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)

Abstract
The individual risk of cardiovascular disease (CVD) may depend on both body size and the metabolic profile. Individuals with a similar body mass index (BMI) may express a different clustering of cardiometabolic risk factors (variable body size phenotypes). There are few data regarding the prevalence and correlates of two body size phenotypes, one, a subset of normal-weight individuals displaying cardiometabolic risk factor clustering, and the other a subset of obese individuals resistant to the development of the adiposity-associated cardiometabolic abnormalities. These parameters were examined in an observational study involving 5440 participants of the National Health and Nutrition Examination Surveys (NHANES) 1999–2004 database who were 20 years of age and older. Individuals were classified according to their BMI as either normal weight, <25.0; overweight, 25.0–29.9; and obese, ≥30.0 [calculated as weight in kilograms divided by height in meters squared]. The cardiometabolic abnormalities include elevated blood pressure and insulin resistance; elevated levels of triglycerides, fasting glucose, and C-reactive protein; and reduced level of high density lipoprotein cholesterol (HDL-C). The metabolically healthy phenotype is defined as ≤2 metabolic abnormalities and the metabolically abnormal as ≥3 metabolic abnormalities. Each of 6 body size phenotypes were evaluated: normal-weight, overweight, and obese individuals with or without cardiometabolic abnormalities. A multivariate adjustment regression model was used to calculate the independent risk factors for CVD. The data show that, of the phenotypes expressed as percentage of each BMI group, 51.3% (approximately 35.9 million adults) of overweight adults and 31.7% (approximately 19.5 million adults) of obese adults were metabolically healthy, whereas 23.5% (approximately 16.3 million adults) of normal-weight adults were metabolically abnormal. Among normal-weight individuals, risk factors independently associated with the metabolically abnormal phenotype were older age, larger waist circumference, and lower physical activity. Among overweight and obese individuals, independent risk factors for expression of the metabolically healthy phenotype were younger age, smaller waist circumference, higher physical activity, and non-Hispanic black race/ethnicity. These findings indicate that among US adults there is a high prevalence of overweight and obese individuals who are metabolically healthy, and a high prevalence of normal-weight individuals who express a clustering of cardiometabolic abnormalities.