Subsequent Coronary Heart Disease Research Articles

Abstract MP46: Recurrent Hypertensive Disorders of Pregnancy and Subsequent Maternal Coronary Heart Disease and Stroke

Introduction: Hypertensive disorders of pregnancy (HDP) complicate 5-10% of pregnancies and lead to maternal morbidity and mortality. Prior HDP increases HDP risk in subsequent pregnancies with little known about coronary heart disease (CHD) and stroke in recurrent HDP. We aimed to assess the relationship between recurrent HDP and subsequent CHD and stroke. Methods: This retrospective cohort study included women aged 12-49 with one or more singleton, live birth in South Carolina from 2004-2016. Deliveries were evaluated for HDP (preeclampsia, eclampsia, gestational hypertension) defined by birth certificate and/or hospitalization/emergency department (ED) visit data. Women were classified as having no, one, or two or more pregnancies with HDP. Hospitalization/ED visit and death certificate data defined incident CHD and stroke. Extended Cox models with time varying covariates were used to evaluate the association of recurrent HDP with CHD and stroke controlling for sociodemographic, behavioral, and clinical characteristics. Results: The 163,598 women (non-Hispanic White (NHW; 57.8%), non-Hispanic Black (NHB; 33.9%), and Hispanic (8.3%) had two or more (3.3%), one (12.0%), or no (84.7%) HDP pregnancies. Women with recurrent HDP were more likely to develop subsequent CHD or stroke after covariable adjustment (Table 1). Having one or two or more HDP pregnancies compared with no HDP pregnancies increased the subsequent risk of CHD (HR=2.25; 95% CI: 1.97-2.56 and HR=2.98; 95% CI: 2.43-3.67, respectively). Having one or two or more HDP pregnancies compared with no HDP pregnancies increased the subsequent risk of stroke (HR=2.05; 95% CI: 1.61-2.61 and HR=2.97; 95% CI: 2.04-4.32, respectively). Discussion: Women with recurrent HDP are at higher risk of subsequent CHD and stroke. Higher incident CHD and stroke risk appears to persist into the next pregnancy with accumulated HDP conferring higher risk.

Associations of offspring birthweight and placental weight with subsequent parental coronary heart disease: survival regression using the walker cohort.

Low birth weight (BW) is consistently correlated with increased parental risk of subsequent cardiovascular disease, but the links with offspring placental weight (PW) are mostly unexplored. We have investigated the associations between parental coronary heart disease (CHD) and offspring BW and PW using the Walker cohort, a collection of 48,000 birth records from Dundee, Scotland, from the 1950s and 1960s. We linked the medical history of 13,866 mothers and 8,092 fathers to their offspring's records and performed Cox survival analyses modelling maternal and paternal CHD risk by their offspring's BW, PW, and the ratio between both measurements. We identified negative associations between offspring BW and both maternal (hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.88-0.95) and paternal (HR: 0.96, 95% CI: 0.93-1.00) CHD risk, the stronger maternal correlation being consistent with previous reports. Offspring PW to BW ratio was positively associated with maternal CHD risk (HR: 1.14, 95% CI: 1.08-1.21), but the associations with paternal CHD were not significant. These analyses provide additional evidence for intergenerational associations between early growth and parental disease, identifying directionally opposed correlations of maternal CHD with offspring BW and PW, and highlight the importance of the placenta as a determinant of early development and adult disease.

Identification of genetic loci jointly influencing COVID-19 and coronary heart diseases

BackgroundComorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks.MethodsBy leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs).FindingsBriefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18–0.19) to 0.23 (95% CI 0.23–0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks.InterpretationFive SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of ‘Long COVID-19.’

Are physically disabled people at high risk of coronary heart disease among disabled population − Evidence from 7.5-year retrospective cohort study

ObjectivesPrevious cross-sectional studies suggested that people with physical disabilities (one of the subgroups of disabled people) are associated with an increased risk of cardiovascular diseases (CVD) than healthy peers. However, a longitudinal cohort of disabled people exhibited a different trend, in which the study populations were similar in health inequalities. We aimed to examine whether physical disability was associated with an increased risk of coronary heart disease (CHD) among disabled people. Study design and settingThis retrospective cohort study from the Shanghai Health Examination Program included a total of 6419 disabled adults (50.77 [9.88] age) with complete electronic health records and were free of CHD at baseline (2012) were followed-up for a 7.5-year period until 2019. The physical disability and non-physical disability subgroups were characterized based on the Disability Classification and Grading Standard (GB/T 26341–2010). Multivariable Cox regression analyses were used to evaluate adjusted hazard ratios (HR) for subsequent CHD, while Kaplan-Meier curves was used to assess the proportional hazards assumption. We conducted subgroup analyses based on gender, levels of disability, and baseline blood pressure. ResultsKaplan-Meier analysis revealed a higher incidence of CHD in the physical disability group compared to the non-physical disability group during the 7.5-year follow-up period (P < 0.05). Subjects with physical disabilities exhibited an increased risk for subsequent CHD occurrence (HR: 1.12; 95% CI: 1.03–1.31), compared to the non-physical subgroup after adjustments for confounders. The sensitivity analysis conducted on subgroups according to gender and disability severity indicated that moderate physical disability and female physical disability were associated with a higher prevalence of CHD, which was confirmed by multi-adjusted regression analysis. The spline curves of BP and CHD indicated that the physical disability group displayed lower SBP and DBP thresholds of 120 mmHg and SBP, respectively. ConclusionWithin the disabled population, individuals with physical disability are at higher risk of developing CHD, and it is plausible that their optimal BP threshold for CHD prevention may need to be set at a lower level. Further research is essential to investigate BP management among individuals with physical disabilities and its influence on cardiovascular-related adverse events.

Obesity, metabolic health and clinical outcomes after incident cardiovascular disease: A nationwide population-based cohort study.

The association between metabolic syndrome and increased cardiovascular disease (CVD) risk is well-established. However, in patients with incident CVD, the relationship between obesity, metabolic health, and subsequent CVD and mortality outcomes are less well-established. This study investigated the association between body mass index (BMI), metabolic health and the risk of subsequent cardiovascular mortality and morbidity outcomes in patients with incident CVD events. This cohort study identified 130685 patients from the nationwide Clinical Practice Research Datalink (CPRD GOLD) and Hospital Episode Statistics (HES) databases in the United Kingdom. Patients were ≥18years with incident CVD [coronary heart disease (CHD), stroke, or peripheral vascular disease (PVD)] between 1 January 1998 and 31 December 2017. BMI (in kg/m2 ) was categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obese (≥30). Within each BMI category, patients were grouped by increasing count of 1, 2 or 3 metabolic risk factors [RF] (dyslipidaemia, diabetes mellitus and hypertension) and were regarded as metabolically unhealthy while absence of these factors was considered metabolically healthy (MH). Multivariable Cox regression was used to assess the risk (hazard ratio with 95% confidence interval) of subsequent outcomes (non-fatal CHD, stroke, PVD, incident heart failure, CVD-mortality and all-cause mortality) in BMI subgroups with incremental count of metabolic RFs. During a median follow-up of 13.0years, a higher BMI was associated with reduced risk for stroke, PVD, CVD-mortality and all-cause mortality within each metabolic risk category, while increasing metabolic RFs within each BMI subgroup accounted for increasing risks. When compared with patients with normal BMI and no RF, CVD-mortality risk in overweight patients with no RF was 0.76 (0.70-0.84), and in obese patients with no RF was 0.85 (0.76-0.96). The respective risk for all-cause mortality in patients with overweight and no RF was 0.69 (0.65-0.72), and in obese patients with no RF was 0.75 (0.70-0.79). Subsequent outcomes of stroke and PVD showed similar trends. In contrast, the risk of subsequent non-fatal CHD events and incident HF increased with higher BMI and with incremental metabolic risk factors within each BMI category. Underweight was constantly associated with increased risk for all outcomes regardless of the presence of metabolic RFs except for non-fatal CHD events. In patients with incident CVD, overweight and obesity were related to a more favourable prognosis for subsequent stroke, PVD and mortality (CVD-related and all-cause) irrespective of the presence of other metabolic risk factors.

Abstract P194: Proteomic Profiling of Pulmonary Function Decline and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Measures of pulmonary function are associated with cardiovascular disease risk; however, the underlying mechanism remains unclear. Hypothesis: We hypothesize that protein biomarkers are associated with pulmonary function decline, as well as the risk of subsequent incident coronary heart disease (CHD), heart failure (HF), and mortality. Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study with plasma proteome measured by SOMAscan and spirometric measures (forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC)) at both visits 2 (1990-1992) and 5 (2011-2013). Cross-sectional associations of protein levels with FEV1 and FVC at both visits were assessed using multivariable linear regression. The decline of FEV1 was evaluated among proteins related to cross-sectional FEV1 and FVC measures. The FEV1-decline-related proteins were further probed into the effects on incident CHD, HF, and mortality, using Cox proportional hazard models post-visit 2. Results: Out of 4,677 proteins, 364 were cross-sectionally associated with both FEV1 and FVC at visit 2 (n=11,354, age 57, 23% blacks, and 56% women) and 5 (n=3,517, age 75, 17% blacks, and 58% women) at FDR &lt;0.05. Twenty-seven of 364 proteins were associated with FEV1 decline between visits (FDR &lt;0.05). The protein effects were more predominant in women than men (p &lt;0.001). Among 27 FEV1 decline-related proteins, 25 and 27 were associated with incident HF and mortality during an average of 29 years follow-up (FDR &lt;0.05, Figure ). Gamma-aminobutyric acid receptor-associated protein showed the greatest effect with FEV1 decline, and its per SD increase was associated with 20% higher risk of HF and mortality. Compared to HF and mortality, FEV1 decline-related proteins were less associated with incident CHD. Conclusions: Twenty-seven proteins related to pulmonary function decline were heavily associated with the risk of HF and mortality, suggesting shared etiology between those conditions.

Fine particulate matter and incident coronary heart disease events up to 10 years of follow-up among Deepwater Horizon oil spill workers

BackgroundDuring the 2010 Deepwater Horizon (DWH) disaster, in-situ burning and flaring were conducted to remove oil from the water. Workers near combustion sites were potentially exposed to burning-related fine particulate matter (PM2.5). Exposure to PM2.5 has been linked to increased risk of coronary heart disease (CHD), but no study has examined the relationship among oil spill workers. ObjectivesTo investigate the association between estimated PM2.5 from burning/flaring of oil/gas and CHD risk among the DWH oil spill workers. MethodsWe included workers who participated in response and cleanup activities on the water during the DWH disaster (N = 9091). PM2.5 exposures were estimated using a job-exposure matrix that linked modelled PM2.5 concentrations to detailed DWH spill work histories provided by participants. We ascertained CHD events as the first self-reported physician-diagnosed CHD or a fatal CHD event that occurred after each worker's last day of burning exposure. We estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for the associations between categories of average or cumulative daily maximum PM2.5 exposure (versus a referent category of water workers not near controlled burning) and subsequent CHD. We assessed exposure-response trends by examining continuous exposure parameters in models. ResultsWe observed increased CHD hazard among workers with higher levels of average daily maximum exposure (low vs. referent: HR = 1.26, 95% CI: 0.93, 1.70; high vs. referent: HR = 2.11, 95% CI: 1.08, 4.12; per 10 μg/m3 increase: HR = 1.10, 95% CI: 1.02, 1.19). We also observed suggestively elevated HRs among workers with higher cumulative daily maximum exposure (low vs. referent: HR = 1.19, 95% CI: 0.68, 2.08; medium vs. referent: HR = 1.38, 95% CI: 0.88, 2.16; high vs. referent: HR = 1.44, 95% CI: 0.96, 2.14; per 100 μg/m3-d increase: HR = 1.03, 95% CI: 1.00, 1.05). ConclusionsAmong oil spill workers, exposure to PM2.5 from flaring/burning of oil/gas was associated with increased risk of CHD.

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis.

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.

Echocardiographic Features of Patients with Coronary Heart Disease and Angina Pectoris under Deep Learning Algorithms

Based on the VGG19-fully convolutional network (FCN) (VGG19-FCN) and U-Net model in the deep learning algorithms, the left ventricle in the ultrasonic cardiogram was segmented automatically. In addition, this study evaluated the value of ultrasonic cardiogram features after segmentation by the optimized algorithm in diagnosing patients with coronary heart disease (CHD) and angina pectorisody; patients with arrhythmia; and pa. In this study, 30 patients with confirmed CHD and 30 normal people without CHD from the same hospital in a certain area were selected as the research objects. Firstly, the VGG19-FCN and U-Net model algorithms were selected to automatically segment the left ventricular part of the apical four-chamber static image, which was realized through the weights of the fine-tune basic model algorithm. Subsequently, the experimental subjects were divided into a normal group and a CHD group, and the data were obtained through the ultrasonic cardiogram feature analysis of automatic segmentation by the algorithm. The differences in the ejection fraction (EF), left ventricular fractional shortening (FS), and E/A values (in early and late of the diastolic phase) of the left ventricle for patients in the two groups were compared. In addition, the ultrasonic cardiogram left ventricular segmentation results of normal people and patients with CHD were compared. A comprehensive analysis suggested that the U-Net model was more suitable for the practical application of automatic ultrasonic cardiogram segmentation. According to the analyzed data results, the global systolic function parameters (EF, FS, and E/A values) of the left ventricle for patients showed statistically obvious differences ( P &lt; 0.05 ). In summary, deep learning algorithms can effectively improve the efficiency of ultrasonic cardiogram left ventricular segmentation, show a great role in the diagnosis of CHD patients, and provide a reliable theoretical basis and foundation research on the subsequent CHD imaging diagnosis. The comprehensive analysis showed that the U-Net model was more suitable for the practical application of echocardiographic automatic segmentation, and this study can effectively improve the efficiency of echocardiographic left ventricular segmentation, which played an important role in the diagnosis of coronary heart disease, providing a reliable theoretical basis and foundation for subsequent CHD imaging research.

Cost-effectiveness of the CNIC-polypill strategy for the secondary prevention of CV disease in male and female patients with established coronary heart disease based on improved risk factor control

Abstract Background The burden of CV disease is a health and economic challenge to societies that is expected to grow in future years due to an increased prevalence in CV risk factors. Adequate management and appropriate therapy positively modify risk factors and, consequently, improve outcomes and cost-effectiveness of care. The CNIC-polypill has demonstrated in real-life, clinical effectiveness studies, its superiority over monocomponents in improving the lipidic parameters and in reduction of blood pressure in secondary CV prevention patients. Purpose To assess the cost-effectiveness of the CNIC-polypill (acetylsalicylic acid 100mg, atorvastatin 20/40mg, ramipril 2.5/5/10mg) compared to usual care with individual monocomponents for the secondary prevention of CV events in patients with a history of coronary heart disease (CHD) based on control of CV risk factors. Methods A Markov cost-effectiveness model (1-year cycles; 4 health states: stable disease, subsequent CHD, subsequent stroke, death; payer perspective; direct medical costs; lifetime horizon; 4% discount rate) based on changes in TC (10,1% reduction), HDL-c (7.4% increment) and SBP (2.6% reduction) obtained from the NEPTUNO* – a real-life, clinical effectiveness study conducted in Spain – was set for Portugal (base case). The probability of transition between health states was based on the SMART risk equation (S0, t=10= 0.8107). Cost-effectiveness was calculated for a hypothetical population (n=1,000) that replicated the characteristics of the population in the proACS registry, comprised of Portuguese patients with previous CHD. Systematic reviews identified epidemiological, costs, utility and mortality data. Outcomes were costs (€, 2020), life years (LY) and quality adjusted LY (QALY) gained. Results In patients with a history of CHD, the incremental cost of the CNIC-polypill strategy reaches €365,527, while preventing 35 recurrent CHD events and 17 subsequent strokes. In women and men with previous CHD, the incremental cost reaches €392,529 and €354,444 respectively while preventing recurrent 47 and 30 CHD events and 19 and 16 subsequent strokes respectively. The ICER is €5,130/LY gained for the overall population, €5,768/LY gained for women and €4,884/LY gained for men. The ICUR is €5,332/QALY gained in total, €5,817/QALY gained for women and €5,137/QALY gained for men. Assuming a willingness-to-pay (WTP) threshold of €30,000/QALY gained, there is 76.1% chances in total, 75.8% in women and 76.9% in men for the CNIC-polypill to be cost-effective and 27.8% chances overall, 27.7% in women and 25.5% in men of it being cost saving compared to usual care. Conclusion The CNIC-polypill seems to be a cost-effective strategy in men and women compared to usual care with monocomponents for the secondary prevention of CV disease based on improved control of risk factors. A larger reduction in the number of recurrent events is seen in women compared to men at a slightly higher cost. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Ferrer International S.A. Base case resultsProbabilistic sensitivity analysis

Distribution and risk profile of atrial fibrillation patterns among women and men from the general population

Abstract Background In a clinical setting, atrial fibrillation (AF) subgroups are defined, including paroxysmal, persistent, and permanent AF. These subgroups differ in terms of clinical characteristics, management strategy, and long-term outcomes. Application of clinical classifications in population-based settings is challenging as they are based on the duration of symptoms, recurrence, and treatment. Purpose We aim to develop an objective and standardized classification for AF patterns in the general population and examine the associated cardiovascular risk profiles and outcomes for the identified AF patterns. Methods Participants with only one reported AF episode were categorized as single-documented AF, if at least two separate AF episodes were reported as multiple-documented AF and as longstanding persistent AF if at least two consecutive ECG's at the research center showed AF, not followed by an ECG showing sinus rhythm. We fitted mixed effect models with age as time scale to characterize sex-specific cardiovascular risk factor trajectories preceding each AF pattern. We further used Cox proportional hazard modelling to describe the risk of coronary heart disease (CHD), heart failure (HF), stroke, and all-cause mortality following AF. Results We included 14,620 men and women aged ≥45 years. 1137 participants were categorized as single-documented AF, 208 as multiple-documented AF, and 57 as longstanding persistent AF. We identified significant differences in the preceding trajectories of weight, body mass index, systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, and waist-hip ratio with various AF patterns. In general, both men and women with persistent-elevated levels of these risk factors were prone to longstanding persistent AF. AF was associated with a large risk for subsequent CHD, HF, stroke, and mortality in the general population. Among the different AF patterns, single-documented AF conferred the largest risk of CHD [hazard ratio, 95% confidence interval: 1.92 (1.19–3.03)] and mortality [1.70 (1.41–2.07)] as compared to multiple-documented AF, and as compared to longstanding persistent AF [1.45 (0.72–2.90) and 3.66 (2.25–5.95), respectively]. Conclusion We developed a classification for AF patterns within a general population. We identified differences in risk factor trajectories preceding each AF pattern, which implies differences in pathophysiological mechanisms underlying AF. Participants with single-documented AF showed worse prognosis than those with multiple AF episodes. This might be due to the subgroup definition, since participants should live for a longer period of time to be categorized in the multiple-documented AF and longstanding persistent AF groups. This can also imply that participants suffering from multiple AF episodes are more frequently monitored, and treated for other risk factors. However, this could also suggest that singular AF episodes are not as innocent as commonly thought. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): - Erasmus MC Mrace grant. - Netherlands Organization for the Health Research and Development (ZonMw) Figure 1Figure 2. Progosis of various AF patterns

Prevalence and Prognostic Value of Psychological Stress Events in Patients with First Myocardial Infarction-Long-Term Follow-Up Study.

While there is good evidence that symptoms of depression determine prognosis of patients with coronary heart disease (CHD), the role of psychological stress is less clear. We evaluated the prognostic value of stressful events in patients with initial myocardial infarction (MI) with respect to subsequent cardiovascular events. The KAROLA-study included patients with CHD who participated in an in-patient rehabilitation program. A total of 577 patients with initial MI were included and self-reported psychological stressful events before their MI was assessed by a structured questionnaire. Hazard ratios were used to evaluate the long-term association of stressful events with secondary cardiovascular events. Additionally, associations of stressful events with depression, anxiety and other cardiovascular risk factors were investigated. Unusual stress at work (26.5%) and sleep disorder (23.4%) were the most frequently reported stressful events that occurred in the last 4 weeks before MI. However, only death of a family member showed a statistically significant increase in risk for subsequent cardiovascular events (HR: 1.59; 95%-CI: 1.01–2.50) and this result was not corrected for multiple testing. Notably, we found higher symptom scores of anxiety and depression associated with all single stressful event items. In conclusion, we found no clear patterns that psychological stressful events before MI would increase the long-term risk of subsequent adverse CHD events directly. However, we saw increased symptom scores of anxiety and depression in persons with stressful events.

Cost-effectiveness of a cardiovascular polypill strategy (aspirin, atorvastatin, ramipril) for the secondary prevention of cardiovascular disease based on real life improvement in risk factor control

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Ferrer Internacional Background The cardiovascular (CV) polypill has consistently demonstrated cost-effectives in decreasing the risk of CV disease in patients in secondary prevention. Previous pharmacoeconomic studies addressed improvements in adherence as a driver of health gains. This economic assessment focuses on the implications of improved control of risk factors with the polypill as observed in clinical practice. Purpose To assess the cost-effectiveness of a fixed-dose combination polypill (ASA 100mg, atorvastatin 20/40mg, ramipril 2.5/5/10mg) strategy for the secondary prevention of CV and cerebrovascular events in adults with a history of coronary heart disease (CHD) or stroke compared to usual care with monocomponents. Methods A Markov cost-effectiveness model (1-year cycles; 4 health states: stable disease, subsequent CHD, subsequent stroke, death; payer perspective; direct medical costs; lifetime horizon; 4% discount rate) based on changes in CV risk factors (total cholesterol, 18.3% reduction; high density lipoprotein cholesterol, 2.1% increment; systolic blood pressure, 11.46% reduction) obtained from a real-life effectiveness study was set for Portugal. The probability of transition between health states was based on the SMART risk equation. Cost-effectiveness was calculated for two cohorts (n = 1,000) of secondary prevention patients with previous CHD or stroke. Systematic reviews, Portuguese registries, mortality tables and official reports were searched to identify effectiveness, epidemiological, costs and utility data. Outcomes were costs (€, 2020) per life year (LY) and Quality Adjusted LY (QALY) gained. One-way (OWA) and probabilistic (PSA) sensitivity analyses tested consistency. Assumptions were validated by experts. Results In the CHD cohort, the incremental cost-effectiveness ratio for the polypill strategy (ICER) is 2,402 €/LY and the incremental cost-utility ratio (ICUR) is 2,328 €/QALY. Incremental cost reaches 278,927 € (polypill, 13,198,506 €; monocomponents: 12,919,579 €) with less subsequent CV events (552.31 vs 641.88) and CV deaths (102.4 vs 118.68). Assuming a willingness-to-pay (WTP) threshold of 30.000 €/QALY gained, the PSA shows a 81.4% probability for the polypill to be cost-effective and 39.1% chances to be costs saving compared to usual care. In the stroke cohort, the ICER is 386 €/LY and the ICUR is 553 €/QALY. Incremental costs are 34,178 € (polypill, 10,138,807 €; monocomponents: 10,104,629 €) with less subsequent CV events (481.99 vs 564.50) and CV deaths (101.00 vs. 117.23) with the polypill. There is a 75.9% probability for the polypill to be cost-effective and 49.5% chances to be costs saving. Conclusion The CV polypill is a cost-effective secondary prevention strategy compared to usual care with monocomponents. Its ICER is well below acceptable thresholds in both CV and cerebrovascular disease patients. It reduces the number of recurrent events at a moderately higher cost compared to monocomponents.

How consistent are cost-effectiveness estimates of a cardiovascular polypill strategy for the secondary prevention of cardiovascular disease across different cardiovascular risk equations?

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Ferre Internacional Background Risk equations (RE) are crucial to individualise estimates and properly adjust preventive treatments in patients with previous cardiovascular (CV) disease. RE are also routinely incorporated into health economic assessments but it is unknown if the cost-effectiveness results vary according to the RE applied. Purpose To determine the cost-effectiveness of a CV polypill (ASA 100mg, atorvastatin 20/40mg and ramipril 2.5/5/10mg) strategy compared to usual practice of combining monocomponents in the prevention of recurrent events in patients with previous coronary heart disease (CHD) or stroke applying two different CV RE: SMART and FRAMINGHAM, respectively. Methods A Markov cost-effectiveness model (1-year cycles; 4 health states: stable disease, subsequent CHD, subsequent stroke; death; payer perspective; direct medical costs; lifetime horizon; 4% discount rate) was developed for Portugal. Transition probability between health states was based on the SMART RE and an adaptation for secondary CV prevention of the FRAMINGHAM RE, respectively. Cost-effectiveness was calculated for a mixed cohort of secondary prevention patients (weighed post-CHD: 57.9%; post-stroke: 42.1%). Systematic literature reviews, Portuguese registries, mortality tables and official reports ware used to identify effectiveness, epidemiological, costs and utility data. Outcomes were costs (€, 2020) per life year (LY) and Quality Adjusted Life Year (QALY) gained. One-way (OWA) and probabilistic (PSA) sensitivity analyses tested the consistency of results. Assumptions were validated by experts. Results Applying the SMART RE, the incremental cost-effectiveness ratio (ICER) is 1,555€/LY gained and the incremental cost-utility ratio (ICUR) is 1,785€/QALY gained for the polypill strategy. The incremental costs of adopting the polypill strategy are 171,378€. Recurrent CV events (550.68 vs 642.13) and CV deaths (106.05 vs 122.81) are also less frequent with the polypill strategy compared with monocomponents. Assuming a willingness-to-pay (WTP) threshold of 30.000 €/QALY gained, there is a 77.80% probability for the polypill strategy to be cost-effective and 43.00% chances to be costs saving when used in a mixed cardiovascular and cerebrovascular disease population. Applying the FRAMINGHAM RE, the ICER is 998€/LY gained and the ICUR is 1,242€/QALY. The incremental costs amount 175,122€. Recurrent CV events (452.66 vs 563.48) and CV deaths (104.77 vs 127.32) are less frequent with the polypill strategy. The PSA shows a 99.5% probability for the polypill strategy to be cost-effective and 46.8% chances to be costs saving. Conclusion Both risk equations result in comparable results on the cost-effectiveness of interventions for the secondary prevention of CV disease. The polypill strategy remains cost-effective compared to the common practice of using individual monocomponents concomitantly, reducing recurrent CV events at a moderately higher cost.

Association of Mid- to Late-Life Blood Pressure Patterns With Risk of Subsequent Coronary Heart Disease and Death.

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.

Association of small, dense LDL-cholesterol concentration and lipoprotein particle characteristics with coronary heart disease: A systematic review and meta-analysis.

The aim of this study was to systematically collate and appraise the available evidence regarding the associations between small, dense low-density lipoprotein (sdLDL) and incident coronary heart disease (CHD), focusing on cholesterol concentration (sdLDL-C) and sdLDL particle characteristics (presence, density, and size). Coronary heart disease (CHD) is the leading cause of death worldwide. Small, dense low-density lipoprotein (sdLDL) has been hypothesized to induce atherosclerosis and subsequent coronary heart disease (CHD). However, the etiological relevance of lipoprotein particle size (sdLDL) versus cholesterol content (sdLDL-C) remains unclear. PubMed, MEDLINE, Web of Science, and EMBASE were systematically searched for studies published before February 2020. CHD associations were based on quartile comparisons in eight studies of sdLDL-C and were based on binary categorization in fourteen studies of sdLDL particle size. Reported hazards ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) were standardized and pooled using a random-effects meta-analysis model. Data were collated from 21 studies with a total of 30,628 subjects and 5,693 incident CHD events. The average age was 67 years, and 53% were men. Higher sdLDL and sdLDL-C levels were both significantly associated with higher risk of CHD. The pooled estimate for the high vs. low categorization of sdLDL was 1.36 (95% CI: 1.21, 1.52) and 1.07 (95% CI: 1.01, 1.12) for comparing the top quartiles versus the bottom of sdLDL-C. Several studies suggested a dose response relationship. The findings show a positive association between sdLDL or sdLDL-C levels and CHD, which is supported by an increasing body of genetic evidence in favor of its causality as an etiological risk factor. Thus, the results support sdLDL and sdLDL-C as a risk marker, but further research is required to establish sdLDL or sdLDL-C as a potential therapeutic marker for incident CHD risk reduction.

Identifying Mean Heart Dose Thresholds for Proton Therapy Acceptability in Mediastinal Unfavorable Early-Stage Hodgkin Disease

Proton beam therapy (PBT) decreases radiation doses to healthy tissues distal to the target when compared with intensity-modulated photon radiotherapy (IMRT). This physical property is particularly important for mediastinal Hodgkin lymphomas (MHL), wherein tumors approximate the heart, since higher mean heart doses (MHDs) are associated with a higher incidence of coronary heart disease (CHD). Yet, PBT is more expensive than IMRT, and fewer centers offer PBT. In the absence of long-term clinical data, we sought to determine the MHD thresholds at which PBT would become cost-effective and the effect of age on acceptability, given the bimodal distribution of MHL. We evaluated MHD thresholds for PBT versus IMRT for treatment of MHL to 30.6 Gy. We created a Markov cohort model under which patients age 30 years would possibly experience several health states for which CHD was modified by MHD between RT modalities: health, relapse, CHD, and death. Relapse risk was informed by HD14, and MHD-CHD probability was informed by van Nimwegen et al. CHD baseline risk used Framingham data and differed between men and women. Costs, calculated from a payer perspective were in 2018 USD. Effectiveness was measured in quality-adjusted life years (Q), and the discount rate was 3%. The model terminated at age 80 years, above which Framingham rates are not reported. The model results are reported using incremental cost-effectiveness ratios (ICERs) using willingness to pay (WTP) thresholds of $100K/Q and $200K/Q. We evaluated acceptability at 30 and 60 years of age. Model calibration corroborated estimates from HD14 and van Nimwegen. Results are shown in the table with cells illustrating a given proton MHD threshold of cost acceptability for a given photon MHD comparator, e.g. for a photon MHD of 15Gy, proton therapy was acceptable for a 60-year-old man with an MHD of 12.3 CGE at WTP $100K/Q. With WTP $100K/Q, an MHD reduction of 5, 4, and 3 Gy yielded PBT acceptability in 100%, 75%, and 38% of scenarios, respectively. With WTP $200K/Q, an MHD reduction of 5, 4, 3 and 2 Gy yielded PBT acceptability in 100%, 100%, 100%, and 75% of scenarios, respectively. We present evidence to help establish comparative thresholds for PBT acceptability based on risk of subsequent CHD in the absence of long-term clinical data. Age had minimal impact on PBT acceptability. MHD thresholds in men were higher than those in women given their higher baseline risk of CHD. Future studies should include other toxicities like secondary breast cancer, sarcoma, congestive heart failure, and lung disease.Tabled 1Abstract 2907; TablePhoton MHD (Gy)30 year olds60 year oldsMENWOMENMENWOMEN$100K/Q$200K/Q$100K/Q$200K/Q$100K/Q$200K/Q$100K/Q$200K/Q52.63.612.82.83.81.93.3107.38.55.87.77.68.66.78.2151213.310.612.712.313.511.613.22016.818.215.417.617.118.316.518.12521.42320.322.521.823.221.323 Open table in a new tab

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.

Association of Body Mass Index With Coronary Artery Calcium and Subsequent Cardiovascular Mortality: The Coronary Artery Calcium Consortium.

Obesity is associated with higher risk for coronary artery calcium (CAC), but the relationship between body mass index (BMI) and mortality is complex and frequently paradoxical. We analyzed BMI, CAC, and subsequent mortality using data from the CAC Consortium, a multi-centered cohort of individuals free of established cardiovascular disease (CVD) who underwent CAC testing. Mortality was assessed through linkage to the Social Security Death Index and cause of death from the National Death Index. Multivariable logistic regression was used to determine odds ratios for the association of clinically relevant BMI categories and prevalent CAC. Cox proportional hazards regression modeling was used to determine hazard ratios for coronary heart disease, CVD, and all-cause mortality according to categories of BMI and CAC. Our sample included 36 509 individuals, mean age 54.1 (10.3) years, 34.4% female, median BMI 26.6 (interquartile range, 24.1-30.1), 46.6% had zero CAC, and 10.5% had CAC ≥400. Compared with individuals with normal BMI, the multivariable adjusted odds of CAC >0 were increased in those overweight (odds ratio, 1.13 [95% CI, 1.1-1.2]) and obese (odds ratio, 1.5 [95% CI, 1.4-1.6]). Over a median follow-up of 11.4 years, there were 1550 deaths (4.3%). Compared with normal BMI, obese individuals had a higher risk of coronary heart disease, CVD, and all-cause mortality while overweight individuals, despite a higher odds of CAC, showed no significant increase in mortality. In a sex-stratified analysis, the increase in coronary heart disease, CVD, and all-cause mortality in obese individuals appeared largely limited to men, and there was a lower risk of all-cause mortality in overweight women (hazard ratio, 0.79 [95% CI, 0.63-0.98]). In a large sample undergoing CAC scoring, obesity was associated with a higher risk of CAC and subsequent coronary heart disease, CVD, and all-cause mortality. However, overweight individuals did not have a higher risk of mortality despite a higher risk for CAC.

Frequency of daily tooth brushing and subsequent cardiovascular events.

Although previous studies have shown an inverse association between the frequency of daily tooth brushing and cardiovascular risk factors, research on cardiovascular events is limited. This study aimed to evaluate the association between the frequency of daily tooth brushing and subsequent cardiovascular events. A retrospective longitudinal study was conducted at a hospital in Tokyo, Japan. We included all participants who underwent health check-ups from 2005 to 2011 and followed up to 2018. Our outcomes were the development of cardiovascular events. Outcomes were compared by the frequency of daily tooth brushing with a generalized estimating equation, adjusting for potential confounders. A total of 71 221 participants were included. The mean age was 45.6 years and 50.3% were male. During a median follow-up of 2061 (interquartile range: 933-3311) days, 1905 participants developed cardiovascular events. The adjusted odds ratios (ORs) of cardiovascular events increased in a dose-dependent manner as the frequency of tooth brushing decreased. Even those who brushed their teeth once in a day had a higher adjusted OR of stroke (1.22; 95% confidence interval, 1.01-1.48) than did those who brushed after every meal. Frequent tooth brushing was inversely associated with subsequent cardiovascular events in a dose-dependent manner. Even brushing one's teeth once a day may be related to an increased likelihood of stroke than brushing one's teeth after every meal. Less frequent tooth brushing may be considered to be a marker for subsequent cardiovascular disease and coronary heart disease, rather than a risk factor.