Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults: Synopsis of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline IMProving Adherence using Combination Therapy (IMPACT): design and protocol of a randomised controlled trial in primary care. An analysis of calibration and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort. Cardiovascular complications of HIV: an overview of risk and a novel approach to prevention – the HIV polypill study Association of Nonfasting vs Fasting Lipid Levels With Risk of Major Coronary Events in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm. Polypill for the prevention of cardiovascular disease (PolyIran): study design and rationale for a pragmatic cluster randomized controlled trial Risk score overestimation: the impact of individual cardiovascular risk factors and preventive therapies on the performance of the American Heart Association-American College of Cardiology-Atherosclerotic Cardiovascular Disease risk score in a modern multi-ethnic cohort Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE): rationale and design of a randomised controlled trial of a cardiovascular preventive polypill-based strategy in India and Europe Serum uric acid and risk of death from cancer, cardiovascular disease or all causes in men Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. A polypill strategy to improve adherence: results from the FOCUS project. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. Association of low blood pressure with increased mortality in patients with moderate to severe chronic kidney disease. A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors. The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease. INterpreting the Processes of the UMPIRE Trial (INPUT): protocol for a qualitative process evaluation study of a fixed-dose combination (FDC) strategy to improve adherence to cardiovascular medications A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk Association of fasting glucose levels with incident atherosclerotic cardiovascular disease: An 8‐year follow‐up study in a Chinese population The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)–TIMI 58 Trial Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China)
Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death , decreased quality of life , and medical costs in the United States . Nearly 1 in 3 Americans die of heart disease and stroke ( 1 ) . Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure . The 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association ( ACC/AHA ) provides an evidence -based approach to reducing ASCVD risk ( 2 ) . Guideline Development Process In 2008 , the National Heart , Lung , and Blood Institute ( NHLBI ) convened the Adult Treatment Panel ( ATP ) IV to up date the 2001 ATP-III cholesterol guidelines using a rigorous systematic process to identify and review r and omized , controlled trials ( RCTs ) with cardiovascular outcomes and meta-analyses of these RCTs . The panel comprised experts and clinicians from the fields of cardiology , epidemiology , primary care , and endocrinology ( 2 ) and received support from the Lifestyle Management and Risk Assessment Work Groups ( 3 , 4 ) . Systematic evidence review s conducted according to principles recommended by the Institute of Medicine ( 5 ) were performed to answer 3 questions relevant to clinical care . Two questions focused on the evidence supporting low-density lipoprotein cholesterol ( LDL-C ) and nonhigh-density lipoprotein cholesterol ( HDL-C ) levels as targets of treatment . One question examined the reduction in ASCVD events and adverse effects for each cholesterol-lowering drug class . The panel synthesized the evidence from these 3 review s as well as from Lifestyle Management and Risk Assessment Work Groups review s ( 3 , 4 ) that addressed 5 additional critical questions . Systematic electronic search es of relevant data bases of the peer- review ed English- language literature published from 1 January 1995 through 1 December 2009 for each critical question were conducted by an NHLBI-selected independent contractor and focused on RCTs and systematic review s and meta-analyses of RCTs assessed as fair to good quality . In addition , RCTs with ASCVD outcomes that included coronary heart disease , stroke , and cardiovascular deaths published after that date were eligible for consideration through July 2013 . Evidence tables were constructed , and the strength of evidence was rated according to the NHLBI ( Table 1 of the Supplement ) . Recommendations were grade d according to criteria from the NHLBI ( Table 2 of the Supplement ) and ACC/AHA ( Table 3 of the Supplement ) . Because of the inherent differences in grading systems and the clinical questions driving the recommendations , alignment between the NHLBI and ACC/AHA formats was imperfect . A complete description of the methods used and results of the evidence review are provided in the guideline ( 2 ) and the NHLBI evidence report ( www.nhlbi.nih.gov/ guidelines /cholesterol/ser/index.htm ) . Supplement . NHLBI and ACC/AHA Criteria for Rating Strength of Evidence To help clinicians estimate ASCVD risk , the risk assessment working group developed the Pooled Cohort Equations using data from 5 NHLBI-sponsored longitudinal , population -based cohorts of African American and non-Hispanic white men and women to estimate risk for a first myocardial infa rct ion , coronary heart disease death , or fatal or nonfatal stroke on the basis of age , sex , race , smoking status , total cholesterol level , HDL-C level , systolic blood pressure , antihypertensive therapy , and diabetes ( 4 , 6 ) . These equations significantly advance ASCVD risk estimation by providing sex- and race-specific estimates and including stroke as an outcome . The earlier Framingham equations calculated only coronary heart disease risk for non-Hispanic whites . The draft recommendations were review ed by 23 experts and representatives of federal agencies identified by the NHLBI . In September 2013 , the recommendations developed by the panel were transitioned to the ACC/AHA and had additional review by 4 experts nominated by the ACC Foundation and the AHA . The governing bodies of the ACC and AHA approved the guideline , which also received endorsement from the American Association of Cardiovascular and Pulmonary Rehabilitation , American Pharmacists Association , American Society for Preventive Cardiology , Association of Black Cardiologists , Preventive Cardiovascular Nurses Association , and WomenHeart : The National Coalition for Women with Heart Disease . Recommendations The guideline focuses on treatment of blood cholesterol to reduce ASCVD risk in adults . Major recommendations are summarized here and in Table 1 . The guideline report provides a complete listing of recommendations and supporting evidence behind each recommendation ( 2 ) . Table 1 . Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults * 1 . Encourage Adherence to a Healthy Lifestyle A healthy lifestyle is the foundation for cardiovascular health . The panel endorsed the 2013 ACC/AHA Lifestyle Management Guideline ( 3 ) for a diet that is low in saturated fat , trans fat , and sodium ; emphasizes vegetables , fruits , whole grains , low-fat dairy products , poultry , fish , legumes , nontropical vegetable oils , and nuts ; and limits sweets , sugar-sweetened beverages , and red meats and engage in regular aerobic physical activity . Adults also should maintain a healthy body weight , avoid smoking , and control hypertension and diabetes when present . 2 . Statin Therapy Is Recommended for Adults in Groups Demonstrated to Benefit Strong RCT evidence shows that reduction in ASCVD events from statin therapy exceeds adverse events for 4 patient groups : those with clinical ASCVD ( acute coronary syndromes , myocardial infa rct ion , stable angina , coronary or other arterial revascularization , stroke , transient ischemic attack , or peripheral arterial disease of atherosclerotic origin ) when  statins are used for secondary prevention , and those with LDL-C levels 190 mg/dL ; those aged 40 to 75 years with diabetes and LDL-C levels 70 to 189 mg/dL ; and those aged 40 to 75 years without diabetes and with a 10-year ASCVD risk 7.5 % when statins are used for primary prevention . Moderate evidence supports consideration of statin therapy for primary prevention in individuals with a 10-year ASCVD risk of 5 % to < 7.5 % . Routine initiation of statin therapy is not recommended in adults with New York Heart Association heart failure class II to IV or those receiving maintenance hemodialysis . R and omized , controlled trials in these groups showed no reduction in ASCVD . 3 . Statins have an Acceptable Margin of Safety When Used in Properly Selected Individuals and Appropriately Monitored Strong RCT evidence supports safety of statins when they are used as directed in conjunction with regular follow-up assessment s in properly selected patients . Adjustment of statin intensity is recommended in individuals older than 75 years with a history of statin intolerance or other characteristics ( 2 ) or those receiving drug therapy that may increase statin adverse events . Routine monitoring of hepatic aminotransferase level or creatine kinase level is not recommended unless clinical ly indicated by symptoms suggesting hepatotoxicity or myopathy . Given the potential for decreasing ASCVD events and death , the relationship of muscle and other symptoms to statin treatment must be confirmed . Therefore , eliciting a history of muscle symptoms before statin initiation and carefully monitoring symptoms during statin discontinuation and rechallenge is recommended . Severe myopathy , rhabdomyolysis , and possibly hemorrhagic stroke are rare complications of statin therapy . Although statin therapy modestly increases the risk for type 2 diabetes , ASCVD risk reduction outweighs the excess risk for diabetes for high-intensity statins in secondary prevention or for 10-year ASCVD risk 7.5 % . Similarly , ASCVD risk reduction outweighs the excess risk for diabetes for moderate-intensity statin therapy in adults with a 10-year ASCVD risk 5 % . 4 . Engage in a ClinicianPatient Discussion Before Initiating Statin Therapy , Especially for Primary Prevention in Patients With Lower ASCVD Risk Decisions to initiate statin therapy in primary prevention should be based on clinical judgment and preferences of informed patients . In adults without clinical ASCVD or diabetes whose LDL-C level is < 190 mg/dL , calculating the estimated 10-year ASCVD risk should be the start of the clinicianpatient discussion and should not automatically lead to statin initiation . As the absolute risk for ASCVD events decreases , so does the net benefit of the intervention . Therefore , discussion of the potential for ASCVD event reduction , adverse effects , drugdrug interactions , and patient preferences is especially important for lower-risk primary prevention . The discussion provides the opportunity to encourage healthy lifestyle habits and control other risk factors . Additional factors may be considered when a risk-based decision is uncertain , including LDL-C levels 160 mg/dL , family history of premature ASCVD , elevated  lifetime ASCVD risk  , high-sensitivity C-reactive protein level 2.0 mg/L ,  coronary artery calcification score  > 300 Agatston units , and anklebrachial index < 0.9 . After age 75 years , comorbid conditions , anticipated longevity , safety considerations , and patient preferences should play a large role in decision making . 5 . Use the Newly Developed Pooled Cohort Equations for Estimating 10-Year ASCVD Risk The Pooled Cohort Equations are currently the best available method for estimating 10-year ASCVD risk to guide statin initiation ( 4 , 6 ) . Application of the inclusion and exclusion criteria from RCTs is cumbersome and results in underidentifying high-risk and overidentifying low-risk individuals for statin treatment . The Pooled Cohort Equations were developed using recent data from 5 NHLBI-sponsored , longitudinal , population -based cohorts of African American and white men and women ( ARIC [ BACKGROUND Cardiovascular disease ( CVD ) is the leading cause of death , and principal reason for the large difference in life expectancy between indigenous Māori and the non-indigenous population in New Zeal and . CVD guidelines recommend that people who are at high risk or who have had previous CVD should be offered aspirin , blood pressure lowering and lipid lowering therapies . However , prescribing and adherence rates are low and CVD events remain high . AIM To assess whether a medication strategy using a fixed dose combination pill ( ' polypill ' ) could improve prescribing and adherence to recommended medications , lower blood pressure and improve lipids compared with current care over 12 months . METHODS IMProving Adherence using Combination Therapy ( IMPACT ) is an open-label r and omised controlled trial comparing a once-daily polypill containing four preventive medications with usual care .  Six hundred participants who have had previous CVD events or are at high risk of CVD will be enrolled , including 300 Māori . Participants are identified , enrolled and prescribed either the polypill or current medications at their usual primary health care practice , with medications ( including the polypill ) dispensed through local community pharmacies . The polypill contains 75 mg aspirin , 40 mg simvastatin , 10 mg lisinopril and either 12.5 mg hydrochlorothiazide or 50 mg atenolol . Primary outcomes are adherence to guidelines -recommended medications and changes in systolic blood pressure and low density lipoprotein at 12 months . Secondary outcomes include other lipids , medication dispensing , barriers to adherence , CVD and other serious adverse events , quality of life and prescriber acceptability . The trial is registered with the Australian New Zeal and Clinical Trial Registry ( ACTRN12606000067572 ) BACKGROUND Accurate risk assessment of atherosclerotic cardiovascular disease ( ASCVD ) is essential to effectively balance the risks and benefits of therapy for primary prevention . OBJECTIVE To compare the calibration and discrimination of the new American Heart Association ( AHA ) and American College of Cardiology ( ACC ) ASCVD risk score with alternative risk scores and to explore preventive therapy as a cause of the reported risk overestimation using the AHA-ACC-ASCVD score . DESIGN Prospect i ve epidemiologic study of ASCVD . SETTING MESA ( Multi-Ethnic Study of Atherosclerosis ) , a community-based , sex-balanced , multiethnic cohort . PATIENTS 4227 MESA participants aged 50 to 74 years and without diabetes at baseline . MEASUREMENTS Observed and expected events for the AHA-ACC-ASCVD score were compared with 4 commonly used risk scores- and their respective end points-in MESA after a 10.2-year follow-up . RESULTS The new AHA-ACC-ASCVD and 3 older Framingham-based risk scores overestimated cardiovascular events by 37 % to 154 % in men and 8 % to 67 % in women . Overestimation was noted throughout the continuum of risk . In contrast , the Reynolds Risk Score overestimated risk by 9 % in men but underestimated risk by 21 % in women .  Aspirin , lipid-lowering or antihypertensive therapy  , and  interim revascularization  did not explain the overestimation . LIMITATION Comparability of MESA with target population s for primary prevention and possibility of missed events in MESA . CONCLUSION Of the 5 risk scores , 4 , including the new AHA-ACC-ASCVD score , showed overestimation of risk ( 25 % to 115 % ) in a modern , multiethnic cohort without baseline clinical ASCVD . If vali date d , overestimation of ASCVD risk may have substantial implication s for individual patients and the health care system . PRIMARY FUNDING SOURCE National Heart , Lung , and Blood Institute Purpose of review To review the risk of cardiovascular complications in HIV-infected patients receiving combination antiretroviral treatment .  Recent findings Recent data suggest that patients with chronic HIV infection will require continuous lifelong combination antiretroviral treatment , which may increase the risk of cardiovascular disease in all population s by substantial amounts . Simple , safe and effective interventions to reduce cardiovascular complications in HIV-infected patients will be required . Studies in the general population suggest that the primary prevention of cardiovascular disease with a pill combining blood-pressure-lowering , cholesterol-lowering and antiplatelet treatments ( a polypill ) might decrease cardiovascular events . An HIV polypill study with 8000 HIV-infected patients with a moderate risk of cardiovascular disease r and omized to either a polypill of low-dose pravastatin , aspirin , hydrochlorothiazide and lisinopril or to placebo is described . The primary clinical endpoint would be a composite of cardiovascular mortality , non-fatal myocardial infa rct ion and stroke .  A vanguard study of 400 patients could assess changes in cholesterol , blood pressure and other risk factors . The clinical endpoint study described would have 80 % power to detect a 23 % reduction in the rate of cardiovascular events in the polypill arm . Summary A study of a polypill like that proposed for the general population will provide crucial information on the risks and benefits of primary cardiovascular prevention in HIV-infected patients Importance Recent guidelines have recommended nonfasting for routine testing of lipid levels based on comparisons of nonfasting and fasting population s. However , no previous study has examined the association of cardiovascular outcomes with fasting vs nonfasting lipid levels measured in the same individuals . Objective To compare the association of nonfasting and fasting lipid levels with prospect ively ascertained coronary and vascular outcomes and to evaluate whether a strategy of using nonfasting instead of fasting lipid level measurement would result in misclassification of risk for individuals undergoing evaluation for initiation of statin therapy . Design , Setting , and Participants This post hoc prospect i ve follow-up of a r and omized clinical trial included 8270 of 10 305 participants from the Anglo-Sc and inavian Cardiac Outcomes Trial-Lipid Lowering Arm ( ASCOT-LLA ) with nonfasting and fasting lipid levels measured 4 weeks apart ( including 6855 participants with no prior vascular disease ) ( median follow-up , 3.3 years ; interquartile range , 2.8 - 3.6 years ) . Data were collected from February 1 , 1998 , to December 31 , 2002 , and analyzed from February 1 , 2016 , to November 30 , 2018 . Multivariable Cox models , adjusted for cardiovascular risk factors , were calculated for 40-mg/dL ( 1-mmol/L ) higher values of nonfasting and fasting lipids . Main Outcomes and Measures The trial 's primary end point consisted of major coronary events ( nonfatal myocardial infa rct ion [ MI ] and fatal coronary heart disease [ 212 events ] ) . Secondary analyses examined atherosclerotic cardiovascular disease ( ASCVD ) events ( including MI , stroke , and ASCVD death [ 351 events ] ) . Results Among the 8270 participants ( 82.1 % male ; mean [ SD ] age , 63.4 [ 8.5 ] years ) , nonfasting sample s had modestly higher triglyceride levels and similar cholesterol levels compared to fasting sample s. Associations of  nonfasting lipid levels with coronary events were similar to those for fasting lipid levels . For example , adjusted hazard ratios ( HRs ) per 40-mg/dL of low-density lipoprotein cholesterol were 1.32 ( 95 % CI , 1.08 - 1.61 ; P = .007 ) for nonfasting levels and 1.28 ( 95 % CI , 1.07 - 1.55 ; P = .008 ) for fasting levels . For the primary prevention group , adjusted HRs were 1.42 ( 95 % CI , 1.13 - 1.78 ; P = .003 ) for nonfasting levels and 1.37 ( 95 % CI , 1.11 - 1.69 ; P = .003 ) for fasting levels . Results were consistent by r and omized treatment arm ( atorvastatin calcium , 10 mg/d , or placebo ) and similar for ASCVD events . Concordance of fasting and nonfasting lipid levels for classifying participants into appropriate ASCVD risk categories was high ( 94.8 % ) . Conclusions and Relevance Measurement of nonfasting and fasting lipid levels yields similar results in the same individuals for association with incident coronary and ASCVD events . These results suggest that routine measurement of nonfasting lipid levels may help facilitate ASCVD risk screening and treatment , including consideration of when to initiate statin therapy Background The complexity of treatment regimens , costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage . The polypill , a fixed dose combination pill of established drugs , is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events ( MCVE ) . Design and methods The PolyIran trial is a pragmatic cluster r and omized trial nested within the Golestan Cohort Study ( GCS ) . Subjects were r and omized to either non-pharmacological preventive interventions alone ( minimal care arm ) or together with a polypill ( polypill arm ) comprising hydrochlorothiazide , aspirin , atorvastatin and either enalapril or valsartan . This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers ( Behvarz ) to the participants . The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infa rct ion , unstable angina , sudden death , heart failure , coronary artery revascularization procedures , and non-fatal and fatal stroke . Trial status From February 2011 to April 2013 , 8410 individuals ( 236 clusters ) attended the eligibility assessment . Of those , 3421 in the polypill arm and 3417 in the minimal care arm were eligible . The study is ongoing . Conclusion The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial . If the polypill strategy proves effective , it may be implemented to prevent cardiovascular disease in developing countries Aims To evaluate the 2013 American Heart Association (AHA)-American College of Cardiology (ACC)-Atherosclerotic Cardiovascular Disease ( ASCVD ) risk score among four different race/ethnic groups and to ascertain which factors are most associated with risk overestimation by the AHA-ACC-ASCVD score . Methods and results The Multi-Ethnic Study of Atherosclerosis ( MESA ) , a prospect i ve community-based cohort , was used to examine calibration and discrimination of the AHA-ACC-ASCVD risk score in 6441 White , Black , Chinese , and Hispanic Americans ( aged 45 - 79 years and free of known ASCVD at baseline ) . Using univariable and multivariable absolute risk regression , we modelled the impact of individual risk factors on the discordance between observed and predicted 10-year ASCVD risk . Overestimation was observed in all race/ethnic groups in MESA and was highest among Chinese ( 252 % for women and 314 % for men ) and lowest in White women ( 72 % ) and Hispanic men ( 67 % ) . Higher age , Chinese race/ethnicity ( when compared with White ) , systolic blood pressure ( treated and untreated ) , diabetes , alcohol use , exercise , lipid-lowering medication , and aspirin use were all associated with more risk overestimation , whereas family history was associated with less risk overestimation in a multivariable model ( all P < 0.05 ) . Conclusion The AHA-ACC-ASCVD risk score overestimates ASCVD risk among men , women , and all four race/ethnic groups evaluated in a modern American primary prevention cohort . Clinicians treating patients similar to those in MESA , particularly older individuals and those with factors associated with more risk overestimation , may consider interpreting absolute ASCVD risk estimates with caution The use of preventive medications in people at high risk of cardiovascular disease is conceptually straightforward , yet in practice the adoption of such measures is disappointingly low , plus there is wide international variation in preventive therapies . Several barriers might explain this shortfall and variation , but the simplicity and economy of a polypill-based strategy might overcome some barriers . The ‘ Use of a Multidrug Pill In Reducing cardiovascular Events ’ ( UMPIRE ) trial assesses whether a polypill strategy ( by combining aspirin , a statin and two blood pressure lowering agents ) would improve adherence to guideline -indicated therapies and would lower both blood pressure and cholesterol , in people with established cardiovascular disease . UMPIRE , running in India and three European countries ( Engl and , Irel and and the Netherl and s ) , is an open , r and omised , controlled trial design ed to include 1000 participants in India and 1000 in Europe , with a followup of 12–24 months . Participants were r and omised to one of two versions of the polypill or relegated to usual care . The primary study outcomes were the self-reported use of aspirin , a statin and at least two blood pressure lowering agents ; as well as changes in blood pressure and cholesterol . Secondary outcomes included : any cardiovascular events , reasons for stopping medications , serious adverse events and perceived changes in quality of life . Interpretation of the study data will be enhanced by health , economic and process-related evaluations . UMPIRE is registered with the European Clinical Trials data base , as EudraCT : 2009 - 016278 - 34 and the Clinical Trials Registry , India as CTRI/2010/091/000250 . The trial was part of the ‘ Single Pill Against Cardiovascular Events ( SPACE ) ’ collaboration , which encompasses the ‘ IMProving Adherence using Combination Therapy ( IMPACT ) ’ and ‘ Kanyini Guidelines Adherence with the Polypill ( Kanyini-GAP ) ’ trials Objective Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for mortality , this relationship remains uncertain . This cohort study examined the effects of serum uric acid level on death from cancer , atherosclerotic cardiovascular disease ( ASCVD ) or all causes in men . Method A 9-year , prospect i ve cohort study was carried out with 22 698 Korean men , aged 30 to 77 years , who received health insurance from the National Health Insurance Corporation and who underwent biennial , secondary medical evaluations in 1992–1996 . The main outcome measures were death from cancer , ASCVD or all causes , compared by quintiles of serum uric acid level . At baseline , the mean ( SD ) level of serum uric acid was 354.4 ( 98.1 ) μmol/l . Results During 199 746 person-years of follow-up , there were 387 cancer deaths , 323 ASCVD ( 99 ischaemic heart disease , 192 stroke ) deaths and 1625 all-cause deaths . In multivariate Cox proportional hazards models , having controlled for age , current smoking , diabetes , hypertension and hypercholesterolaemia , uric acid levels were not associated with mortality from cancer , ASCVD or all causes . However , for those with diabetes , uric acid levels were associated with mortality from all causes even after full adjustment of the covariates . When the interaction term was included in the multivariate model , there was significant interactive effect of uric acid with diabetes ( RR = 1.26 , 95 % confidence interval 1.02–1.55 ) on the risk of all cause of death , whereas the effects of uric acid itself did not attain significance . Conclusion These findings indicate that uric acid level is not an independent risk factor for death from cancer , ASCVD or all causes OBJECTIVES The purpose of this study was to determine the prognostic accuracy of electron beam computed tomographic ( CT ) scanning of the coronary arteries and the relationship of coronary calcification to st and ard coronary disease risk factors and C-reactive protein ( CRP ) in the prediction of atherosclerotic cardiovascular disease ( ASCVD ) events in apparently healthy middle-age persons . BACKGROUND As a screening test for coronary artery disease ( CAD ) , electron beam CT scanning remains controversial . METHODS In a prospect i ve , population -based study , 4,903 asymptomatic persons age 50 to 70 years underwent  electron beam CT scanning of the coronary arteries . RESULTS At 4.3 years , follow-up was available in 4,613 participants ( 94 % ) , and 119 had sustained at least one ASCVD event . Subjects with ASCVD events had higher baseline coronary calcium scores ( median [ interquartile range ] , Agatston method ) than those without events : 384 ( 127 , 800 ) versus 10 ( 0 , 86 ) ( p < 0.0001 ) . For coronary calcium score threshold > or = 100 versus < 100 , relative risk ( 95 % confidence interval ) was 9.6 ( 6.7 to 13.9 ) for all ASCVD events , 11.1 ( 7.3 to 16.7 ) for all CAD events , and 9.2 ( 4.9 to 17.3 ) for non-fatal myocardial infa rct ion and death . The coronary calcium score predicted CAD events independently of st and ard risk factors and CRP ( p = 0.004 ) , was superior to the Framingham risk index in the prediction of events ( area under the receiver-operating characteristic curve of 0.79 + /- 0.03 vs. 0.69 + /- 0.03 , p = 0.0006 ) , and enhanced stratification of those falling into the Framingham categories of low , intermediate , and high risk ( p < 0.0001 ) . CONCLUSIONS The electron beam CT coronary calcium score predicts CAD events independent of st and ard risk factors , more accurately than st and ard risk factors and CRP , and refines Framingham risk stratification BACKGROUND Adherence to evidence -based cardiovascular ( CV ) medications after an acute myocardial infa rct ion ( MI ) is low after the first 6 months . The use of fixed-dose combinations ( FDC ) has been shown to improve treatment adherence and risk factor control . However , no previous r and omized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients . OBJECTIVES The cross-sectional FOCUS ( Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention ) study ( Phase 1 ) aim ed to eluci date factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI . Additionally , 695 patients from Phase 1 were r and omized into a controlled trial ( Phase 2 ) to test the effect of a polypill ( containing aspirin 100 mg , simvastatin 40 mg , and ramipril 2.5 , 5 , or 10 mg ) compared with the 3 drugs given separately on adherence , blood pressure , and low-density lipoprotein cholesterol , as well as safety and tolerability over a period of 9 months of follow-up . METHODS In Phase 1 , a 5-country cohort of 2,118 patients was analyzed . Patients were r and omized to either the polypill or 3 drugs separately for Phase 2 . Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green question naire ( MAQ ) and pill count ( patients had to meet both criteria for adherence at the in-person visit to be considered adherent ) . RESULTS In Phase 1 , overall CV medication adherence , defined as an MAQ score of 20 , was 45.5 % . In a multivariable regression model , the risk of being nonadherent ( MAQ < 20 ) was associated with younger age , depression , being on a complex medication regimen , poorer health insurance coverage , and a lower level of social support , with consistent findings across countries . In Phase 2 , the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up : 50.8 % versus 41 % ( p = 0.019 ; intention-to-treat population ) and 65.7 % versus 55.7 % ( p = 0.012 ; per protocol population ) when using the primary endpoint , attending the final visit with MAQ = 20 and high pill count ( 80 % to 110 % ) combined , to assess adherence . Adherence also was higher in the FDC group when measured by MAQ alone ( 68 % vs. 59 % , p = 0.049 ) . No treatment difference was found at follow-up in mean systolic blood pressure ( 129.6 mm Hg vs. 128.6 mm Hg ) , mean low-density lipoprotein cholesterol levels ( 89.9 mg/dl vs. 91.7 mg/dl ) , serious adverse events ( 23 vs. 21 ) , or death ( 1 , 0.3 % in each group ) . CONCLUSIONS For secondary prevention following acute MI , younger age , depression , and a complex drug treatment plan are associated with lower medication adherence . Meanwhile , adherence is increased in patients with higher insurance coverage levels and social support . Compared with the 3 drugs given separately , the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI . ( Fixed Dose Combination Drug [ Polypill ] for Secondary Cardiovascular Prevention [ FOCUS ] ; NCT01321255 ) In 2016 , the American College of Cardiology published the first expert consensus decision pathway ( ECDP ) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease ( ASCVD ) risk . Since the publication of that document , additional evidence and perspectives have emerged from r and omized clinical trials and other sources , particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 ( PCSK9 ) inhibitors in secondary prevention of ASCVD . Most notably , the FOURIER ( Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk ) trial and SPIRE-1 and -2 ( Studies of PCSK9 Inhibition and the Reduction of Vascular Events ) , assessing evolocumab and bococizumab , respectively , have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients . In addition , further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published . Based on results from these important analyses , the ECDP writing committee judged that it would be desirable to provide a focused up date to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities . In the following summary table , changes from the 2016 ECDP to the 2017 ECDP Focused Up date are highlighted , and a brief rationale is provided . The content of the full document has been changed accordingly , with more extensive and detailed guidance regarding decision making provided both in the text and in the up date d algorithms . Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities  on statin therapy for secondary prevention . The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C < 190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes . Based on feedback and further deliberation , the ECDP writing committee down- grade d recommendations regarding bile acid sequestrant use , recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe . For clarification , the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia , based on clinical criteria with and without genetic testing . Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians , unless there was a compelling reason or new evidence , in which case justification is provided Objective To evaluate whether provision of fixed dose combination treatment improves adherence and risk factor control compared with usual care of patients at high risk of cardiovascular disease in primary care . Design Open label r and omised control trial : IMPACT ( IMProving Adherence using Combination Therapy ) . Setting 54 general practice s in the Auckl and and Waikato regions of New Zeal and , July 2010 to August 2013 . Participants 513 adults ( including 257 indigenous Māori ) at high risk of cardiovascular disease ( established cardiovascular disease or five year risk ≥15 % ) who were recommended for treatment with antiplatelet , statin , and two or more blood pressure lowering drugs . 497 ( 97 % ) completed 12 months ’ follow-up . Interventions Participants were r and omised to continued usual care or to fixed dose combination treatment ( with two versions available : aspirin 75 mg , simvastatin 40 mg , and lisinopril 10 mg with either atenolol 50 mg or hydrochlorothiazide 12.5 mg ) . All drugs in both treatment arms were prescribed by their usual general practitioners and dispensed by local community pharmacists . Main outcome measures Primary outcomes were self reported adherence to recommended drugs ( antiplatelet , statin , and two or more blood pressure lowering agents ) and mean change in blood pressure and low density lipoprotein cholesterol at 12 months . Results Adherence to all four recommended drugs was greater among fixed dose combination than usual care participants at 12 months ( 81 % v 46 % ; relative risk 1.75 , 95 % confidence interval 1.52 to 2.03 , P<0.001 ; number needed to treat 2.9 , 95 % confidence interval 2.3 to 3.7 ) . Adherence for each drug type at 12 months was high in both groups but especially in the fixed dose combination group : for antiplatelet treatment it was 93 % fixed dose combination v 83 % usual care ( P<0.001 ) , for statin 94 % v 89 % ( P=0.06 ) , for combination blood pressure lowering 89 % v 59 % ( P<0.001 ) , and for any blood pressure lowering 96 % v 91 % ( P=0.02 ) . Self reported adherence was highly concordant with dispensing data ( dispensing of all four recommended drugs 79 % fixed dose combination v 47 % usual care , relative risk 1.67 , 95 % confidence interval 1.44 to 1.93 , P<0.001 ) . There was no statistically significant improvement in risk factor control between the fixed dose combination and usual care groups over 12 months : the difference in systolic blood pressure was −2.2 mm Hg ( −4.5 v −2.3 , 95 % confidence interval −5.6 to 1.2 , P=0.21 ) , in diastolic blood pressure −1.2 mm Hg ( −2.1 v −0.9 , −3.2 to 0.8 , P=0.22 ) and in low density lipoprotein cholesterol −0.05 mmol/L ( −0.20 v −0.15 , −0.17 to 0.08 , P=0.46 ) . The number of participants with cardiovascular events or serious adverse events was similar in both treatment groups ( fixed dose combination 16 v usual care 18 ( P=0.73 ) , 99 v 93 ( P=0.56 ) , respectively ) . Fixed dose combination treatment was discontinued in 94 participants ( 37 % ) . The most commonly reported reason for discontinuation was a side effect ( 54/75 , 72 % ) . Overall , 89 % ( 227/256 ) of fixed dose combination participants ’ general practitioners completed a post-trial survey , and the fixed dose combination strategy was rated as satisfactory or very satisfactory for starting treatment ( 206/227 , 91 % ) , blood pressure control ( 180/220 , 82 % ) , cholesterol control ( 170/218 , 78 % ) , tolerability ( 181/223 , 81 % ) , and prescribing according to local guidelines ( 185/219 , 84 % ) . When participants were asked at 12 months how easy they found taking their prescribed drugs , most responded very easy or easy ( 224/246 , 91 % fixed dose combination v 212/246 , 86 % usual care , P=0.09 ) . At 12 months the change in other lipid fractions , difference in EuroQol-5D , and difference in barriers to adherence did not differ significantly between the treatment groups . Conclusions Among this well treated primary care  population  , fixed dose combination treatment improved adherence to the combination of all recommended drugs but improvements in clinical risk factors were small and did not reach statistical significance . Acceptability was high for both general practitioners and patients , although the discontinuation rate was high . Trial registration Australian New Zeal and Clinical Trial Registry ACTRN12606000067572 OBJECTIVES We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease ( ASCVD ) events . BACKGROUND The electron beam computed tomography-derived coronary calcium score predicts coronary disease events . Small , uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events , but controlled , scientific demonstration of these effects is lacking . METHODS We conducted a double-blind , placebo-controlled r and omized clinical trial of atorvastatin 20 mg daily , vitamin C 1 g daily , and vitamin E ( alpha-tocopherol ) 1,000 U daily , versus matching placebos in 1,005 asymptomatic , apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender . All study participants also received aspirin 81 mg daily . Mean duration of treatment was 4.3 years . RESULTS Treatment reduced total cholesterol by 26.5 % to 30.4 % ( p < 0.0001 ) , low-density lipoprotein cholesterol by 39.1 % to 43.4 % ( p < 0.0001 ) , and triglycerides by 11.2 % to 17.0 % ( p < or = 0.02 ) but had no effect ( p = 0.80 ) on progression of coronary calcium score ( Agatston method ) . Treatment also failed to significantly reduce the primary end point , a composite of all ASCVD events ( 6.9 % vs. 9.9 % , p = 0.08 ) . Event rates were related to baseline calcium score ( pre-specified analysis ) and may have been reduced in a subgroup of participants with baseline calcium score > 400 ( 8.7 % vs. 15.0 % , p = 0.046 [ not a pre-specified analysis ] ) . CONCLUSIONS Treatment with alpha-tocopherol , vitamin C , and low doses of atorvastatin ( 20 mg once daily ) did not affect the progression of coronary calcification . Treatment may have reduced ASCVD events , especially in subjects with calcium scores > 400 , but these effects did not achieve conventional levels of statistical significance OBJECTIVES The goal of this study was to determine whether the level of kidney function  is an independent risk factor for atherosclerotic cardiovascular disease ( ASCVD ) outcomes in the Atherosclerosis Risk in Communities ( ARIC ) study , a prospect i ve cohort study of subjects aged 45 to 64 years . BACKGROUND The level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD , but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community . METHODS Cox proportional-hazards regression was used to evaluate the association of glomerular filtration rate ( GFR ) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects . We search ed for nonlinear relationships between GFR and ASCVD . RESULTS During a mean follow-up time of 6.2 years , 965 ( 6.3 % ) of subjects had ASCVD events . Subjects with GFR of 15 to 59 ml/min/1.73 m(2 ) ( n = 444 , hazard ratio 1.38 [ 1.02 , 1.87 ] ) and 60 to 89 ml/min/1.73 m(2 ) ( n = 7,665 , hazard ratio 1.16 [ 1.00 , 1.34 ] ) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m(2 ) . Each 10 ml/min/1.73 m(2 ) lower GFR was associated with an adjusted hazard ratio of 1.05 ( 1.02 , 1.09 ) , 1.07 ( 1.01 , 1.12 ) , and 1.06 ( 0.99 , 1.13 ) for ASCVD , de novo ASCVD , and recurrent ASCVD , respectively . A nonlinear model did not fit the data better than a linear model . CONCLUSIONS The level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study BACKGROUND Blood pressure shows an inverse association with mortality in patients with chronic kidney disease ( CKD ) on dialysis .  It is unclear if the same phenomenon exists in patients with CKD not yet on dialysis . METHODS We examined the association of  systolic ( SBP ) and diastolic ( DBP ) blood pressure  with  all-cause mortality  in a historical prospect i ve cohort of 860 patients ( age 68.1+/-10.1 years , 99.1 % male , 24.4 % black ) with estimated glomerular filtration rate ( GFR ) < 60 ml/min/1.73 m2 . We used Cox models to adjust for the effects of age , race , diabetes mellitus , atherosclerotic cardiovascular disease ( ASCVD ) , congestive heart failure , smoking , antihypertensive medications , body mass index , GFR , albumin , cholesterol , haemoglobin and proteinuria . To examine the role of comorbidities , we performed subgroup analyses based on prevalent ASCVD status and level of estimated GFR . RESULTS Higher SBP and higher DBP were both associated with lower mortality [ adjusted hazard ratio ( 95 % confidence interval ) for SBP 133 - 154 , 155 - 170 and > 170 mmHg , compared with < 133 mmHg , respectively : 0.61 ( 0.44 - 0.85 ) , 0.62 ( 0.45 - 0.87 ) and 0.68 ( 0.49 - 0.96 ) ; and for DBP 65 - 75 , 76 - 86 and > 86 mmHg , compared with < 65 mmHg : 0.85 ( 0.62 - 1.18 ) , 0.72 ( 0.52 - 1.00 ) and 0.60 ( 0.41 - 0.86 ) ] . The same association was present for both SBP and DBP only in subgroups with GFR < or = 30 ml/min/1.73 m2 and for DBP only in the subgroup with ASCVD . CONCLUSIONS Lower blood pressure is associated with higher mortality in patients with moderate to severe CKD , but interactions with kidney function and with ASCVD suggest that blood pressure may play a surrogate rather than a causative role in this association AIM Our objective was to investigate the effects and tolerability of fixed-dose combination therapy on blood pressure and LDL in adults without elevated blood pressure or lipid levels . METHODS This was a double-blind r and omised placebo-controlled trial in residents of Kalaleh , Golestan , Iran . Following an 8-week placebo run-in period , 475 participants , aged 50 to 79 years , without cardiovascular disease , hypertension or hyperlipidaemia were r and omised to fixed-dose combination therapy with aspirin 81 mg , enalapril 2.5 mg , atorvastatin 20 mg and hydrochlorothiazide 12.5 mg ( polypill ) or placebo for a period of 12 months . The primary outcomes were changes in LDL-cholesterol , systolic and diastolic blood pressure and adverse reactions . Analysis was by intention-to-treat basis . RESULTS At baseline , there were differences in systolic blood pressure ( 6 mmHg ) . Taking account of baseline differences , at 12 months , polypill was associated with statistically significant reductions in blood pressure ( 4.5/1.6 mmHg ) and LDL-cholesterol ( 0.46 mmol/l ) . The study drug was well tolerated , but result ed in the modest reductions in blood pressure and lipid levels . CONCLUSION The effects of the polypill on blood pressure and lipid levels were less than anticipated , raising questions about the reliability of the reported compliance . There is a case for a fully powered trial of a polypill for the prevention of cardiovascular disease BACKGROUND AND AIMS Patients with established coronary artery disease ( CAD ) are likely to receive a combination of aspirin , a statin , and blood pressure (BP)-lowering agents . Combining these pharmacologic agents into a cardiovascular combination pill , such as a polypill , could be considered to reduce prescription gaps and nonadherence in high-risk patients . We aim ed to evaluate the effect of the concomitant use of aspirin , a statin , and BP-lowering agent(s ) in patients with CAD on vascular morbidity and mortality  in current clinical practice in an observational study to provide insights in the combination pill concept related to feasibility and applicability . METHODS In total , 2,706 patients with CAD enrolled in the Second Manifestations of ARTerial disease study were followed for the occurrence of a subsequent vascular event ( ie , myocardial infa rct ion , ischemic cerebrovascular accident , vascular death ) and all-cause mortality . The relationship between combination therapy and cardiovascular events and all-cause mortality was assessed using Cox proportional hazards regression models to calculate hazards ratios ( HRs ) with a 95 % CI . Both covariate and propensity score adjusting methods were used to reduce confounding by indication . RESULTS A combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) was used by 67 % of the patients . During a median of 5.0 years ( interquartile range 2.4 - 10.2 years ) , 347 vascular events occurred and 162 patients died . Combination therapy with aspirin , statin , and ≥1 BP-lowering agent was associated with a lower risk of myocardial infa rct ion ( HR 0.68 , 95 % CI 0.49 - 0.96 ) , ischemic cerebrovascular accident ( HR 0.37 , 95 % CI 0.16 - 0.84 ) , composite vascular end point ( HR 0.66 , 95 % CI 0.49 - 0.88 ) , vascular mortality ( HR 0.53 , 95 % CI 0.33 - 0.85 ) , and all-cause mortality ( HR 0.69 , 95 % CI 0.49 - 0.96 ) compared with the absence of combination therapy , after adjusting for confounding covariates in a propensity score . The use of 1 or only 2 components of combination therapy was associated with a higher risk for cardiovascular events compared with the combined use of aspirin , a statin , and ≥1 BP-lowering agent(s ) . CONCLUSION Two-thirds of the patients with CAD use a combination of aspirin , a statin , and ≥1 BP-lowering agent(s ) , components of a cardiovascular fixed-dose combination pill . Combination therapy with these agents is associated with a lower risk of vascular events and total mortality . Although treatment effect in observational studies should be interpreted with caution , the results of this study support supposed benefits from combination therapy . However , the effect of fixed-dose combination pill on clinical outcome needs to be demonstrated in r and omized clinical trials Introduction This paper describes a planned process evaluation of the Use of a Multidrug Pill In Reducing Cardiovascular Events ( UMPIRE ) trial , one of several r and omised clinical trials taking place globally to assess the potential of cardiovascular drugs as a fixed-dose combination ( polypill ) in cardiovascular disease prevention . A fixed-dose combination may be a promising strategy for promoting adherence to medication ; alleviating pill burden through simplifying regimens and reducing cost . This process evaluation will complement the UMPIRE trial by using qualitative research methods to inform underst and ing of the complex interplay of factors that underpin trial outcomes . Methods A series of semistructured , in-depth interviews with local health professionals and UMPIRE trial participants in India and the UK will be undertaken . The aim is to underst and their views and experiences of the trial context and of day-to-day use of medications more generally . The grounded theory approach will be used to analyse data and help inform the processes of the UMPIRE trial . Ethics and dissemination The study has received ethical approval for all sites in the UK and India where trial participant interviews will be undertaken . The process evaluation will help inform and enhance the underst and ing of the UMPIRE trial results and its applicability to clinical practice as well as shaping policy regarding strategies for improving cardiovascular medication adherence Background Most individuals at high cardiovascular disease ( CVD ) risk worldwide do not receive any or optimal preventive drugs . We aim ed to determine whether fixed dose combinations of generic drugs ( ‘ polypills ’ ) would promote use of such medications . Methods We conducted a r and omized , open-label trial involving 623 participants from Australian general practice s. Participants had established CVD or an estimated five-year CVD risk of ≥15 % , with indications for antiplatelet , statin and ≥2 blood pressure lowering drugs ( ‘ combination treatment ’ ) . Participants r and omized to the ‘ polypill-based strategy ’  received a polypill containing aspirin 75 mg , simvastatin 40 mg , lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg . Participants r and omized to ‘ usual care ’ continued with separate medications and doses as prescribed by their doctor . Primary outcomes were self-reported combination treatment use , systolic blood pressure and total cholesterol . Results After a median of 18 months , the polypill-based strategy was associated with greater use of combination treatment ( 70 % vs. 47 % ; relative risk 1.49 , ( 95 % confidence interval ( CI ) 1.30 to 1.72 ) p < 0.0001 ; number needed to treat = 4.4 ( 3.3 to 6.6 ) ) without differences in systolic blood pressure ( −1.5 mmHg ( 95 % CI −4.0 to 1.0 ) p = 0.24 ) or total cholesterol ( 0.08 mmol/l ( 95 % CI −0.06 to 0.22 ) p = 0.26 ) . At study end , 17 % and 67 % of participants in polypill and usual care groups , respectively , were taking  atorvastatin  or rosuvastatin . Conclusion Provision of a polypill improved self-reported use of indicated preventive treatments . The lack of differences in blood pressure and cholesterol may reflect limited study power , although for cholesterol , improved statin use in the polypill group counter-balanced use of more potent statins with usual care BACKGROUND Identification of the population at high risk of developing  atherosclerotic cardiovascular disease ( ASCVD ) is critical for its prevention . The aim of the present study was to evaluate the use of  fasting blood glucose ( FBG )  to predict ASCVD . METHODS In all , 18 610 participants , aged 35 - 74 years at enrollment , were included in this prospect i ve study . Baseline information was collected using a st and ardized question naire , physical examinations , and laboratory tests . During follow-up , disease status and vital information were up date d. Cox proportional hazards regression analysis was used to estimate associations , with normal FBG ( 70 - 99 mg/dL ) as the reference group . Anthropometric measurements , socioeconomic status , and conventional cardiovascular risk factors were included in the multivariate-adjusted model . RESULTS After 7.8 years follow-up ( 145 223 person-years ) , there were 519 cases of ASCVD . The multivariate-adjusted hazard ratios ( HR ) , with 95 % confidence intervals ( CI ) , for ASCVD in patients with low FBG ( < 70 mg/dL ) , impaired fasting glucose ( IFG ; 100 - 125 mg/dL ) , and diabetes ( ≥126 mg/dL , use of antidiabetic medication and /or self-report ) were 1.35 ( 0.84 , 2.15 ) , 1.02 ( 0.81 , 1.27 ) , and 1.68 ( 1.26 , 2.23 ) , respectively . Although IFG was associated with the development of diabetes ( multivariate-adjusted HR 3.67 ; 95 % CI 3.20 , 4.21 ) , it was only associated with incident ASCVD in the univariate model ( HR 1.52 ; 95 % CI 1.23 , 1.88 ) . The association of diabetes with coronary heart disease was more pronounced than that with stroke . Gender and residential differences were also identified . CONCLUSIONS In the present study , IFG was associated with the development of diabetes but not incident ASCVD . Prevention strategies to reduce the development of diabetes in people with IFG are critical to improve cardiovascular health Background : Dapagliflozin is a sodium‐glucose co‐transporter‐2 ( SGLT‐2 ) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus ( T2DM ) by promoting glycosuria via inhibiting urinary glucose reabsorption . In addition to improving blood glucose control , treatment with dapagliflozin results in glucose‐induced osmotic diuresis , weight loss , and blood pressure lowering . Previous trials of SGLT‐2 inhibitors showed reductions in cardiovascular ( CV ) events , including CV death and hospitalization for heart failure , and ischemic events in patients with atherosclerotic cardiovascular disease ( ASCVD ) . Research design and methods : DECLARE – TIMI 58 ( NCT01730534 ) is a phase 3b r and omized , double‐blind , placebo‐controlled trial design ed to evaluate the CV safety and efficacy of dapagliflozin that has completed r and omization of 17,160 patients with T2DM and a history of either established ASCVD ( n = 6,971 ) or multiple risk factors for ASCVD ( n = 10,189 ) . Patients were r and omized in a 1:1 fashion to dapagliflozin 10 mg or matching placebo . The primary safety outcome is the time to the first event of the composite of CV death , myocardial infa rct ion , or ischemic stroke ( major adverse cardiovascular events ; MACEs ) . The co‐ primary efficacy outcomes are the composite of CV death , myocardial infa rct ion , or ischemic stroke and the composite of CV death or hospitalization for heart failure . This event‐driven trial will continue until at least 1,390 subjects have a MACE outcome , thereby providing > 99 % power to test for the primary outcome of safety  of dapagliflozin measured by rejecting the hypothesis that the upper bound of the CI > 1.3 for the primary outcome of MACE , as well as 85 % power to detect a 15 % relative risk reduction in MACE and an estimated 87 % power to detect a 20 % reduction in the composite of CV death or hospitalization for heart failure at a 1‐sided & agr ; level of .0231 . Conclusion : The DECLARE – TIMI 58 trial is testing the hypotheses that dapagliflozin is safe ( does not increase ) and may reduce the occurrence of major CV events . DECLARE – TIMI 58 is the largest study to address this question with an SGLT‐2 inhibitor in patients with T2DM and with established CV disease and without CV disease but with multiple risk factors Background : The accurate assessment of individual risk can be of great value to guiding and facilitating the prevention of atherosclerotic cardiovascular disease ( ASCVD ) . However , prediction models in common use were formulated primarily in white population s. The China-PAR project ( Prediction for ASCVD Risk in China ) is aim ed at developing and validating 10-year risk prediction equations for ASCVD from 4 contemporary Chinese cohorts . Methods : Two prospect i ve studies followed up together with a unified protocol were used as the derivation cohort to develop 10-year ASCVD risk equations in 21 320 Chinese participants . The external validation was evaluated in 2 independent Chinese cohorts with 14 123 and 70 838 participants . Furthermore , model performance was compared with the Pooled Cohort Equations reported in the American College of Cardiology/American Heart Association guideline . Results : Over 12 years of follow-up in the derivation cohort with 21 320 Chinese participants , 1048 subjects developed a first ASCVD event . Sex-specific equations had C statistics of 0.794 ( 95 % confidence interval , 0.775–0.814 ) for men and 0.811 ( 95 % confidence interval , 0.787–0.835 ) for women . The predicted rates were similar to the observed rates , as indicated by a calibration & khgr;2 of 13.1 for men ( P=0.16 ) and 12.8 for women ( P=0.17 ) . Good internal and external validations of our equations were achieved in subsequent analyses . Compared with the Chinese equations , the Pooled Cohort Equations had lower C statistics and much higher calibration & khgr;2 values in men . Conclusions : Our project developed effective tools with good performance for 10-year ASCVD risk prediction among a Chinese population that will help to improve the primary prevention and management of cardiovascular disease
The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain .
A limited number of trials reported these outcomes , and the included trials were primarily design ed to observe changes in ASCVD risk factor levels rather than clinical events , which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials .
Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo , active comparator , or usual care but may be associated with improved adherence to a multidrug regimen .
Ongoing , longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes
BACKGROUND Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death and disability worldwide , yet ASCVD risk factor control and secondary prevention rates remain low .
A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill , or polypill , has been proposed as one strategy to reduce the global burden of ASCVD .
OBJECTIVES To determine the effect of fixed-dose combination therapy on all-cause mortality , fatal and non-fatal ASCVD events , and adverse events .
We also sought to determine the effect of fixed-dose combination therapy on blood pressure , lipids , adherence , discontinuation rates , health-related quality of life , and costs .