Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Cardiometabolic Risk Factors: A Population-Based Cohort Study

Jie Shi; Xiaoyong Li; Weiwei Zhang; Yixin Niu; Ning Lin; Hongmei Zhang; Guang Ning; Jiangao Fan; Li Qin; Qing Su; Zhen Yang

doi:10.3389/fcvm.2021.664583

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels and Cardiometabolic Risk Factors: A Population-Based Cohort Study

Front Cardiovasc Med. 2021 May 10:8:664583. doi: 10.3389/fcvm.2021.664583. eCollection 2021.

Authors

Jie Shi¹, Xiaoyong Li¹, Weiwei Zhang¹, Yixin Niu¹, Ning Lin¹, Hongmei Zhang¹, Guang Ning², Jiangao Fan³, Li Qin¹, Qing Su¹, Zhen Yang¹

Affiliations

¹ Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Institute of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Key Laboratory of Children's Digestion and Nutrition, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Aims: To evaluate the prospective association of circulating PCSK9 levels with the cardiometabolic risk profiles (high LDL-cholesterol, high triglycerides, low HDL-cholesterol, hypertension, type 2 diabetes, and metabolic syndrome). Methods: A population-based prospective study was conducted among 7,104 Chinese individuals (age 56.2 ± 7.5 years; 32.0% men). Circulating PCSK9 levels were measured using ELISA. Results: Circulating PCSK9 levels were higher in women than men (286.7 ± 90.1 vs. 276.1 ± 86.4 ng/ml, p < 0.001). And circulating PCSK9 was positively correlated with LDL-cholesterol, total cholesterol, and triglycerides both in men and women (all p < 0.001). The positive correlation between PCSK9 and waist circumference, fasting glucose, insulin resistance, systolic blood pressure, diastolic blood pressure and C-reactive protein (all p < 0.01) was observed in women only. According to Cox regression analysis, circulating PCSK9 was positively associated with incidence of high LDL-cholesterol both in men (HR 1.33, 95% CI 1.09-1.65, p < 0.001) and women (HR 1.36, 95% CI 1.12-1.69, p < 0.001). Moreover, PCSK9 was significantly associated with incident high triglycerides (HR 1.31, 95% CI 1.13-1.72, p < 0.001), hypertension (HR 1.28, 95% CI 1.08-1.53, p = 0.011), type 2 diabetes (HR 1.34, 95% CI 1.09-1.76, p = 0.005), and metabolic syndrome (HR 1.30, 95% CI 1.11-1.65, p = 0.009) per SD change in women only. No statistically significant association was observed between circulating PCSK9 and incidence of low HDL-cholesterol (p > 0.1). Conclusions: Elevated circulating PCSK9 was significantly associated with cardiometabolic risk factors and independently contributed to the prediction of cardiometabolic risks in women.

Keywords: cardiometabolic risk factors; dyslipidemia; hypertension; metabolic syndrome; proprotein convertase subtilisin kexin type 9; type 2 diabetes.