Risk Factors Of Subclinical Atherosclerosis And Its Association With Cardiovascular Diseases

BackgroundAs a chronic non-communicable disease with an increasing prevalence,cardiovascular disease(CVD)has become an increasingly prominent global public health problem.With rapid economic development,urbanization and lifestyle changes in recent years,the current situation of CVD in China has become increasingly severe and has become the "number one killer" affecting health and wellness of Chinese adults.Atherosclerosis is the major pathological change throughout the course of CVD.Early detection of subclinical atherosclerosis,identification of risk factors and exploration of effective prevention and treatment methods can prevent the occurrence of clinical cardiovascular events.Objectives1.To examine the status of subclinical atherosclerosis and associated factors in Chinese community residents stratified by normal glucose regulation(NGR),prediabetes and diabetes.2.To investigate the association of coronary plaque types and other subclinical atherosclerosis indicators with CVD risk in Chinese community residents aged ≥40 years.Coronary computed tomography(CT)scanning angiography was used to determine the types of coronary plaque.3.To explore the association between prediabetes,an early stage of glucose disturbance and risks of subclinical atherosclerosis in Chinese community residents aged ≥40 years and to provide evidence for early prevention and control of CVD in Chinese adults.Study Design and MethodsWe used two different study populations from Songnan district and Jiading district in Shanghai,respectively.The prevalence of subclinical atherosclerosis and related factors and the association between coronary plaque types and CVD risks were examined using Songnan population.The association between prediabetes and risks of subclinical atherosclerosis was examined in Jiading population.Songnan population: In 2008,all the permanent residents aged ≥40 years in Songnan community in Shanghai were invited to participate in a survey for cardiovascular and chronic metabolic diseases.Among 10,185 participants,we randomly selected 5,250 subjects using a ratio of 1.0 [diabetes diagnosed previously or fasting plasma glucose(FPG)≥7.0 mmol/L] to 1.2(no previous diabetes and 5.6≤ FPG <7.0 mmol/L)to 1.44(no previous diabetes and FPG <5.6 mmol/L)to undergo a detailed and comprehensive evaluation including a standard 75-g oral glucose tolerance test(OGTT).We then reclassified the participating 4,012 subjects(attendance rate,76.4%)into NGR,prediabetes,and diabetes groups based on their diabetes history and FPG and 2-h postload plasma glucose levels according to the 1999 World Health Organization(WHO)criteria.Questionnaires were used to collect information on medical history and lifestyles,et al.Anthropometric measurements included weight,height,waist circumference and blood pressure.Fasting and 2-hour post-load blood samples were collected to evaluate the glucose and lipid metabolism.The carotid intima-media thickness(CIMT),brachial-ankle pulse wave velocity(ba-PWV),ankle-brachial index(ABI)and urinary albumin-tocreatinine ratio(UACR)were measured in each participant.In addition,942 subjects(including all participants with diabetes or prediabetes,and 50% of participants with NGR)were randomly selected from the 4,012 subjects to undergo coronary CT angiography to evaluate the existence and types of coronary plaques after excluding those with certain conditions.A total of 569 subjects responded.After excluding participants with uninterpretable coronary angiography segments attributable to motion artifacts and participants with missing data on blood pressure,549 participants were eventually included in the current analysis.At least one abnormality in CIMT,ba-PWV,ABI,UACR,or coronary plaques was defined as the presence of overall subclinical atherosclerosis.Jiading population: we recruited 10,375 participants aged ≥40 years using cluster sampling in Jiading District from March to August in 2010 for epidemiological survey including standard questionnaires,anthropometric measurements and biochemical analysis.Carotid plaques,CIMT,ba-PWV,ABI and UACR were measured in each participant.From August 2014 to July 2015,subjects were invited to participate in a follow-up visit.A total of 4,790 subjects completed the questionnaire,physical examination,blood and urine sample collection and measurement of carotid plaque,CIMT,ba-PWV,ABI and UACR during the follow-up visit.Prediabetes was defined by the American Diabetes Association(ADA)criteria and the WHO criteria,respectively.Overall subclinical atherosclerosis was defined by the presence of at least one abnormality in CIMT,ba-PWV,ABI,UACR or carotid plaques.Results1.The prevalence of subclinical atherosclerosis and associated factors(1)The prevalence of subclinical atherosclerosisAmong 549 participants included in the current analysis,the mean age was 52.2±4.2 years,and 42.4% were men.The prevalence of CIMT elevation,ba-PWV acceleration,abnormal ABI,microalbuminuria(UACR ≥30 mg/g),coronary plaques,coronary significant stenosis(≥50%),and overall subclinical atherosclerosis in NGR was 23.4%,20.1%,0.5%,5.7%,45.6%,9.2% and 63.1%,respectively.In prediabetes,the corresponding prevalence was 23.0%,27.0%,0%,3.7%,55.0%,8.4% and 72.1%,respectively.In diabetes,the corresponding prevalence was 26.9%,30.3%,2.5%,11.5%,56.2%,16.9% and 80.0%,respectively.(2)Factors associated with subclinical atherosclerosisIn the logistic regression model,we used elevated CIMT,increased ba-PWV,abnormal ABI,microalbuminuria,coronary plaques,coronary significant stenosis,and overall subclinical atherosclerosis as dependent variables,and age,sex,overweight/obesity,abdominal obesity,hypertension,diabetes,dyslipidemia and metabolic syndrome as independent variables.Results showed that age ≥53 years(odds ratio [OR]=2.00,95% confidence interval [CI] 1.30-3.08),overweight/obesity(OR=1.76,95% CI 1.05-2.94)and hypertension(OR=3.35,95% CI 2.11-5.33)were associated with overall subclinical atherosclerosis.2.Associations of coronary plaques and other subclinical atherosclerosis indicators with CVD risks(1)Associations of coronary plaques with CVD risksAmong 549 participants,267(48.6%)were without coronary plaques,201(36.6%)had non-calcified coronary plaques,and 81(14.8%)had calcified or mixed coronary plaques.Measures of CVD risk including the Framingham risk score(FRS)and the atherosclerotic cardiovascular disease(ASCVD)risk score increased substantially across groups of participants without coronary plaques,with non-calcified coronary plaques,and with calcified or mixed coronary plaques.After adjustment for confounding factors,risks of having elevated FRS increased significantly in participants with non-calcified coronary plaques and calcified or mixed coronary plaques compared with participants without coronary plaques.However,only calcified or mixed coronary plaques were significantly associated with elevated ASCVD risk score(OR=2.41,95% CI 1.09-5.32)compared with participants without coronary plaques,whereas no significant association was found for non-calcified coronary plaques and elevated ASCVD risk score(OR=1.25,95% CI 0.71-2.21)after multivariable adjustments.(2)Associations of other subclinical atherosclerosis indicators with CVD risksOther subclinical atherosclerosis measurements included elevated CIMT,increased ba-PWV,abnormal ABI,and microalbuminuria.The FRS and the ASCVD risk score were significantly increased in subjects with elevated CIMT,increased ba-PWV,microalbuminuria,or overall subclinical atherosclerosis compared with their corresponding normal groups.The associations of increased ba-PWV,microalbuminuria and overall subclinical atherosclerosis with elevated FRS were significant after multivariable adjustment.Moreover,after multivariate adjustment,the associations of increased ba-PWV and overall subclinical atherosclerosis with elevated ASCVD score were also significant.3.Risks of subclinical atherosclerosis in asymptomatic individuals with prediabetes(1)Associations of subclinical atherosclerosis with prediabetes in the cross-sectional analysisAfter adjustment for conventional cardiovascular risk factors,participants with prediabetes diagnosed by individual measures such as FPG and 2-h postload plasma glucose or different criteria(the 1999 WHO criteria,the 2003 ADA criteria,or the 2010 ADA criteria)had an increased risk of increased ba-PWV,microalbuminuria,and overall subclinical atherosclerosis compared with participants with NGR.However,no significant association between prediabetes diagnosed by Hb A1 c and overall subclinical atherosclerosis was found after multivariable adjustment.(2)Associations of subclinical atherosclerosis with prediabetes in the longitudinal analysisPrediabetes was independently associated with risks of increased ba-PWV when defined by FPG,Hb A1 c,or the 2010 ADA criteria after adjustment for conventional cardiovascular risk factors.In addition,prediabetes was independently associated with risks of subclinical atherosclerosis when defined by 2003 ADA criteria after adjustment for conventional cardiovascular risk factors.Conclusions1.The prevalence of elevated CIMT,increased ba-PWV,abnormal ABI,microalbuminuria,coronary plaques,coronary significant stenosis,and overall subclinical atherosclerosis in NGR was 23.4%,20.1%,0.5%,5.7%,45.6%,9.2% and 63.1%,respectively.In prediabetes,the prevalence was 23.0%,27.0%,0%,3.7%,55.0%,8.4% and 72.1%,respectively.In diabetes,the prevalence was 26.9%,30.3%,2.5%,11.5%,56.2%,16.9% and 80.0%,respectively.Age ≥53 years,overweight/obesity and hypertension were significantly associated with the overall subclinical atherosclerosis.2.Calcified or mixed coronary plaques might be more associated with CVD risks than non-calcified coronary plaques.Other subclinical atherosclerosis indicators such as the increased ba-PWV and microalbuminuria were significantly associated with higher CVD risks.3.In the cross-sectional analysis,prediabetes defined by single glycemic measure or different criteria was associated with an increased risk of subclinical atherosclerosis.In addition,prediabetes was associated with an increased risk of increased ba-PWV in the longitudinal analysis.