Association of Circulating Endothelial Microparticles With Cardiometabolic Risk Factors in the Framingham Heart Study

Study Questions:

Are endothelial microparticles (EMPs) associated with increased cardiometabolic risk?

Methods:

The longitudinal cohort of the original Framingham Heart Study (FHS) was used for the present analysis, where 5,124 offspring (and spouses of the offspring) were enrolled in 1971. All FHS Offspring cohort participants receive routine examinations approximately every 4 years. A total of 915 patients who participated in the 2005-2008 examination cycle had fasting blood samples available for characterization of circulation EMP quantity. Of these individuals, 844 participants (mean age 66 years, 57% women) were free of cardiovascular disease, including a history of myocardial infarction, coronary insufficiency, stroke, and heart failure, and were included in the current analysis. Standardized flow cytometry was used to identify and quantify circulating CD144+ and CD31+/CD412 EMPs. Multivariable regression analyses were used to examine the relationship of EMP phenotypes with cardiovascular and metabolic risk factors.

Results:

In age- and sex-adjusted analyses, significant associations for higher CD144+ and CD31+/CD412 EMPs with greater body mass index, larger waist circumference, lower high-density lipoprotein cholesterol, and higher triglycerides were observed. CD144+ was significantly higher in men compared with women, and in the setting of hypertension. In multivariable analyses, the following cardiovascular risk factors were associated with one or more of the circulating EMP populations: hypertension (p = 0.025 for CD144+), elevated triglycerides (p = 0.002 for CD144+, p < 0.0001 for CD31+/CD412), and metabolic syndrome (p < 0.0001 for CD144+). Overall, each tertile increase in the Framingham risk score corresponded to a 9% increase in log CD31+/CD412 EMPs (p = 0.022). Furthermore, the presence of elevated triglycerides (defined as >177 mg/dl) and an increased waist circumference (≥90 cm for men and ≥85 cm for women) was associated with 38% higher levels of CD144+ EMPs (p < 0.0001) and 46% higher levels of CD31+/CD412 EMPs (p < 0.0001).

Conclusions:

The investigators concluded that circulating EMP levels were associated with the presence of cardiometabolic risk factors, particularly dyslipidemia. These data underscore the potential influence of high-risk metabolic profiles on endothelial integrity.

Perspective:

These data may lead to novel markers of cardiovascular risk. Further research is warranted.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Heart Failure and Cardiac Biomarkers, Hypertension

Keywords: Metabolic Syndrome X, Cholesterol, Waist Circumference, Dyslipidemias, Antigens, CD31, Body Mass Index, Risk Factors, Triglycerides, Hypertension


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