Baseline Coronary Heart Disease Research Articles

Trends in cardiovascular health metrics and associations with long-term mortality among US adults with coronary heart disease

Background and aimsOur study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US. Methods and resultsThe cohort study was conducted based on the National Health and Nutrition Examination Survey 1999–2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively. ConclusionSubstantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them.

Cardiac radiation dose is associated with inferior survival but not cardiac events in patients with locally advanced non-small cell lung cancer in the era of immune checkpoint inhibitor consolidation

PurposeWe assessed the association of cardiac radiation dose with cardiac events and survival post-chemoradiation therapy (CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) after adoption of modern radiation therapy (RT) techniques, stricter cardiac dose constraints, and immune checkpoint inhibitor (ICI) consolidation. Methods and MaterialsThis single-institution, multi-site retrospective study included 335 patients with LA-NSCLC treated with definitive, concurrent CRT between October 2017 and December 2021. All patients were evaluated for ICI consolidation. Planning dose constraints included heart mean dose < 20 Gy (<10 Gy if feasible) and heart volume receiving ≥ 50 Gy (V50Gy) < 25 %. Twenty-one dosimetric parameters for three different cardiac structures (heart, left anterior descending coronary artery [LAD], and left ventricle) were extracted. Primary endpoint was any major adverse cardiac event (MACE) post-CRT, defined as acute coronary syndrome, heart failure, coronary revascularization, or cardiac-related death. Secondary endpoints were: grade ≥ 3 cardiac events (per CTCAE v5.0), overall survival (OS), lung cancer-specific mortality (LCSM), and other-cause mortality (OCM). ResultsMedian age was 68 years, 139 (41 %) had baseline coronary heart disease, and 225 (67 %) received ICI consolidation. Proton therapy was used in 117 (35 %) and intensity-modulated RT in 199 (59 %). Median LAD V15Gy was 1.4 % (IQR 0–22) and median heart mean dose was 8.7 Gy (IQR 4.6–14.4). Median follow-up was 3.3 years. Two-year cumulative incidence of MACE was 9.5 % for all patients and 14.3 % for those with baseline coronary heart disease. Two-year cumulative incidence of grade ≥ 3 cardiac events was 20.4 %. No cardiac dosimetric parameter was associated with an increased risk of MACE or grade ≥ 3 cardiac events. On multivariable analysis, cardiac dose (LAD V15Gy and heart mean dose) was associated with worse OS, driven by an association with LCSM but not OCM. ConclusionsWith modern RT techniques, stricter cardiac dose constraints, and ICI consolidation, cardiac dose was associated with LCSM but not OCM or cardiac events in patients with LA-NSCLC.

Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease

Background and aimsDespite interest in the use of polygenic risk scores (PRS) for predicting coronary heart disease (CHD) risk, the clinical utility of PRS compared to conventional risk factors has not been demonstrated. We compared the performance of PRS with that of high-sensitivity C-reactive protein (hsCRP) in two well-established cohorts. MethodsThe study population included individuals of European ancestry free of baseline CHD from ARIC (N = 13,113) and the Framingham Offspring Study (FHS) (N = 2,696). The primary predictors included a validated PRS consisting of >6.6 million single nucleotide polymorphisms and hsCRP. The outcome was incident CHD, defined as non-fatal or fatal myocardial infarction. We compared the performance of both predictors after adjusting for the Pooled Cohort Equations in multivariable-adjusted Cox regression models. We assessed discrimination and reclassification using c-statistics and net reclassification improvement. ResultsIncident CHD occurred in 565 ARIC and 153 FHS participants. In multivariable-adjusted models, both PRS and hsCRP were associated with incident CHD (p < 0.05 in both cohorts). In models incorporating both predictors, strengths of association were similar. For instance, in ARIC, the hazard ratio per SD increment was 1.38 (95% CI, 1.27–1.50, p = 2.94 × 10−14) for PRS and 1.41 (1.30–1.55, p = 3.10 × 10−15) for hsCRP. Neither predictor significantly increased model discrimination or net reclassification when compared with models containing the Pooled Cohort Equations alone. ConclusionsIn two independent cohorts, PRS performed similarly to hsCRP for the prediction of CHD risk. These findings suggest PRS does not have unique clinical utility beyond this widely-available, inexpensive measure of risk in unselected middle-aged populations.

Heart rate variability and the risk of heart failure and its subtypes in post-menopausal women: The Women's Health Initiative study.

BackgroundLow heart rate variability (HRV), a measure of autonomic imbalance, is associated with increased risk of coronary heart disease (CHD) and heart failure (HF). However, its relationship with HF subtypes; heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) has not been studied prior.Methods and findingsWe conducted a longitudinal study in Women’s Health Initiative study cohort to investigate the association of baseline quartiles of resting heart rate (rHR) and HRV measures; SDNN (SD of normal-to-normal RR interval) and RMSSD (root mean square of successive difference of RR interval) measured by twelve-lead electrocardiogram (ECG) on enrollment, with the risk of hospitalized HF and its subtypes. Total of 28,603 post-menopausal women, predominantly non-Hispanic whites (69%), with a mean (SD) age of 62.6 (7.1) years, free of baseline CHD and HF were included. In a fully adjusted cox-proportional hazards regression model which adjusted for age, race, BMI, alcohol intake, education, physical activity, hyperlipidemia, hypertension, left ventricular hypertrophy, use of beta-blocker, calcium-channel blocker, hormone therapy, and time-varying incident CHD, the hazard ratios of lowest quartile of HRV (Q1) with HF risk were significant (Q1 SDNN compared to Q4 SDNN: 1.22, 95% CI 1.07, 1.39; Q1 RMSSD compared to Q4 RMSSD: 1.17, 95% CI 1.02, 1.33). On subgroup analysis of HF subtypes, low HRV was associated with elevated HFpEF risk (Q1 vs Q4 SDNN: 1.22, 95% CI 1.02, 1.47) but not with HFrEF (Q1 vs Q4 SDNN: 1.19, 95% CI 0.95, 1.50; Q1 RMSSD: 1.13, 95% CI 0.90, 1.43).ConclusionLow HRV is associated with elevated overall hospitalized HF risk and HFpEF risk in post-menopausal women. Whether interventions to increase HRV through healthy lifestyle changes will decrease HF risk warrants further investigation.

Depressive Symptoms and Incident Hospitalization for Heart Failure: Findings From the REGARDS Study.

BackgroundDepressive symptoms are risk factors for several forms of cardiovascular disease including coronary heart disease (CHD). However, it is unclear whether depressive symptoms are associated with incident heart failure (HF), including hospitalization for HF overall or by subtype: HF with preserved (HFpEF) or reduced ejection fraction (HFrEF).Methods and ResultsAmong 26 268 HF‐free participants in the REGARDS (Reasons for Geographic And Racial Differences in Stroke) study, a prospective biracial cohort of US community‐dwelling adults ≥45 years, baseline depressive symptoms were defined as a score ≥4 on the 4‐item Center for Epidemiologic Studies Depression scale. Incident HF hospitalizations were expert‐adjudicated and categorized as HFpEF (EF ≥50%) and HFrEF, including mid‐range EF (EF<50%). Over a median of 9.2 [IQR 6.2–10.9] years of follow‐up, there were 872 incident HF hospitalizations, 526 among those without CHD and 334 among those with CHD. The age‐adjusted HF hospitalization incidence rates per 1000 person‐years were 4.9 (95% CI 4.0–5.9) for participants with depressive symptoms versus 3.2 (95% CI 3.0–3.5) for those without depressive symptoms (P<0.001). For overall HF, the elevated risk became attenuated after controlling for covariates. When HFpEF was assessed separately, depressive symptoms were associated with incident hospitalization after controlling for all covariates (hazard ratio [HR] 1.48, 95% CI 1.00–2.18) among those without baseline CHD. In contrast, depressive symptoms were not associated with incident HFrEF hospitalizations.ConclusionsAmong individuals free of CHD at baseline, depressive symptoms were associated with incident hospitalization for HFpEF, but not for HFrEF, or among those with baseline CHD.

Abstract P216: Association Of Heart Rate Variability With The Risk Of Heart Failure And Its Sub-types In Post-menopausal Women: A Longitudinal Cohort Study

Background: Previously our research findings revealed that low heart rate variability, a measure of autonomic imbalance, is associated with increased incidence of coronary heart disease (CHD) and heart failure (HF) in a cohort of post-menopausal women. Since CHD is strongly associated with HF, we investigated the effect of CHD on relationship of HRV and HF subtypes, i.e., heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), in post-menopausal women. Methods: Total of 28,603 post-menopausal women free of baseline CHD, HF and cardiac arrhythmias enrolled in Women’s Health Initiative (WHI) study, were followed for incident hospitalized CHD, HF and its subtypes (HFrEF vs HFpEF). Using multivariate cox proportional hazard model, we estimated the association of above outcomes with baseline quartiles of HRV measures; SDNN (standard deviation of normal-to-normal RR interval) and RMSSD (root mean square of successive difference of RR interval) produced by 10-second twelve-lead ECG on enrollment. We then evaluated the relationship between HRV and HF subtypes stratified by incident CHD. Results: A total of 2279 incident CHD and 1562 incident HF events occurred during a median follow-up duration of 17.5 years. After adjusting for incident CHD in a multivariate cox proportional model, association of low SDNN and RMSSD with incident HF remained significant (SDNN HR 1.19, CI 1.05 - 1.35; RMSSD HR 1.13 (1.00 - 1.29). However, in stratified analysis low SDNN was associated with increased incidence of HFpEF only among participants without incident CHD (HR 1.29, CI 1.05 - 1.58) and not in those with incident CHD (HR 1.06, CI 0.77 - 1.47). Whereas low SDNN was associated with increased incidence of HFrEF only among participants with incident CHD (HR 1.44. CI 1.05 - 1.98) and not in those without incident CHD (HR 1.18, CI 0.87 - 1.61). Conclusion: Post-menopausal women with low HRV who develop CHD have an increased risk of HFrEF while those who don’t develop CHD have an increased risk of HFpEF. The relationship between autonomic imbalance and HF subtypes is dependent on CHD status.

Critical Volumetric Threshold of 15 Gy Exposure to Left Coronary Arteries Predicts Major Adverse Cardiac Events and Mortality in Lung Cancer Radiotherapy

<h3>Purpose/Objective(s)</h3> Left anterior descending (LAD) coronary artery volume receiving 15 Gy (V15 Gy) ≥10% and left circumflex (LCX) V15 Gy ≥14% are associated with an increased risk of major adverse cardiac events (MACE), while LAD V15 Gy ≥10% can significantly increase the risk of mortality in patients with non-small cell lung cancer (NSCLC). Given that reduction of coronary dose is a modifiable risk factor during RT planning, we identified absolute critical volume (vol) thresholds of left coronary artery (LCA) exposure to 15 Gy that predict for MACE and all-cause mortality (ACM). <h3>Materials/Methods</h3> Retrospective analysis of 701 patients with locally advanced NSCLC treated with RT between 2003 and 2014. Coronary arteries were manually segmented with an 8-mm brush size. The absolute vol (cc) of LAD, LCX, or LCA (combined LAD+LCX) structures receiving ≥15 Gy were calculated. Area under the receiver operating curve (AUC) and cut-point analyses estimating MACE (unstable angina, heart failure, myocardial infarction, coronary revascularization, and cardiac death) were performed. Fine and Gray and Cox regressions were performed, adjusting for pre-existing coronary heart disease (CHD) and other cardiovascular and cancer prognostics factors. <h3>Results</h3> The median age was 65 years (interquartile range, 57-73 years) and 50.8% (n = 356) were men. The optimal cut-point (C-index) for the absolute vol. receiving ≥15 Gy for the LAD, LCX, and LCA was ≥1.1 cc (0.63), ≥1.3 cc (0.65), and ≥2.6 cc (0.64), respectively. Adjusting for baseline CHD and other factors, there was an increased risk of MACE with an LAD V15 Gy vol. ≥1.1 cc (adjusted hazard ratio [AHR], 7.59; 95% confidence interval [CI], 2.24-25.69; P = 0.001), an LCX V15 Gy vol. ≥1.3 cc (AHR, 8.24; 95% CI, 2.84-23.90; P < 0.001), and an LCA V15 Gy vol. ≥2.6 cc (AHR, 9.01; 95% CI, 2.66-30.56; P < 0.001), while only LAD-containing variables (not LCX alone) were associated with an increased risk of ACM as follows; LAD V15 Gy vol. ≥1.1 cc (AHR, 1.44; 95% CI, 1.14-1.81; P = 0.002) and LCA V15 Gy vol. ≥2.6 cc (AHR, 1.31; 95% CI, 1.04-1.64; P = 0.023). There was a significantly increased risk of all-cause mortality in CHD-negative patients with an LAD V15 Gy vol. ≥1.1 (HR, 1.39; 95% CI, 1.10-1.74; P = 0.005) and LCA V15 Gy vol. ≥2.6 (HR, 1.32; 95% CI, 1.05-1.65; P = 0.019); but not among CHD-positive patients, (P > 0.05). Specifically, the 2-year ACM estimates in CHD-negative patients for LAD V15 Gy vol. (≥1.1 vs. < 1.1 cc) was 50.9% vs. 42.3%, and for LCA V15 Gy vol. (≥2.6 vs. < 2.6 cc) was 51.1% vs. 43.0%, respectively (P for interaction ≤.01). <h3>Conclusion</h3> Critical volume thresholds of 15 Gy for the LAD and LCA were independent predictors of MACE and ACM, particularly in patients without CHD. These constraints may help inform RT planning by guiding LCA dose reduction and identify patients who may benefit most from advanced RT techniques to mitigate excess cardiac risk.

Association of Clonal Hematopoiesis With Incident Heart Failure

BackgroundAge-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF). ObjectivesThis study sought to evaluate whether CHIP is associated with incident HF. MethodsCHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses. ResultsOf 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction. ConclusionsCHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.

Decrease of coronary heart disease risk with GLP1-receptor agonists or SGLT2 inhibitors therapy in patients with type 2 diabetes in primary cardiovascular prevention: A 24 months follow-up study

AimsThe aim of this real-world study is to evaluate the effect of glucagon-like peptide1 receptor-agonist (GLP1 RA) and sodium-glucose co-transporter2 inhibitor (SGLT2i) on coronary heart disease (CHD) risk, in patients with type 2 diabetes (T2D) in primary cardiovascular prevention. MethodsData from 312 patients with T2D, without CHD history, starting treatment with GLP1 RA (n = 174) or SGLT2i (n = 138), were retrospectively collected. UKPDS-RE score was used to estimate 10-years risk for CHD before and 6, 12 and 24 months after prescription. ResultsThe 10-year CHD risk significantly decreased over 24 months in both GLP1 RA and SGLT2i groups (p = 0.037 and p < 0.001, respectively), with 3% and 7% CHD risk reduction already obtained after the first 6 months of GLP1 RA and SGLT2i therapy respectively (p < 0.001 in both groups. Analyses by categories of baseline CHD risk showed significant reductions of CHD risk in the severe risk categories of both groups (p < 0.001). CHD risk reduction obtained with SGLT2i was higher than with GLP1 RA at 6 and 12 months but not at 24 months. ConclusionThis real-world study shows that both GLP1 RA and SGLT2i reduce the 10-year risk for cardiovascular disease in patients with T2D in primary cardiovascular prevention.

Association of Left Anterior Descending Coronary Artery Radiation Dose With Major Adverse Cardiac Events and Mortality in Patients With Non–Small Cell Lung Cancer

Radiotherapy accelerates coronary heart disease (CHD), but the dose to critical cardiac substructures has not been systematically studied in lung cancer. To examine independent cardiac substructure radiotherapy factors for major adverse cardiac events (MACE) and all-cause mortality in patients with locally advanced non-small cell lung cancer (NSCLC). A retrospective cohort analysis of 701 patients with locally advanced NSCLC treated with thoracic radiotherapy at Harvard University-affiliated hospitals between December 1, 2003, and January 27, 2014, was performed. Data analysis was conducted between January 12, 2019, and July 22, 2020. Cardiac substructures were manually delineated. Radiotherapy dose parameters (mean, maximum, and the volume [V, percentage] receiving a specific Gray [Gy] dose in 5-Gy increments) were calculated. Receiver operating curve and cut-point analyses estimating MACE (unstable angina, heart failure hospitalization or urgent visit, myocardial infarction, coronary revascularization, and cardiac death) were performed. Fine and Gray and Cox regressions were adjusted for preexisting CHD and other prognostic factors. MACE and all-cause mortality. Of the 701 patients included in the analysis, 356 were men (50.8%). The median age was 65 years (interquartile range, 57-73 years). The optimal cut points for substructure and radiotherapy doses (highest C-index value) were left anterior descending (LAD) coronary artery V15 Gy greater than or equal to 10% (0.64), left circumflex coronary artery V15 Gy greater than or equal to 14% (0.64), left ventricle V15 Gy greater than or equal to 1% (0.64), and mean total coronary artery dose greater than or equal to 7 Gy (0.62). Adjusting for baseline CHD status and other prognostic factors, an LAD coronary artery V15 Gy greater than or equal to 10% was associated with increased risk of MACE (adjusted hazard ratio, 13.90; 95% CI, 1.23-157.21; P = .03) and all-cause mortality (adjusted hazard ratio, 1.58; 95% CI, 1.09-2.29; P = .02). Among patients without CHD, associations with increased 1-year MACE were noted for LAD coronary artery V15 Gy greater than or equal to 10% (4.9% vs 0%), left circumflex coronary artery V15 Gy greater than or equal to 14% (5.2% vs 0.7%), left ventricle V15 Gy greater than or equal to 1% (5.0% vs 0.4%), and mean total coronary artery dose greater than or equal to 7 Gy (4.8% vs 0%) (all P ≤ .001), but only a left ventricle V15 Gy greater than or equal to 1% increased the risk among patients with CHD (8.4% vs 4.1%; P = .046). Among patients without CHD, 2-year all-cause mortality was increased with an LAD coronary artery V15 Gy greater than or equal to 10% (51.2% vs 42.2%; P = .009) and mean total coronary artery dose greater than or equal to 7 Gy (53.2% vs 40.0%; P = .01). The findings of this cohort study suggest that optimal cardiac dose constraints may differ based on preexisting CHD. Although the LAD coronary artery V15 Gy greater than or equal to 10% appeared to be an independent estimator of the probability of MACE and all-cause mortality, particularly in patients without CHD, left ventricle V15 Gy greater than or equal to 1% appeared to confer an increased risk of MACE among patients with CHD. These constraints are worthy of further study because there is a need for improved cardiac risk stratification and aggressive risk mitigation strategies.

Abstract 16122: Comparative Risk of Incident Coronary Heart Disease Across Multiple Chronic Inflammatory Diseases

Introduction: Inflammation plays an important role in the pathogenesis of coronary heart disease (CHD). Chronic inflammatory diseases (CIDs) may serve as models to provide insights into the relationships between immune dysfunction, inflammation, and CHD. To investigate this further, we analyzed the risk of incident CHD across different CIDs. Methods: We created a cohort of individuals with CIDs and non-CID controls (frequency-matched on demographics and CHD risk factors), free of baseline CHD, receiving regular outpatient care in a large medical system from 2000 to 2019. CIDs included psoriasis, rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and inflammatory bowel disease (IBD). CHD was defined as myocardial infarction (MI), angina, or coronary revascularization. We used adjusted hazards models to determine incident CHD risk for each CID relative to controls. We also analyzed incident CHD risk by severity of inflammation (baseline C-reactive protein) or immune dysfunction (baseline CD4 T cell level in HIV). Results: Of 18,129 individuals with CIDs and 18,988 controls, there were 1,011 incident CHD events over a median of 3.5 years. After adjusting for demographics and CHD risk factors, CHD risk was significantly elevated in SLE [hazard ratio (HR) 2.85, 95% confidence interval (CI) 2.19-3.71, p&lt;0.01], SSc (HR 2.14, 95% CI 1.54-2.99, p&lt;0.01), HIV (HR 1.38, 95% CI 1.12-1.69, p&lt;0.01), and RA (HR 1.22, 95% CI 1.00-1.49, p=0.05). Findings were similar with MI as the lone outcome. When CIDs were categorized by inflammation or immune dysfunction, there was a pattern of higher CHD risk with higher levels of inflammation/immune dysfunction across CIDs (Figure). Conclusions: Our results show that SLE, SSc, HIV, and RA were associated with significantly elevated risks of incident CHD and MI. Higher levels of inflammation or immune dysfunction were associated with heightened CHD risk within CIDs.

Abstract 15273: Estimating Coronary Heart Disease Risk and Treatment Benefit in Patients With Familial Hypercholesterolemia to Enable Shared Decision Making

Introduction: Current risk equations for coronary heart disease (CHD) do not take into account family history or cumulative exposure to LDL-C. We modified CHD risk equations for use in familial hypercholesterolemia (FH) patients and developed a decision aid (DA) for FH to facilitate shared decision making (SDM). Methods: Literature review, evidence synthesis and expert input were used to adapt the 30-year Framingham Risk Score (FRS) and 10-year ACC/AHA pooled cohort equations to calculate the CHD risk in individuals with FH aged 20-39 years and ≥40 years, respectively. Based on published data, estimated risk was multiplied by 2 for family history of early CHD or 3 in the presence of a pathogenic variant. Treatment benefit of lipid lowering was estimated based on the ‘cumulative exposure to LDL-C’ model ( JACC 2012; 60 ) using the following equations: Post-treatment 30-yr risk in those aged 20-39 years = Baseline Risk (FRS) x 0.54 delta LDL-C (mmol/L) Post-treatment 10-yr risk in those aged ≥40 years = Baseline Risk (ACC/AHA Pooled Cohort) x 0.72 delta LDL-C (mmol/L) To convey CHD risk and treatment benefit, we developed a DA using an iterative, patient-centered design process for use in FH encounters. Results: Using the DA, providers can discuss baseline CHD risk estimates, lipid lowering drug (LLD) options and the expected post-treatment risk reduction with FH patients. The estimated % LDL-C reduction for each LLD and the predicted risk reduction per mmol/L of LDL-C lowered were obtained from literature review. Lowering LDL-C by 1 mmol/L (39 mg/dL) was associated with a 28% CHD risk reduction over 10 years and a 46% reduction over 30 years ( Eur Heart J 2017; 38 ). We describe 2 examples of estimating CHD risk and treatment benefit in FH cases in Table 1 . Conclusion: We adapted CHD risk prediction equations to account for family history of CHD and presence of a pathogenic FH variant and designed a DA to convey personalized CHD risk estimates and treatment benefit to facilitate SDM with FH patients.

Net Clinical Benefit of Low Dose Rivaroxaban in Coronary Heart Disease: A Systematic Review and Meta-Analysis

Introduction US Food and Drug Administration has recently approved the use of rivaroxaban 2.5mg BID in patients with coronary heart disease based on Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. However, it's unclear whether there is net clinical benefit with use of rivaroxaban in such patients. Therefore, we did a systematic review and meta-analysis to evaluate the effects of rivaroxaban on clinical outcomes in coronary heart disease patients. Methods: Embase, Ovid, Pubmed and Scopus were extensively searched from inception of these databases to April 2019 by two independent reviewers. Only randomized controlled trials of low dose rivaroxaban (2.5 mg BID) reporting mortality and cardiovascular outcomes of interest in baseline coronary heart disease patients (≥ 18 years) with at least 1000 patients and follow-up of ≥ 1 year were included. The co-primary outcomes were cardiovascular mortality and all-cause mortality. The secondary endpoints were myocardial infarction (MI), stroke, major adverse cardiovascular events, major bleeding and cerebral nervous system (CNS) bleeding. Cochrane Collaboration's tool was used for risk of bias assessment. Statistical heterogeneity was quantified using I2 statistics whereas publication bias was assessed with Eggers regression test. We combined estimates using DerSimonian and Laird random effects models. Outcomes were reported as hazard ratios (HR) with 95% confidence intervals (CI). Results: Five randomized control trials including 39,979 patients were included in our meta-analysis. Trials ATLAS and Commander HF used placebo as their control while COMPASS and GEMINI ACS-1 used aspirin as control. Pioneer AF-PCI used vitamin K antagonist as the control. Mean age (SD) of the patients was 65.6 ± 3.7 years with 74.3% females. Mean follow up in years was 1.6 ±0.5. Majority of the patients in each trial had hypertension. Our pooled analysis showed reduction in all-cause mortality (HR, 0.85, 95% CI, 0.72-1.00, P=0.05), cardiovascular mortality (HR, 0.83, 95% CI, 0.70-1.00, P=0.05), MI (HR, 0.88, 95% CI, 0.78-1.00, P=0.05) and stroke (HR, 0.70, 95% CI, 0.53-0.94, P=0.02) with low dose rivaroxaban. No significant difference in risk of bleeding was observed (HR, 1.45, 95% CI, 0.83-2.51, P=0.19). Our pooled analysis also showed reduction in major cardiovascular events (HR, 0.91, 95% CI, 0.85-0.98, P=0.01). CNS bleeding was only reported by ATLAS and COMPASS trials and net effect showed no statistically significant bleeding risk (HR, 1.63, 95% CI, 0.70-3.79, P=0.26). Conclusion: Our data suggest that the use of rivaroxaban is associated with reduction in all-cause and cardiovascular mortality in coronary heart disease patients without significantly increasing the risk of bleeding. To further decrease the residual risk of cardiovascular events in coronary heart disease patients, low dose rivaroxaban can be considered by clinicians. Disclosures No relevant conflicts of interest to declare.

Dietary Patterns and Incident Heart Failure in U.S. Adults Without Known Coronary Disease

BackgroundDietary patterns and associations with incident heart failure (HF) are not well established in the United States. ObjectivesThe purpose of this study was to determine associations of 5 dietary patterns with incident HF hospitalizations among U.S. adults. MethodsThe REGARDS (REasons for Geographic and Racial Differences in Stroke) trial is a prospective cohort of black and white adults followed from 2003 to 2007 through 2014. Inclusion criteria included completion of a food frequency questionnaire and no baseline coronary heart disease or HF. Five dietary patterns (convenience, plant-based, sweets, Southern, and alcohol/salads) were derived from principal component analysis. The primary endpoint was incident HF hospitalization. ResultsThis study included 16,068 participants (mean age 64.0 ± 9.1 years, 58.7% women, 33.6% black participants, 34.0% residents of the stroke belt). After a median of 8.7 years of follow-up, 363 participants had incident HF hospitalizations. Compared with the lowest quartile, the highest quartile of adherence to the plant-based dietary pattern was associated with a 41% lower risk of HF in multivariable-adjusted models (hazard ratio: 0.59; 95% confidence interval: 0.41 to 0.86; p = 0.004). Highest adherence to the Southern dietary pattern was associated with a 72% higher risk of HF after adjusting for age, sex, and race and for other potential confounders (education, income, region of residence, total energy intake, smoking, physical activity, and sodium intake; hazard ratio: 1.72; 95% confidence interval: 1.20 to 2.46; p = 0.005). However, the association was attenuated and no longer statistically significant after further adjusting for body mass index in kg/m2, waist circumference, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and chronic kidney disease. No statistically significant associations were observed with incident HF with reduced or preserved ejection fraction hospitalizations and the dietary patterns. No associations were observed with the other 3 dietary patterns. ConclusionsAdherence to a plant-based dietary pattern was inversely associated with incident HF risk, whereas the Southern dietary pattern was positively associated with incident HF risk.

Cardiac Events after Radiation Therapy (RT) for Stage II-III Non-Small Cell Lung Cancer (NSCLC): Analysis of 748 Patients

Radiation therapy-associated cardiac toxicity in patients with NSCLC arises sooner and is of greater clinical significance than historically appreciated. Recent studies have been limited by inconsistent definitions and small size. This study reports major cardiac events after RT in a large cohort of patients with NSCLC using comprehensive, validated cardiac toxicity criteria and dose-volume data. Retrospective study of 748 patients with Stage II (9%) to III (91%) NSCLC treated with 3D-conformal (77%) or intensity-modulated (22%) RT (median dose, 64 Gy) and chemotherapy (61%), chemotherapy and surgery (33%), or RT alone (4%) between 1998–2014 at one institution. Hearts were re-contoured per cardiac atlas definitions. Patients without baseline coronary heart disease (CHD) or CHD risk equivalent were stratified by Framingham risk. Primary endpoint was major cardiac events, defined as any grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, v4.03) or Major Adverse Cardiac Events (MACE). Estimates of Kaplan-Meier overall survival (OS) and cumulative incidence of cardiac events (non-cardiac death as a competing risk) were calculated. Fine and Gray and Cox regressions were performed. Median follow up from RT was 1.9 years. Median mean heart dose was 12.3 Gy. Two-year OS stratified by low, moderate, or high Framingham risk group or known CHD was 62.7%, 56.0%, 47.0%, and 46.8%, respectively (P=.001). Median time to first major cardiac event was 10.4 months; cumulative incidence at 1, 2, and 5-years was 18.2%, 23.5%, and 32.4%, respectively. Two-year cumulative incidence of major cardiac events (conduction, 12.0%; heart failure, 5.7%; MACE, 4.8%; pericardial [all], 4.7%; pericardial [effusion, cytology benign], 1.8%; coronary/ischemic, 2.5%; valvular, 1.1%; and cardiopulmonary/other, 5.4%) was increased in patients with vs without baseline CHD (31.2% vs 18.9%; P<.0001) and those with mean heart dose >12 Gy vs ≤12 Gy (26.7% vs 19.3%; P=.009), respectively. On multivariable analysis (MVA), baseline CHD (hazard ratio [HR] 1.75, 95% CI 1.35–2.28; P<.0001) and mean heart dose (HR 1.09/5 Gy, 95% CI 1.02–1.16; P=.013) were significantly associated with major cardiac events. On MVA accounting for baseline CHD and known lung cancer prognostic factors, major cardiac events were significantly associated with decreased OS (HR 2.91, 95% CI 2.39–3.55; P<.0001), while mean heart dose was not (HR 1.04/5 Gy, 95% CI 0.99–1.09; P=.107). In this large cohort of patients with NSCLC, major cardiac events were common, occurred sooner than previously reported, and were associated with baseline CHD and heart dose. These results build upon recent reports, support efforts to minimize heart irradiation, and highlight the importance of pre-treatment cardiac risk assessment and development of risk mitigation strategies for high risk patients.

Abstract 546: Metformin Significantly Increased Survival Rate in Patients With Diabetes and Comorbid Heart Disease

Objective: We assessed the hypothesis that metformin use significantly decreases risk of all-cause and heart disease (HD) mortality in patients with diabetes mellitus (DM). Methods: Subjects with DM aged ≥30 (n=3612) participating in 1999 -2010 National Health and Nutrition Examination Surveys, who had anti-DM drug therapy information, and were followed up by December 2011 were analyzed. Baseline DM, coronary heart disease (CHD) and heart failure (HF) were defined as a physician-diagnosis of the disease(s). Death from HD was classified using ICD10:I20-I25). Results: Mean (SD) age of 3612 participants was 63.1 (13.02), 83.4% (3056/3612) were under anti-DM therapies, and 20.3% was in metformin monotherapy, 4.9% in metformin combination (MCO), 24.8% in insulin, 45.4% in thiazolidinedione, sulfonylurea, and combinations, and 4.7% in any other antidiabetic drugs therapies. Baseline CHD and HF rates were 11.38% and 9.13%. At the end of follow-up, 1024 died from all-cause (21.86%), and 222 died from HD. Multivariate Cox’s proportional hazard regression analysis indicated that diabetic patients with comorbid HD (CHD and/or HF) had significant higher all-cause mortality than those without. However, these excess mortalities were significantly reduced in patients with metformin therapies than their counterparts without metformin. The hazard ratios (HR, 95%CI) of metformin use versus those without for all-cause mortality was 0.53 (0.38-0.76, p=0.001). Diabetic patients with CHD and with metformin therapies had a significantly lower 10-year all-cause mortality than those without metformin (33% vs. 64%, p&lt;0.001). Similarly, diabetic patients with HF and with metformin therapies had a significantly lower 10-year all-cause mortality than their counterparts (42.8% vs. 73.1%, p&lt;0.001). The effects of metformin on all-cause mortality were positively modified after adjusting dyslipidemia and insulin resistance. In conclusion , metformin significantly increased survival rates from all-cause mortality in diabetic patients with comorbid CHD and/or HF. The mortality risk reduction may be partially explained by an effect of metformin on a reduction of dyslipidemia and insulin resistance.

A Retrospective Study to Examine Healthcare Costs Related to Cardiovascular Events in Individuals with Hyperlipidemia.

IntroductionFew studies have demonstrated the cost burden of cardiovascular events (CVEs) among patients with hyperlipidemia. The primary objective of this study was to determine the mean costs associated with CVEs among patients with hyperlipidemia by follow-up time period. Secondary objectives of this study included characterizing costs by CVE type and coronary heart disease (CHD) risk.MethodsThis retrospective cohort study used longitudinal claims to calculate payer costs according to CHD risk level and type of CVE, during several follow-up periods (acute and short-term, comprising year 1; plus years 2 and 3).ResultsThere were 193,385 patients with hyperlipidemia with a CVE. Costs in the acute (30-day) period were highest ($22,404) driven by inpatient care (77%). Costs remained high ($15,133 in year 3) with ambulatory care (from 14% in acute to 37% in year 3) and pharmaceutical costs (from 2% in acute to 24% in year 3) representing a greater proportion. After second and third CVEs, acute costs were lower than for the first CVE. But in the post-acute periods, costs were higher after second and third CVEs than after first CVEs. Acute costs varied considerably by type of CVE ($9149 for transient ischemic attack to $54,251 for coronary artery bypass graft; P < 0.001), but post-acute costs were more similar across types. Costs differed by baseline CHD risk for all follow-up periods (P < 0.001), but less than by CVE type. As expected, patients without CVEs had significantly lower costs.ConclusionAmong patients with hyperlipidemia, the economic burden of CVEs is substantial up to 3 years after a CVE. Costs remain high after subsequent CVEs and actually increase for non-inpatient utilization.FundingAmgen Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0264-7) contains supplementary material, which is available to authorized users.

Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT

Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.

The relation of ambulatory heart rate with all-cause mortality among middle-aged men: a prospective cohort study.

The aim of this study was to investigate the association between average 24-hour ambulatory heart rate and all-cause mortality, while adjusting for resting clinical heart rate, cardiorespiratory fitness, occupational and leisure time physical activity as well as classical risk factors. A group of 439 middle-aged male workers free of baseline coronary heart disease from the Belgian Physical Fitness Study was included in the analysis. Data were collected by questionnaires and clinical examinations from 1976 to 1978. All-cause mortality was collected from the national mortality registration with a mean follow-up period of 16.5 years, with a total of 48 events. After adjustment for all before mentioned confounders in a Cox proportional hazards regression analysis, a significant increased risk for all-cause mortality was found among the tertile of workers with highest average ambulatory heart rate compared to the tertile with lowest ambulatory heart rate (Hazard ratio = 3.21, 95% confidence interval: 1.22–8.44). No significant independent association was found between resting clinic heart rate and all-cause mortality. The study indicates that average 24-hour ambulatory heart rate is a strong predictor of all-cause mortality independent from resting clinic heart rate, cardiorespiratory fitness, occupational and leisure time physical activity and other classical risk factors among healthy middle-aged workers.

Abstract P080: The Combined Effect of Low Income and Low Education on Coronary Heart Disease Outcomes in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Background: Low income (LoINC) and low education (LoED) have both been associated with higher coronary heart disease (CHD) risk, but few studies have examined the combined effects of both LoINC and LoED. Hypothesis: The combination of LoINC and LoED is more strongly associated with incident CHD than either LoINC and LoED, or neither. Methods: REGARDS recruited 30,239 black and white participants aged &gt; 45 years residing in the 48 contiguous US between 2003-2007. Baseline data included telephone interviews and in-home visits, and follow-up was conducted every 6 months to detect potential events with expert adjudication of endpoints based on medical record review. Low income (LoInc) was defined as annual household income &lt;$35,000, and low education (LoEd) was defined as less than a high school education. Income and education were combined into four mutually exclusive exposure groups (noLoInc+noLoEd, noLoInc+LoEd, LoInc+noLoEd ,LoInc+LoEd, ). CHD outcomes were definite or probable myocardial infarction or acute CHD death. We constructed Cox models estimating the hazard ratios (HR) for CHD, sequentially adjusting for sociodemographics, health behaviors, physiologic parameters, access to healthcare, and stress and depression. Because of significant interaction by age (p&lt;0.001), analyses were stratified at age 65. Results: We analyzed 24,461 participants without baseline CHD, with numbers in each income/education group as shown in the Table. LoInc+LoEd was associated with the highest risk of CHD among those aged &lt; 65 years, but not among those &gt;65 years of age. LoEd was associated with higher CHD risk in those age &gt;65 years and LoInc was not, but LoInc was associated with higher CHD risk in those age &lt; 65 years, but LoEd was not. Conclusion: LoInc+LoEd was associated with the highest CHD risk at younger ages, but not at higher ages. Income was more important than education for CHD risk at younger ages, but education was more important than income at older ages.