Implementation of risk enhancers in ASCVD risk estimation and hypolipidemic treatment eligibility: A sex-specific analysis.

OBJECTIVE: Sex-specific data are limited regarding eligibility for hypolipidemic treatment. We aim to explore the sex-specific clinical utility of high-sensitivity C-reactive protein (hsCRP) and carotid ultrasound as risk modifiers for hypolipidemic treatment in primary prevention of atherosclerotic cardiovascular disease (ASCVD). METHODS: We aimed to explore these sex-specific trends in two pooled contemporary independent Greek cohorts (Athens Vascular Registry n = 698, 50.9% women and Menopause Clinic n = 373, 100% women) of individuals without overt ASCVD. Baseline ASCVD risk was estimated using the Systematic COronary Risk Evaluation-2 (SCORE2) tools. The presence of carotid plaque and hsCRP ≥2 mg/L were integrated as risk modifiers. RESULTS: Men had increased odds to achieve target LDL-C levels based on ASCVD risk (23.8% vs. 17.7%, OR: 1.45 95% CI: 1.05-2.00, p = 0.023, for men vs. women). Additionally, considering carotid plaque or high hsCRP levels did not change this association but reduced on-target LDL-C rate in both sexes. Women had decreased odds of being eligible for hypolipidemic treatment by ASCVD risk estimation (11.5% vs. 26.4%, p < 0.001) compared with men. The addition of carotid plaque presence or high hsCRP levels and their combination resulted in a higher relative increase in hypolipidemic treatment eligibility in women (from 11.5% to 70.9% vs. 26.4% to 61.4% for carotid plaque, from 11.5% to 38.5% vs. 26.4% to 50.8% for hsCRP and from 11.5% to 79.1% vs. 26.4% to 75% for their combination, all for women vs. men, pforinteraction < 0.001 for all) than men. CONCLUSIONS: Implementation of carotid plaque and hsCRP levels increases hypolipidemic treatment eligibility more prominently in women than in men. The impact on clinical outcomes in these untreated patients merits further investigation.

Free androgen index as a determinant of arterial stiffness in menopause: a mediation analysis.

OBJECTIVE: Associations of endogenous androgens in menopause with blood pressure (BP) and indices of arterial stiffness are reported, but directional relationships are not clear. Structural equation modeling is a contemporary statistical method, which allows assessment of such relationships and improves pathway understanding. METHODS: We recruited 411 consecutive apparently healthy postmenopausal women who underwent noninvasive vascular evaluation. This included pulse wave analysis (aortic pressures and arterial wave reflections [augmentation index]), measurement of aortic stiffness by pulse wave velocity (PWV), stiffness index (SI), and flow-mediated dilatation. A cumulative marker combining PWV and SI (combined local and aortic arterial stiffness [CAS]) was also assessed. Free androgen index (FAI) was calculated from circulating total testosterone and sex hormone-binding globulin. RESULTS: FAI was an independent determinant of systolic BP (SBP) (P = 0.032), SI (P = 0.042), and PWV (P = 0.027). Under structural equation modeling analysis, FAI was a direct predictor for PWV (beta = 0.149, P = 0.014), SI (beta = 0.154, P = 0.022), and CAS (beta = 0.193, P = 0.02), whereas SBP was a parallel mediator of androgen's vascular effects on PWV (beta = 0.280, P < 0.001) and CAS (beta = 0.248, P = 0.004), but not SI (beta = 0.024, P = 0.404). FAI-induced increase in arterial stiffness via flow-mediated dilatation was not established. FAI was not a determinant of augmentation index. CONCLUSIONS: In healthy postmenopausal women, FAI was directly associated with PWV, SI, and CAS. FAI also directly correlated with SBP, which in turn concurrently increased PWV and CAS. The directional correlations found herein, imply that endogenous androgens may be causally associated with indices of arterial stiffness both directly and indirectly. This hypothesis should be confirmed in further studies with causal design.

Effect of long-term valproate monotherapy on bone mineral density in adults with epilepsy.

BACKGROUND: We evaluated the cross-sectional relationship of duration and dosage of valproate monotherapy on bone mineral density (BMD) in adult patients with epilepsy. METHODS: The BMD at lumbar level (L2-L4) was measured in consecutive adult epileptic patients receiving long-term (> or =2 years) valproate monotherapy by dual energy X-ray absorptiometry (DXA). Blood samples were collected for total serum calcium, phosphorus, magnesium, 25-hydroxyvitamin D(3) and parathormone. Osteopenia and osteoporosis were defined according to the World Health Organization operational BMD definition. Cross-sectional associations were evaluated using Spearman's correlation coefficient. RESULTS: A total of 41 patients were studied (mean age 32.3+/-8.2 years, 12 men, mean duration of valproate monotherapy 10.6+/-7.4 years). Osteopenia was present in 24% of subjects, while no case of osteoporosis was documented. Duration and dosage of valproate monotherapy did not correlate with BMD. No association was documented between duration or dosage of valproate monotherapy and biochemical parameters. CONCLUSIONS: Duration of valproate monotherapy does not correlate with decreased BMD in adult patients with epilepsy. No case of osteoporosis was identified in patients treated with valproate for a mean period of more than ten years. These findings indicate that bone metabolism may not be affected by valproate monotherapy.