43, 2.19–2.68), overweight (2.61, 2.36–2.89), and obesity (3.15, 2.83–3.50). The majority of metabolically healthy women converted to unhealthy phenotypes (2,555 [84%] of 3,027 women with obesity, 22,215 [68%] of 32,882 women with normal weight after 20 years). Women who maintained metabolically healthy obesity during follow-up were still at a higher CVD risk compared to women with stable healthy normal weight (hazard ratio, 1.57; 95% confidence interval, 1.03–2.38), yet this risk was lower than for initially metabolically healthy women who converted to an unhealthy phenotype (normal weight 1.90, 1.66–2.17 vs. obesity 2.74, 2.30–3.27). In particular, incident diabetes and hypertension increased the risk among women with initial metabolic health.


The authors concluded that CVD risk is highest among women who are metabolically unhealthy across a spectrum of BMI, and that obesity remains a CVD risk factor even when metabolic health is maintained over a long period of time. In addition, a large number of women who were initially metabolically healthy become metabolically unhealthy over time, thus increasing their CVD risk.


These data support the need for effective interventions to prevent weight gain and improve cardiometabolic risk factors as women age.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Hypertension

Keywords: Body Mass Index, Cardiovascular Diseases, Diabetes Mellitus, Hypertension, Metabolic Syndrome X, Myocardial Infarction, Obesity, Overweight, Primary Prevention, Risk Factors, Stroke, Weight Gain, Women

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