Low Plasma HDL Cholesterol is Associated with Greater Risk for Cardiovascular Disease in Subjects with Metabolic Syndrome

Low plasma HDL cholesterol (HDL-c) has been recognized as a biomarker of cardiovascular disease (CVD) and diabetes. Also, low HDL-c is one of the characteristics of metabolic syndrome (MetS). Objective: To assess whether low HDL-c and/or low HDL functionality are associated with higher risk for CVD in subjects classified with MetS. Methods: Forty-subjects with MetS (11 men /29 women, 52.4 ± 9.5 years participated in the study. Anthropometric data [weight, height, BMI, waist circumference (WC), blood pressure (BP)], fasting plasma biomarkers [lipids, glucose, liver enzymes: alanine aminotransferase (ALT), and aspartate aminotransferase (AST), plasma insulin, and glycosylated hemoglobin (HbA1c)], biomarkers of oxidative stress and inflammation, and biomarkers of antioxidants status [glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and total antioxidant capacity (TAC)] were measured. Lipoproteins particles were measured to identify the size and number. Also, the functionality of HDL was further assessed by measuring plasma apolipoproteins, paraoxonase-1(PON-1) and serum amyloid A1 (SAA1). Results: Participants had a mean BMI of 32.3 ± 2.7 kg/m2 (29.8 – 39.3 kg/m2)placing the majority in the obesity category. In terms of MetS characteristics, all subjects (100%) fit the criteria for WC; 63% either had high systolic BP, high diastolic BP, or both; 70% were hyperglycemic; 48% had elevated plasma triglycerides (TG), and 43% had low HDL-c. We divided the subjects into two categories, Low HDL-c (men \u3c 40 mg/dL and women \u3c 50 mg/dL) (n = 17) and Normal HDL-c (men ≥ 40 mg/dL and women ≥ 50 mg/dL) (n = 23). Those with Low HDL-c had higher systolic BP (129.9 ± 9.7 vs 121.2 ± 14.2 mm Hg, p \u3c 0.05), higher TG (166.6 ± 8.0 vs 115.5 ± 56.8 mg/dl, p \u3c 0.05), and lower TAC (1.23 ± 0.9 vs 2.09 ± 1.5 mM Trolox equivalents, p \u3c 0.05). In addition, strong negative correlations were found between HDL-c concentrations and each of the following parameters: WC (r= - 0.418, p \u3c 0.01), insulin (r=-0.413, p \u3c 0.05) and ALT (r = -0.324, p \u3c 0.05). Lipoprotein data showed that large VLDL, medium VLDL, and small LDL particles were significantly higher in the Low HDL-c group (9.4 ± 6 vs 5.6 ± 4.4 nmol/L, p \u3c 0.05), (25.1 ± 11.3 vs 15.8 ± 8.2 nmol/L, p \u3c 0.01), (822.5 ± 283 vs 522.4 ± 288.2 nmol/L, p \u3c 0.01), respectively. Both large and total HDL particles were higher in the Normal HDL-c group (8.2 ± 4.1 vs 4.3 ± 1.9 µmol/L, p \u3c 0.01), (37.5 ± 4.4 vs 30.8 ± 4.8 µmol/L, p \u3c 0.01), respectively. Apo A-I was significantly higher in Normal HDL-c group (985.4 ± 274.2 vs 790.7 ± 188.1 mg/L, p \u3c 0.05). Also, Apo A-I was positively correlated with total HDL (r = 0.671, p \u3c 0.01) and large HDL particles (r = 0.530, p \u3c 0.01), respectively. PON-1 activity was significantly higher in the Normal HDL-c group (26.7 ± 14.1 vs 12.4 ± 16.1 U/ml, p\u3c 0.05). Conclusion: These data suggest that in these men and women with MetS, measuring both HDL-c concentrations and HDL particles can provide important information about levels and functionality of the protective HDL. In regards to plasma HDL-c, subjects with Low HDL-c appeared to have higher risk for CVD including dyslipidemia, hypertension, and higher concentrations for more atherogenic lipoproteins. Further, TAC, Apo A-I and PON-1 activity were lower among this group. These results confirm that individuals with Low HDL-c and MetS have increased risk for CVD