Risk Of Major Coronary Events Research Articles

European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

European and US guideline-based statin eligibility, genetically predicted coronary artery disease, and the risk of major coronary events

Abstract Objectives To investigate whether polygenic risk score for coronary artery disease (CAD-PRS) can guide the initiation of lipid-lowering treatment as well as deferral beyond the statin eligibility criteria. Methods 311,799 individuals aged 40 to 73 years and free of atherosclerotic cardiovascular disease (ASCVD), diabetes, chronic kidney disease, and lipid-lowering treatment at baseline were included from the UK Biobank. Participants were categorized by statin eligibility using the European and US guidelines on statin use. Results For a median (IQR) follow-up of 11.9 (11.2-12.6) years, 8,196 individuals experienced major coronary events. CAD-PRS added to European-SCORE2 and US-PCE models identified 18% and 12% of individuals with class II indication for statin use whose risk of major coronary events were same or higher than the average risk of those with class I indication and 16% and 12% of individuals with class I indication whose major coronary event risks were same or lower than the average risk of those with class II indication. For ASCVD events, CAD-PRS added to European-SCORE2 and US-PCE models resulted in a net reclassification improvement of 13.6% (95% CI 11.8 to 15.5) and 14.7% (95% CI 13.1 to 16.3) among class I indicated, 10.8% (95% CI 9.6 to 12.0) and 15.3% (95% CI 13.2 to 17.5) among class II indicated, and 0.9% (95% CI 0.6 to 1.3) and 3.6% (95% CI 3.0 to 4.2) among class III indicated individuals. Conclusions CAD-PRS may guide statin initiation as well as deferral among individuals with class I and class II indication for statin use as defined by the European and US guidelines. However, the CAD-PRS had little clinical utility among individuals who were not eligible for statins.

Combining family history of coronary heart disease and individual genetic predisposition to accurately predict the lifetime risk of major coronary events

Combining family history of coronary heart disease and individual genetic predisposition to accurately predict the lifetime risk of major coronary events

18F-sodium fluoride positron emission tomography following coronary computed tomography angiography in predicting long-term coronary events: a 5-year follow-up study.

The predictive value of 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) in combination with coronary computed tomography (CT) angiography (CCTA) for future coronary events has attracted interest. We evaluated the potential of 18F-NaF PET/CT following CCTA to predict major coronary events (MACE) during a 5-year follow-up period. Forty patients with coronary atherosclerotic lesions detected on CCTA underwent 18F-NaF PET/CT examination. Each lesion was evaluated for luminal stenosis and high-risk plaque (HRP) with < 30 Hounsfield units and a > 1.1 remodeling index on CCTA. Focal 18F-NaF uptake in each lesion was quantified using the maximum tissue-to-background ratio (TBRmax), and the maximum TBRmax per patient (M-TBRmax) was determined. We followed MACE (cardiac death, acute coronary syndrome, and/or coronary revascularization > 6months after 18F-NaF PET/CT) for 5years. In total, 142 coronary lesions were analyzed. Eleven patients experienced any MACE. Patients with MACE showed a higher M-TBRmax than those without (1.40 ± .19 vs. 1.18 ± .18, P = .0011), and the optimal M-TBRmax cutoff to predict MACE was 1.29. Patients with M-TBRmax of ≥ 1.29 had a higher risk of MACE than those with lower values (P = .012, log-rank test), whereas patients with obstructive stenosis and those with HRP did not. Multivariate Cox proportional analysis adjusted for age, sex, coronary risk factors, and CCTA findings showed that M-TBRmax of ≥ 1.29 remained an independent predictor of 5-year MACE (hazard ratio, 5.4; 95% confidence interval, 1.1-25.4; P = .034). 18F-NaF PET/CT following CCTA provides useful strategies to predict 5-year MACE.

Combining family history of coronary heart disease and individual genetic predisposition to predict the risk of major coronary events: Selected Abstract - SITeCS Congress 2022

Background: Inherited predisposition to atherosclerosis leads to higher risk for developing coronary heart disease (CHD). There are mainly two ways to conceptualize inherited risk of CHD: family history and polygenic predisposition. We aimed at assessing the impact of family history of CHD and genetic predisposition in predicting the individual lifetime risk of major coronary events (MCE). Methods: Using adjusted Cox proportional hazard models, we estimated the lifetime risk of MCE associated with parental family history of CHD and individual genetic predisposition (estimated by a polygenic risk score including 350 variants). Results: A total of 445,744 UK-Biobank participants were included in the study (mean age 57 years; 54.3% females). Having one parent with a history of CHD increased the lifetime risk of MCE by 75% (HR 1.75, 95%CI 1.70-1.82). Having both parents with a history of CHD further increased the risk (HR 2.78, 95%CI 2.64-2.92) Similarly, a dose-dependent step-wise increase in MCE risk was observed moving from the lowest to the highest decile of the polygenic score. Compared to subjects without family history of CHD and with average level of the polygenic score, having a parental history of CHD determined an increase in lifetime risk of MCE (HR 1.90, 95%CI 1.82-1.98) comparable to belonging to the highest decile of the polygenic score (HR 1.89, 95%CI 1.76-2.02). However, if subjects present both parents with family history of CHD and a very high polygenic predisposition, the risk was even higher (HR 3.54, 95%CI 3.34-3.75), suggesting an additive contribution to the characterization of the lifetime risk. Conclusions: We described the addictive impact of family history of CHD and individual polygenic predisposition in predicting lifetime risk of MCE. In order to identify subjects at higher risk of having an early event, it is essential to retrieve information about both these hereditary components.

Associations of Modified Healthy Aging Index With Major Adverse Cardiac Events, Major Coronary Events, and Ischemic Heart Disease.

Background The Healthy Aging Index (HAI) has been regarded as useful in capturing the health status of multiple organ systems. However, to what extent the HAI is associated with major cardiovascular events remains largely unknown. The authors constructed a modified HAI (mHAI) to quantify the association of physiological aging with major vascular events and explored how the effects of a healthy lifestyle can modify this association. Methods and Results The participants with either missing values of any individual mHAI component or major illnesses such as heart attack, angina and stroke, and self-reported cancer at baseline were excluded. The mHAI components include systolic blood pressure, reaction time, forced vital capacity, serum cystatin c, and serum glucose. The authors used Cox proportional hazard models to quantify the association of mHAI with major adverse cardiac events, major coronary events, and ischemic heart disease. Cumulative incidence at 5 and 10 years was estimated, and joint analyses were stratified by age group and 4 mHAI categories. The mHAI was significantly correlated with major cardiovascular events, which is a better reflection of the aging level of the body than chronological age. An mHAI was calculated in 338 044 participants aged 38 to 73 years in the UK Biobank. Each point increase in the mHAI was associated with a 44% higher risk of major adverse cardiac events (adjusted hazard ratio [aHR], 1.44 [95% CI, 1.40-1.49]), 44% higher risk of major coronary events (aHR, 1.44 [95% CI, 1.40-1.48]), and 36% higher risk of ischemic heart disease (aHR, 1.36 [95% CI, 1.33-1.39]). The percentage of population-attribution risk was 51% (95% CI, 47-55) for major adverse cardiac events, 49% (95% CI, 45-53) for major coronary events, and 47% (95% CI, 44-50) for ischemic heart disease, which means that a substantial portion of these events could be prevented. Systolic blood pressure was the factor most significantly associated with major adverse cardiac events (aHR, 1.94 [95% CI, 1.82-2.08]; percentage of population-attribution risk, 36%), major coronary events (aHR, 2.01 [95% CI, 1.85-2.17]; percentage of population-attribution risk, 38%), and ischemic heart disease (aHR, 1.80 [95% CI, 1.71-1.89]; percentage of population-attribution risk, 32%). A healthy lifestyle significantly attenuated mHAI associations with incidence of vascular events. Conclusions Our findings indicate that higher mHAI is associated with increased major vascular events. A healthy lifestyle may attenuate these associations.

Risk Factors of Cardiovascular Pathology in Patients with Gout.

To determine the frequency and assess the risk of cardiovascular disease in patients suffering from gout. Gout is a sign of disturbed metabolism, which is associated with cardiovascular diseases (CVD). Soaring mortality is associated with a lot of risk factors and comorbid conditions, which have to be dealt with the help of scientists and practitioners. The following retrospective study included 218 patients suffering from gout according to the criteria of S.L. Wallace. The risk of major coronary events was calculated via the SCORE scale. Arterial hypertension and BMI > 25 kg / m2 (90.8%) have prevailed among the respondents. Increased level of total cholesterol (TC) was detected in 63.8% cases, decreased level of highdensity lipoproteins - in 71.6%, and hypertriglyceridemia - in 60.5% relevantly. 175 patients (80.3%) had high cardiovascular risk (estimated more than 5%). 43 (19.7%) of them had a low and medium risk of developing fatal CVD (1-4%). The high share of patients suffering from gout was endangered with cardiovascular pathology. The most frequently matched risk factors among patients suffering from gout are an increase in BMI> 25 kg/m2 (90.8%) and dyslipidemia.

Risk Factors, Use of Preventive Drugs, and Cardiovascular Events in Diabetes Mellitus: The PURE Türkiye Cohort.

The risk of cardiovascular disease is correlated with the frequency and control of associated risk factors in diabetes mellitus and may vary according to country. We evaluated risk factors for cardiovascular disease, cardiovascular events, and the use of preventive medications in patients with diabetes mellitus using the Prospective Urban and Rural Epidemiological Türkiye cohort. Patients with diabetes mellitus versus without diabetes mellitus were compared for risk factors, cardioprotective drugs (angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists, statins, and antiplatelets), and cardiovascular events. The primary outcome was major cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, or heart failure). Among 4041 participants, 549 (13.6%) had diabetes mellitus. The mean age (54.8 ± 8.4 vs. 49.3 ± 9.0 years, P <.001) and proportion of women (65.4% vs. 59.9%, P =.014) were higher in diabetics compared with non-diabetics. Hypertension, history of coronary heart disease, and use of statin, antiplatelets, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists were more common in diabetics; however, the use of these medications at baseline was lower than optimal even in patients with diabetes mellitus and concomitant coronary heart disease (statin 31.2%, antiplatelets 46.9%, and angiotensin-converting enzyme inhibitors or angiotensin-II receptor antagonists 54.7%). During 11.5 years of follow-up, major cardiovascular events occurred in 288 (7.1%) patients, and the risk was higher in diabetics [hazard ratio (95% confidence interval) 1.71 (1.30-2.24); P <.001]. The increase in the risk of future events was comparable for those with diabetes mellitus alone without cardiovascular disease [hazard ratio 1.62 (1.20-2.20)] versus those with cardiovascular disease alone without diabetes mellitus [hazard ratio 1.31 (0.83-2.07)] and was additive in those with both conditions [hazard ratio 2.79 (1.65-4.69)]. The risk of major coronary events (myocardial infarction, angina, percutaneous, or surgical coronary intervention) was also higher in diabetes mellitus [hazard ratio 1.64 (1.26-2.15); P <.001]. Patients with diabetes mellitus have a higher risk of major cardiovascular events, and the risk is comparable to that observed in those with cardiovascular disease but no diabetes mellitus. The use of preventive medicines for cardiovascular diseases is disturbingly low in diabetics.

The Prevalence Of Aspirin Use As A Primary Prevention In Hypertensive Patients In Tikrit City

The aspirin use for secondary prevention of cardiovascular disease (CVD) is strongly supported and is well established but its use for primary prevention of cardiovascular events is a source of major debate due to that persons without a previous history of CVD are less likely to have future cardiovascular events, so there is unclear balance between benefits of aspirin to decrease the risk as primary prevention and harms of increase risk of both gastrointestinal bleeding and hemorrhagic stroke. This was reflected in international trails and guidelines. In this study, to balance the risk and benefit of using aspirin for primary prevention of CVD , and depend on trials and guidelines , the using of aspirin is more beneficial and indicated in patients with high ASCVD risk (e.g., as calculated by ASCVD risk score ((which used to calculate the 10 years risk of major coronary events in adults)) as &gt;10% , or depending on the presence of certain ASCVD risk factors) , in patients with age between 40-70 and low risk of bleeding. This study aimed to estimate the prevalence of aspirin use in hypertensive patients for primary prevention of cardiovascular diseases. One hundred fifty hypertensive patients (75 male) and (75 female) attending the outpatient clinic in Saladin general hospital in Tikrit city were included in this study from January 2018 to December 2019. Considering these parameters (age, total cholesterol level, , systolic blood pressure (BP), high density lipoprotein cholesterol (HDL), and smoking) in every patients.

Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels.

Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.

Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial

BackgroundBiomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood. ObjectivesWe examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures. MethodsFOURIER was a randomized trial of the proprotein convertase subtilisin–kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro–B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL). ResultsWhen patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HRadj: 1.57 [95% CI: 1.38-1.78]; high score: HRadj: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HRadj: 1.33 [95% CI: 1.06-1.67]; high score: HRadj: 2.07 [95% CI: 1.52-2.83]) and its components (Ptrend <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each). ConclusionsA biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk coronary anatomy at the time of revascularization. These findings provide insight into the relationships between cardiovascular biomarkers, coronary anatomical complexity, and incident clinical events. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633)

Is the risk of atherosclerotic cardiovascular disease different between genotype determined or measured Lp(a) levels?

Background and Aims : Lp(a) concentration has been associated to increased risk of atherosclerotic cardiovascular disease (ASCVD). Whether ASCVD risk varies between LPA genotype or measured Lp(a) levels is still unknown.Methods: A total of 445,744 participants enrolled in the UK-Biobank with complete genetic and principal component data were included in the study. For each participant, we calculated the LPA genetic risk score by summing the number of risk-increasing alleles inherited at rs3798220 and rs10455872 variants, weighted by the effect size of each allele. The primary outcome was major coronary event (MCE), a composite of fatal or non-fatal myocardial infarction, or coronary revascularization. Using adjusted Cox proportional hazards models and Kaplan-Meier curves, we compared the cumulative lifetime risk of MCE among subjects with different LPA genotype and measured Lp(a) concentrations.Results: Participants with one copy of either rs10455872 or rs3798220 had a hazard ratio (HR) for MCE of 1.47 (95%CI: 1.42-1.51) compared with wild-type subjects (median Lp(a): 146.3 nmol/L and 13.6 nmol/L, respectively). Stratifying the population according to measured Lp(a) concentrations comparable to those observed for the genetic risk score, we found similar rate of incident MCE for the same Lp(a) change (HR 1.47, 95%CI: 1.41-1.53). Even among subjects with the same LPA genotype, increasing quintiles of Lp(a) concentration were associated with a step-wise increase in MCE risk.Conclusions: Our results demonstrated that LPA genetic risk score and measured Lp(a) concentrations provide comparable risk prediction for incident MCE. In terms of cardiovascular risk prediction, it is reasonable to rely on clinically measured Lp(a) levels, regardless of genotype. Background and Aims : Lp(a) concentration has been associated to increased risk of atherosclerotic cardiovascular disease (ASCVD). Whether ASCVD risk varies between LPA genotype or measured Lp(a) levels is still unknown. Methods: A total of 445,744 participants enrolled in the UK-Biobank with complete genetic and principal component data were included in the study. For each participant, we calculated the LPA genetic risk score by summing the number of risk-increasing alleles inherited at rs3798220 and rs10455872 variants, weighted by the effect size of each allele. The primary outcome was major coronary event (MCE), a composite of fatal or non-fatal myocardial infarction, or coronary revascularization. Using adjusted Cox proportional hazards models and Kaplan-Meier curves, we compared the cumulative lifetime risk of MCE among subjects with different LPA genotype and measured Lp(a) concentrations. Results: Participants with one copy of either rs10455872 or rs3798220 had a hazard ratio (HR) for MCE of 1.47 (95%CI: 1.42-1.51) compared with wild-type subjects (median Lp(a): 146.3 nmol/L and 13.6 nmol/L, respectively). Stratifying the population according to measured Lp(a) concentrations comparable to those observed for the genetic risk score, we found similar rate of incident MCE for the same Lp(a) change (HR 1.47, 95%CI: 1.41-1.53). Even among subjects with the same LPA genotype, increasing quintiles of Lp(a) concentration were associated with a step-wise increase in MCE risk. Conclusions: Our results demonstrated that LPA genetic risk score and measured Lp(a) concentrations provide comparable risk prediction for incident MCE. In terms of cardiovascular risk prediction, it is reasonable to rely on clinically measured Lp(a) levels, regardless of genotype.

A Randomized Controlled Trial Evaluating Outcome Impact of Cilostazol in Patients with Coronary Artery Disease or at a High Risk of Cardiovascular Disease.

Previous studies found that cilostazol has a favorable effect on glucose and lipid homeostasis, endothelial function, atherosclerosis, and vasculo-angiogenesis. However, it is poorly understood whether these effects can translate into better clinical outcomes. This study investigated the outcome effect of cilostazol in patients with coronary artery disease (CAD) or at a high risk of cardiovascular (CV) disease. We conducted a randomized, double-blind, placebo-controlled trial involving 266 patients who received cilostazol, 200 mg/day (n = 134) or placebo (n = 132). Pre-specified clinical endpoints including composite major adverse cardiovascular events (MACE) (CV death, non-fatal myocardial infarct, non-fatal stroke, hospitalization for heart failure, or unplanned coronary revascularization), the composite major coronary event (MCE) and major adverse CV and cerebrovascular event (MACCE), were prospectively assessed. The mean duration of follow-up was 2.9 years. Relative to placebo, cilostazol treatment had a borderline effect on risk reduction of MACE (hazard ratio [HR], 0.67; 95% confidence interval (CI), 0.34–1.33), whereas the beneficial effect in favor of cilostazol was significant in patients with diabetes mellitus or a history of percutaneous coronary intervention (p for interaction, 0.02 and 0.06, respectively). Use of cilostazol, significantly reduced the risk of MCE (HR, 0.38; 95% CI, 0.17–0.86) and MACCE (HR, 0.47; 95% CI, 0.23–0.96). A significantly lower risk of angina pectoris (HR, 0.38; 95% CI, 0.17–0.86) was also observed in the cilostazol group. After multi-variable adjustment, cilostazol treatment independently predicted a lower risk of MCE. In conclusion, these results suggest cilostazol may have beneficial effects in patients with CAD or at a high risk of CV disease.

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease.

AimsREVEAL was the first randomized controlled trial to demonstrate that adding cholesteryl ester transfer protein inhibitor therapy to intensive statin therapy reduced the risk of major coronary events. We now report results from extended follow-up beyond the scheduled study treatment period.Methods and resultsA total of 30 449 adults with prior atherosclerotic vascular disease were randomly allocated to anacetrapib 100 mg daily or matching placebo, in addition to open-label atorvastatin therapy. After stopping the randomly allocated treatment, 26 129 survivors entered a post-trial follow-up period, blind to their original treatment allocation. The primary outcome was first post-randomization major coronary event (i.e. coronary death, myocardial infarction, or coronary revascularization) during the in-trial and post-trial treatment periods, with analysis by intention-to-treat. Allocation to anacetrapib conferred a 9% [95% confidence interval (CI) 3–15%; P = 0.004] proportional reduction in the incidence of major coronary events during the study treatment period (median 4.1 years). During extended follow-up (median 2.2 years), there was a further 20% (95% CI 10–29%; P < 0.001) reduction. Overall, there was a 12% (95% CI 7–17%, P < 0.001) proportional reduction in major coronary events during the overall follow-up period (median 6.3 years), corresponding to a 1.8% (95% CI 1.0–2.6%) absolute reduction. There were no significant effects on non-vascular mortality, site-specific cancer, or other serious adverse events. Morbidity follow-up was obtained for 25 784 (99%) participants.ConclusionThe beneficial effects of anacetrapib on major coronary events increased with longer follow-up, and no adverse effects emerged on non-vascular mortality or morbidity. These findings illustrate the importance of sufficiently long treatment and follow-up duration in randomized trials of lipid-modifying agents to assess their full benefits and potential harms.Trial registrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 48678192; ClinicalTrials.gov No. NCT01252953; EudraCT No. 2010-023467-18.

Diabetes status modifies the long-term effect of lipoprotein-associated phospholipase A2 on major coronary events

Aims/hypothesisLipoprotein-associated phospholipase A2 (Lp-PLA2) activity has an independent prognostic association with major coronary events (MCE). However, no study has investigated whether type 2 diabetes status modifies the effect of Lp-PLA2 activity or inhibition on the risk of MCE. We investigate the interaction between diabetes status and Lp-PLA2 activity with risk of MCE. Subsequently, we test the resulting hypothesis that diabetes status will play a role in modifying the efficacy of an Lp-PLA2 inhibitor.MethodsA retrospective cohort study design was utilised in two study populations. Discovery analyses were performed in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) cohort based in Scotland, UK. Participants were categorised by type 2 diabetes control status: poorly controlled (HbA1c ≥ 48 mmol/mol or ≥6.5%) and well-controlled (HbA1c < 48 mmol/mol or <6.5%) diabetes (n = 7420). In a secondary analysis of the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial of Lp-PLA2 inhibitor (darapladib) efficacy, 15,828 participants were stratified post hoc by type 2 diabetes diagnosis status (diabetes or no diabetes) at time of recruitment. Lp-PLA2 activity was then divided into population-specific quartiles. MCE were determined from linked medical records in GoDARTS and trial records in STABILITY. First, the interaction between diabetes control status and Lp-PLA2 activity on the outcome of MCE was explored in GoDARTS. The effect was replicated in the placebo arm of STABILITY. The effect of Lp-PLA2 on MCE was then examined in models stratified by diabetes status. This helped determine participants at higher risk. Finally, the effect of Lp-PLA2 inhibition was assessed in STABILITY in the higher risk group. Cox proportional hazards models adjusted for confounders were used to assess associations.ResultsIn GoDARTS, a significant interaction between increased Lp-PLA2 activity (continuous and quartile divided) and diabetes control status was observed in the prediction of MCE (p < 0.0001). These effects were replicated in the placebo arm of STABILITY (p < 0.0001). In GoDARTS, stratified analyses showed that, among individuals with poorly controlled diabetes, the hazards of MCE for those with high (Q4) Lp-PLA2 activity was 1.19 compared with individuals with lower (Q1–3) Lp-PLA2 activity (95% CI 1.11, 1.38; p < 0.0001) and 1.35 (95% CI 1.16, 1.57; p < 0.0001) when compared with those with the lowest activity (Q1). Those in the higher risk group were identified as individuals with the highest Lp-PLA2 activity (Q4) and poorly controlled diabetes or diabetes. Based on these observations in untreated populations, we hypothesised that the Lp-PLA2 inhibitor would have more benefit in this higher risk group. In this risk group, Lp-PLA2 inhibitor use was associated with a 33% reduction in MCE compared with placebo (HR 0.67 [95% CI 0.50, 0.90]; p = 0.008). In contrast, Lp-PLA2 inhibitor showed no efficacy in individuals with low activity, regardless of diabetes status, or among those with no baseline diabetes and high Lp-PLA2 activity.Conclusions/interpretationThese results support the hypothesis that diabetes status modifies the association between Lp-PLA2 activity and MCE. These results suggest that cardiovascular morbidity and mortality associated with Lp-PLA2 activity is especially important in patients with type 2 diabetes, particularly those with worse glycaemic control. Further investigation of the effects of Lp-PLA2 inhibition in diabetes appears warranted.Data availabilitySTABILITY trial data are available from clinicaltrials.gov repository through the GlaxoSmithKline clinical study register https://clinicaltrials.gov/ct2/show/NCT00799903. GoDARTS datasets generated during and/or analysed during the current study are available following request to the GoDARTS Access Managements Group https://godarts.org/scientific-community/.Graphical abstract

Type 2 Diabetes and Myocardial Infarction: Recent Clinical Evidence and Perspective.

Type 2 diabetes mellitus (T2DM) and its complications are seriously affecting public health worldwide. Myocardial infarction (MI) is the primary cause of death in patients with T2DM. T2DM patients without a history of coronary artery disease (CAD) have the same risk of major coronary events as those with CAD; T2DM patients with a history of MI have >40% risk of recurrence of MI. Thus, CAD in patients with T2DM needs to be treated actively to reduce the risk of MI. The cardiology community focused on the role of T2DM in the development of CAD and on the related issues of T2DM and MI with respect to comorbidities, prognosis, drug therapy, and heredity. In this mini review, the latest progress of clinical evidence-based research between T2DM and MI in recent years was reviewed, and the possible research directions in this field were considered and prospected.

Effect of Kidney Function on Relationships between Lifestyle Behaviors and Mortality or Cardiovascular Outcomes: A Pooled Cohort Analysis.

Adherence to healthy behaviors reduces risks of cardiovascular disease and death in the general population. However, among people with kidney disease, a group at higher risk for cardiovascular disease, such benefits have not been established. We pooled data from three cohort studies with a total of 27,271 participants. Kidney function was categorized on the basis of eGFR (≥60, 45 to <60, and <45 ml/min per 1.73 m2). We used proportional hazard frailty models to estimate associations between healthy behaviors (not smoking, at recommended body mass index [BMI], physical activity, healthy diet, and moderate to no alcohol intake) and outcomes (all-cause death, major coronary events, ischemic stroke, and heart failure events). All recommended lifestyle behaviors were significantly associated with lower risks of death, regardless of eGFR. Not smoking (versus current) and any moderate to vigorous physical activity (versus none) was significantly associated with reduced risks of major coronary and heart failure events, regardless of eGFR. Any (versus no) moderate or vigorous physical activity significantly associated with decreased risk of ischemic stroke events only among those with eGFR ≥60. Moderate to no daily alcohol intake (versus excessive) was significantly associated with an increased risk of major coronary events, regardless of eGFR. For heart failure events, a BMI of 18.5 to 30 associated with decreased risk, regardless of eGFR. Across all eGFR categories, the magnitude of risk reduction for death and all cardiovascular outcomes increased with greater numbers of recommended lifestyle behaviors. Recommended lifestyle behaviors are associated with lower risk of death and cardiovascular disease events among individuals with or without reduced kidney function, supporting lifestyle behaviors as potentially modifiable risk factors for people with kidney disease.

Looking for ischemia in patients with stable atypical chest pain: useful or useless?

Abstract Introduction Patients with stable atypical chest pain (SACP) represent more than half of those with chest pain who require an outpatient evaluation. It's not clear if in these patients the prognosis is linked more to the optimal control of risk factors and to the research and treatment of any unfavorable anatomical alterations (common trunk obstruction, proximal involvement of VAT, multivessel disease with systolic dysfunction of the left ventricle) rather than to ischemia assessment with functional tests. Methods In the past 20 years we have evaluated the lifestyles of 40,422 outpatient patients. 9% (3,638) had a history of stable chest pain with no history of previous cardiovascular events. In the 1,322 patients (36%) with non-anginal chest pain, no diagnostic examination was performed after the electrocardiogram (ECG) and the echocardiogram. 462 patients (13%) had typical chest pain, and 422 of them performed a coronary angiography. The other 1,854 (51%) patients with SACP underwent functional testing for ischemia (exercise ECG, ecostress, nuclear stress testing). They were also stratified according to the presence of 4 main modifiable lifestyles (cigarette smoking, diet, physical activity, obesity) and the 3 main cardiovascular risk factors (hypercholesterolemia, hypertension, diabetes). Results In the SACP group, the search for ischemia was positive in 192 patients (10.4%); 178 of them underwent coronary angiography, which demonstrated the presence of lesions with indication to revascularization to improve the prognosis, according to the ESC 2018 guidelines (Class IA), in 21 patients (11.7%). In the remaining 1,662 patients functional tests were negative. We performed one-year follow-up. Major coronary events (fatal and non-fatal infarction, sudden death) occurred in 22 patients (1.3%) with negative stress tests and at least 3 risk factors or bad lifestyles (especially smoking, diabetes, high LDL). In patients with positive stress tests, there were 3 events, (1.5%), that occurred among patients with at least 3 risk factors, too. No events occurred in patients with fewer than 3 risk factors or lifestyles in either group. Conclusions In patients with SACP and negative functional test the risk of major coronary events remains 1.3% at 1 year of follow-up; the events occurr in patients with 3 or more factors or lifestyle at risk (especially smoking, diabetes, elevated LDL). The prognosis is similar to those with positive ischemia research. The improvement of the outcomes should be entrusted more to a close control of the risk factors, to an optimal improvement of the lifestyles and to an anatomical evaluation (coronary CT) for the evaluation of those lesions that improve the prognosis rather than the search for ischemia which appears futile from a diagnostic and prognostic point of view as well as a source of economic waste. Funding Acknowledgement Type of funding source: None

Radiation-induced risk of ischemic heart disease following breast cancer radiotherapy in Denmark, 1977–2005

Background and purposeThe increase in the risk of heart disease from incidental exposure of the heart during radiotherapy for breast cancer has been estimated previously from retrospective data in Danish and Swedish women. Here we present an analysis of the Danish material updated with new cases and controls, extended follow-up period, and with refined dose estimates using simulator films or CT data. Material and methodsFrom the database of the Danish Breast Cancer Cooperative Group, we identified 531 women diagnosed with early-stage breast cancer from 1977 to 2005, who developed subsequent ischemic heart disease (cases) and matched them to 1069 controls without heart disease after radiotherapy. Data were available for precise dose estimation for 196 cases and 413 controls receiving tangential photon techniques. ResultsThe median of the mean heart doses for the women receiving tangential radiotherapy was 2.41 Gy for left- and 0.68 Gy for right-sided radiotherapy. The mean heart dose was higher for cases than controls (0.84 Gy and 0.71 Gy, respectively; p < 0.001). In this group, the linear increase in the excess odds ratio of major coronary events per gray of mean heart dose (K) was 19 percent (95% Confidence Interval(CI) 1% to 63%, p = 0.02). For patients treated with electron techniques, there was no significant association between mean heart dose and the risk of major coronary events (K = −0.05, 95% CI −12% to 9%, p = 1.00). ConclusionThe increase in the excess odds of major coronary events per gray mean heart dose using individual dose estimates is higher than previously reported.

Deep inspiration breath-hold radiotherapy for left-sided breast cancer after conserving surgery: A dose reduction for organs at risk

Background/Aim. For patients with left-sided breast cancer, a major concern is the dose of radiation delivered to the heart, because of increased risk of exposure and consequently increased risk of major coronary events and side effects. In order to reduce the dose to the heart during breast irradiation, deep inspiration breath-hold (DIBH) technique was implemented in our institution. The aim of this retrospective study was to compare dosimetric parameters of DIBH on the heart, left anterior descending artery (LAD) and ipsilateral lung (IL), compared with free breathing (FB) technique. Methods. Twenty patients who underwent radiotherapy with DIBH at our institution were retrospectively analyzed. Two computed tomography (CT) scans were acquired for each patient, FB-CT and DIBH-CT. Plans consisted of two opposed tangential segmented beams and one direct beam with small dose contribution. Doses to the heart, LAD, and IL were assessed. Results. Dosimetric comparison between FB and DIBH for mean dose to the heart was 5.17 Gy vs. 3.68 Gy, respectively (p &lt; 0.0001), and the mean percentage of the volume receiving 25 Gy was 4.63% vs. 0.85%, respectively (p &lt; 0.0001). Mean dose for LAD was 26.09 Gy vs. 11.89 Gy, respectively (p = 0.00014). Mean percentage of the volume receiving 20 Gy for the IL was 15.16% vs. 13.26% (p = 0.0007) for FB and DIBH, respectively. Conclusion. Implementation of DIBH technique in radiotherapy treatment of patients with left-sided breast cancer statistically significantly reduces the dose delivered to the surrounding organs at risk, particularly to the heart and LAD, with optimal target coverage.