Does HDL-C Classification as a Criterion for Metabolic Syndrome Contribute to Alleviated Risks of Future Atherosclerosis and Incident Diabetes Among Midlife Women? The Study of Women's Health Across the Nation (SWAN)

Introduction: In women, metabolic syndrome (MetS) is identified when at least 3 of the following risk factors exist: waist circumference > 88 cm, HDL-C < 50 mg/dL, triglycerides (TG) ≥ 150 mg/dL, fasting glucose ≥ 110 mg/dL, and hypertension. However, previous studies challenged the belief that HDL-C is protective for midlife women, casting doubts on HDL-C as one of the criteria for diagnosing MetS in this population. Hypothesis: We hypothesize that among midlife women classified as having MetS based on criteria independent of HDL-C, HDL-C classification does not contribute to risk of future subclinical atherosclerosis or incident diabetes. Methods: Participants from the SWAN study with complete data on MetS were classified into the following groups: 1) no MetS or 2) MetS independent of HDL-C; which was classified into MetS with HDL-C ≥ 50 mg/dL (MetS high), or MetS with HDL-C < 50 mg/dL (MetS low). Carotid intima-media thickness (cIMT) was measured after 13.8±0.6 years of follow-up. Incident diabetes was recorded based on medication use, fasting glucose ≥ 126 mg/dL and/or self-reports over time. Linear regression and discrete-time survival analysis were used for analysis. Results: Among 2994 women age 45.9±2.7 years, 2528 had no MetS (88%), 85 had MetS high (3%), and 235 had MetS low (8%) at baseline. In model 1, compared to no MetS group, MetS high or low group had higher cIMT and higher odds of diabetes. The risk did not differ between MetS low vs. high group. Adjusting for levels of MetS criteria other than HDL-C explained the associations of each of the two MetS groups with cIMT. Conversely, MetS with low HDL-C remained associated with a higher risk of incident diabetes ( Table 1 ). Conclusions: Midlife women with MetS have elevated risk for incident diabetes and subclinical atherosclerosis regardless of HDL-C levels. The elevated risk is explained by levels of criteria of MetS other than HDL-C for cIMT but not for diabetes. Low HDL-C on top of other MetS criteria doesn’t contribute equally to future cardiovascular risk prediction in midlife women.