Meta-Analysis Of High-Density Lipoprotein Subfractions And The Risk Of Cardiovascular Diseases

Background and ObjectiveAccording to the Global Burden of Disease Study 2016,cardiovascular diseases(CVD),including stroke and coronary heart disease,became the leading cause of disease burden and death in Chinese people.Dyslipidemia is one of the most common controllable risk factors for CVD.According to the 2012 national survey,the prevalence of dyslipidemia in adults reached 40.40%.Current national guidelines for the prevention and treatment of dyslipidemia recommend lowering low-density lipoprotein cholesterol(LDL-C)levels as the primary intervention target.However,several studies found that even with statin treatment to lower LDL cholesterol,patients still had a high residual risk of CVD.A large number of clinical and epidemiological studies confirmed that plasma levels of high-density lipoprotein cholesterol(HDL-C)were negatively correlated with the CVD events.Therefore,the researches on physiological function of HDL-C and the drugs targeted to HDL-C have become a hotspot.However,some studies suggested that plasma HDL-C level may not fully reflect the correlation between HDL and CVD.Drug development aimed at increasing HDL-C blood levels was also deadlocked.Some scholars believe that HDL-C level is not comprehensive and objective in assessing HDL function and predicting CVD risk.They proposed several methods to classify HDL subtypes as alternatives to HDL-C.However,these methods have different evaluations and have not reached a uniform standard.The results of studies on the relationship between HDL subtypes and CVD were different as well.This study conducted a meta-analysis of the included high-quality cohort studies and case-control studies to explore the correlation between HDL subtypes and the CVD risk,so as to provide references for further studies on HDL typing.Materials and methodsThe literatures published on Cochrane Library,Embase,PubMed,China National Knowledge Infrastructure(CNKI),Chinese Biomedical Literature Database(CBM)and Wanfang Database from the establishment of the database to July 2019 related to the relationship between HDL subfractions and cardiovascular diseases were searched.The inclusion and exclusion criteria were strictly followed in the process of literature search.Two researchers independently assessed the quality of the included studies and extracted relevant information.The Stata 12.0 and Review Manager 5.3 software were used for Meta-analysis.I2 statistic was measured to assess heterogeneity.If the heterogeneity was high,sensitivity analyses were conducted to explore potential sources of heterogeneity.Publication bias was evaluated with an Egger test.Results(1)12 studies were involved totally.10 articles using the nuclear magnetic resonance to classify HDL subtypes were involved,including 80,981 participants with a total of 7893 CVD events.3 studies in 2 literatures using ultracentrifugation were involved,including 7,389 participants with a total of 537 cases of coronary heart disease.NOS scores of 13 studies were 6-9.(2)HDL particle(HDLp)[RR=0.84,95%CI(0.80,0.89),P<0.0001]measured by NMR were shown superior correlation with cardiovascular diseases to HDL cholesterol(HDL-C)[RR=0.93,95%CI(0.87,1.00),P=0.05]measured by common methods.Small HDLp(RR=0.89,95%CI(0.84,0.96),P=0.001]in HDLp subtypes may have the strongest negative correlation with cardiovascular and cerebrovascular disease.(3)There was no significant correlation between HDL2 and CVD.HDL3[RR=0.85,95%CI(0.76,0.95),P=0.004,I2=13%]was shown stronger negative correlation with the risk of CVD than HDL-C[RR=0.88,95%CI(0.78,1.00),P=0.04,I2=15%]that measured by current methods.Conclusions(1)HDL-C currently used in clinical cannot reflect the risk of CVD well.(2)The plasma levels of small and dense HDL subtypes defined by ultracentrifugation and NMR were shown inversely relation to CVD events.(3)Plasma levels of HDLp measured by NMR may be inversely related to CVD.