The Association Between Serum 25-hydroxyvitamin D And The Risk Of Atherosclerotic Cardiovascular Disease

Objective To explore the association between baseline serum 25-hydroxyvitamin D[25(OH)D] levels and the risk of atherosclerotic cardiovascular disease(ASCVD),especially in patients with type 2 diabetes mellitus.Methods Based on the "REACTION" study conducted in 2011,9014 residents aged 40 to 75 in Lanzhou,Gansu province were followed up from 2014 to 2016.A total of 7061 subjects with complete data from the two surveys in present study were analyzed.According to 25(OH)D quartiles,baseline population was classified into Quartile 1 group(≤11.56ng/ml),Quartile 2 group(11.57-15.91ng/ml),Quartile 3group(15.92-19.98ng/ml)and Quartile 4 group(≥19.99ng/ml),the general clinical characteristics of four groups and the correlation between baseline 25(OH)D level and glycolipid metabolism index were analyzed.Median follow-up 3.3 years after,COX proportional risk regression model was used to analyze the risk factors of ASCVD onset and to estimate associations between 25(OH)D levels and the risk of ASCVD.The research subjects further were divided into normal glucose tolerance(NGT)group,impaired glucose regulation(IGR)group and type 2 diabetes mellitus(T2DM)group according to different glucose metabolism states,the incidence of ASCVD events in different glucose metabolism status and its correlation with baseline25(OH)D level were explored.Results(1)The median serum 25(OH)D level of the total survey population was15.91(11.56,19.98)ng/ml,the prevalence of vitamin D deficiency was 75.1%,which was more common in female than in male(79.6% vs.63.8%)and the rates of vitamin deficiency increased with age,however,merely 2.0% of those with vitamin D sufficiency in middle-aged and elderly population.The baseline serum 25(OH)D concentration was negatively correlated with the levels of FPG,2h-PG,Hb A1 c and TG,the correlation coefficients were-0.041,-0.049,-0.026,-0.029,respectively(all P<0.05),while positively correlated with HDL-C,LDL-C,TC(correlation coefficients were 0.042,0.036,0.027,respectively,all P<0.05).(2)Over a follow-up period of 3.3 years,216 patients experienced ASCVD events,including 69 cases of coronary heart disease and 162 cases of ischemic stroke.Age,hypertension,diabetes,smoking and the levels of WC and Hb A1 c were risk factors for ASCVD,while 25(OH)D was a protective factor(all P<0.05).The cumulative incidence of ASCVD events showed a decreasing trend from the first to the fourth quintile of 25(OH)D(4.1%,3.0%,3.1%,2.0%).With the highest quartile as the reference,the risk of ASCVD increased by 74.8% in subjects with the lowest quartile of 25(OH)D(HR=1.748,95%CI:1.150-2.656,P=0.009).Using serum25(OH)D as a continuous variable,per 10 ng/ml increase in serum 25(OH)D at baseline,ASCVD risk was reduced by 22% after adjusted confounders(HR=0.776,95%CI:0.607-0.992,P=0.043).The protective effect was more pronounced in people with younger than 60 years of age,with diabetes,with hyperlipidemia or central obesity.However,this phenomenon was not observed in patients with coronary heart disease and ischemic stroke.(3)The cumulative incidence of ASCVD events in T2 DM patients was significantly higher than subjects with normal glucose tolerance(NGT)and impaired glucose regulation(IGR)(5.9% vs.1.7%,5.9% vs.2.7%,P<0.001).In T2 DM patients,the ASCVD risk from the first to the fourth quartile of 25(OH)D were 8.8%,5.1%,6.0% and 3.6%,respectively(P for trend was 0.003).In addition,the risk of ASCVD in Q1 group was significantly higher than that in Q4 group(HR=2.359,95%CI:1.275-4.364,P=0.006),and the incidence rate decreased by 36% as serum25(OH)D increased by 10 ng/ml,which remained significant after stepwise adjustments(HR=0.636,95%CI:0.433-0.934,P=0.021).Conclusions(1)Vitamin D levels were closely related to risk factors for ASCVD onset,and baseline serum 25(OH)D concentrations were significantly negatively correlated with FPG,2h-PG,Hb A1 c and TG,while positively correlated with levels of HDL-C,LDL-C and TC.(2)Severe vitamin D deficiency is an independent risk factor for ASCVD,increasing vitamin D levels can effectively reduce the risk of ASCVD incidence,this protective effect is more pronounced in people with younger than 60 years of age,with diabetes,hyperlipidemia or central obesity.(3)The incidence of ASCVD in T2 DM patients is significantly higher than that in normal glucose tolerance population.The extremely low level of vitamin D is an independent risk factor for ASCVD in T2 DM patients,and this correlation was independent of traditional risk factors.