Abstract

Introduction: Recently, several guidelines suggest the usefulness of non-high density lipoprotein cholesterol (non-HDLC) as a secondary treatment target for CVD prevention, next to low-density lipoprotein cholesterol (LDLC). However, its effect on endothelial dysfunction have not been fully clarified. The objective of this multicenter-prospective-observational study, FMD-J Study, is to evaluate whether non-HDLC is a residual risk for the progression of endothelial dysfunction in patients with hypertension. Hypothesis: Non-HDLC is a residual risk for the progression of endothelial dysfunction in patients with hypertension. Methods: 633 treated hypertensive patients (mean age 62±9 years) in the FMD-J study were followed for 3 years. Endothelial function was evaluated by the change of flow mediated vasodilation (FMD). Multivariate regression analysis adjusted for established coronary heart disease (CHD) risk factors (sex, age, BMI, systolic blood pressure, heart rate, fasting blood glucose, high density lipoprotein cholesterol, baseline FMD, current smoking, treatment of diabetes, and treatment of dyslipidemia) was performed to evaluate whether LDLC and non-HDLC were associated with the change of FMD. We also performed secondary analysis to evaluate whether non-HDLC is associated with progression of endothelial dysfunction in patients with well controlled LDLC level according to their CHD risk. CHD risk was evaluated by Suita score, which is established risk score to assess the 10-year risk of CHD for the Japanese population. (High-risk: 56≦Suita score, Mid-risk: 41≦Suita score≦55, Low-risk: Suita score≦40) Target controlled LDLC levels according to CHD risk were defined as follows; High-risk: LDLC<70 mg/dl, Mid-risk: LDLC<100 mg/dl, Low-risk: LDLC<70 mg/dl. Results: Mean change of FMD after 3 years was 0.07±2.97% and mean Suita score was 46.4±8.9. Overall, both higher LDLC and non-HDLC was significantly associated with impairment of FMD. (Adjusted 1SD increase of LDLC; β: -0.26±0.11, P=0.02, Adjusted 1SD increase of non-HDLC; β: -0.25±0.11, P=0.03 ). In secondary analysis, 97 patients’ LDLC reached target LDLC level according to CHD risk. Among LDLC controlled group, higher non-HDLC was significantly associated with impairment of FMD. (Adjusted 1SD increase of non-HDLC; β: -0.75±0.13, P=0.02). However, among 536 patients whose LDLC did not reach target LDLC value, non-HDLC was not associated with the change pf FMD. (Adjusted 1SD increase of non-HDLC; β: -0.15±0.12, P=0.20). Conclusions: Non-HDLC may be a residual risk for the progression of endothelial dysfunction in patients with hypertension, especially in hypertensive patients with well controlled LDLC.

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