HDL-C criterion of the metabolic syndrome and future diabetes and atherosclerosis in midlife women: The SWAN Study.

Objective: High-density lipoprotein cholesterol (HDL-C) is one of 5 components [high blood pressure, glucose, triglycerides, waist circumference, low HDL-C], 3 of which, needed to diagnose metabolic syndrome (MetS). Evolving research shows that higher HDL-C is not necessarily cardioprotective in midlife women, supporting a need to re-evaluate HDL-C's contribution to risks related to MetS. We tested whether risk of future diabetes and higher carotid intima-media thickness (cIMT) differ by HDL-C status in midlife women diagnosed with MetS based on the other 4 components. Methods Midlife women were classified into 3 groups: 1) no MetS, 2) MetS with HDL-C ≥ 50 mg/dL (MetS hiHDL), and 3) MetS with HDL-C < 50 mg/dL (MetS loHDL). cIMT was measured 13.8 ± 0.6 years post baseline. Incident diabetes was assessed yearly. Results: Among 2773 women (1350 (48 %) of them had cIMT), 2383 (86 %) had no MetS, 117 (4 %) had MetS hiHDL, 273 (10 %) had MetS loHDL. Compared with no MetS, both MetS- hiHDL and loHDL groups had higher cIMT and diabetes risk. Risk of having high cIMT did not differ between MetS loHDL vs. hiHDL groups. Adjusting for levels of MetS criteria other than HDL-C at baseline explained the associations of each of the two MetS groups with cIMT. Conversely, after adjustment, associations of MetS hiHDL and MetS loHDL with incident diabetes persisted. Conclusions: In midlife women, HDL-C status matters for predicting risk of incident diabetes but not higher cIMT beyond other MetS components.

High-density lipoprotein metrics during midlife and future subclinical atherosclerosis in women: the SWAN HDL study.

OBJECTIVE: The clinical utility of high-density lipoprotein cholesterol (HDL-C) in risk classification is limited, especially in midlife women. Novel metrics of HDL may better reflect this risk. We clustered a comprehensive profile of HDL metrics into favorable and unfavorable clusters and assessed how these two clusters are related to future subclinical atherosclerosis (carotid intima media thickness [cIMT], interadventitial diameter [IAD], and carotid plaque presence) in midlife women. METHODS: Four hundred sixty-one women (baseline age: 50.4 [2.7] years; 272 White, 137 Black, 52 Chinese) from the Study of Women's Health Across the Nation HDL ancillary study who had baseline measures of HDL cholesterol efflux capacity (HDL-CEC), lipid contents (HDL-phospholipids [HDL-PL] and HDL triglycerides [HDL-Tg]), and HDL particle (HDL-P) distribution and size, followed by carotid ultrasound (average 12.9 [SD: 2.6] years later), were included. Using latent cluster analysis, women were clustered into a favorable (high HDL-CEC, HDL-PL, large and medium HDL-P, less HDL-Tg and small HDL-P, larger size) or an unfavorable HDL cluster (low HDL-CEC, HDL-PL, large and medium HDL-P, more HDL-Tg, and small HDL-P, smaller size) and then linked to future subclinical atherosclerosis using linear or logistic regression. RESULTS: The favorable HDL cluster was associated with lower cIMT, IAD, and odds of carotid plaque presence. These associations were attenuated by body mass index, except in Chinese women where the association with cIMT persisted (0.72 [0.63, 0.83]). CONCLUSIONS: The association between favorable HDL clusters and a better postmenopausal subclinical atherosclerosis profile is largely explained by body mass index; however, racial/ethnic differences may exist.