Incidence Of Coronary Events Research Articles

The Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations.

Clonal hematopoiesis (CH) is defined by the expansion of a lineage of genetically identical cells in blood. Genetic lesions that confer a fitness advantage, such as point mutations or mosaic chromosomal alterations (mCAs) in genes associated with hematologic malignancy, are frequent mediators of CH. However, recent analyses of both single cell-derived colonies of hematopoietic cells and population sequencing cohorts have revealed CH frequently occurs in the absence of known driver genetic lesions. To characterize CH without known driver genetic lesions, we used 51,399 deeply sequenced whole genomes from the NHLBI TOPMed sequencing initiative to perform simultaneous germline and somatic mutation analyses among individuals without leukemogenic point mutations (LPM), which we term CH-LPMneg. We quantified CH by estimating the total mutation burden. Because estimating somatic mutation burden without a paired-tissue sample is challenging, we developed a novel statistical method, the Genomic and Epigenomic informed Mutation (GEM) rate, that uses external genomic and epigenomic data sources to distinguish artifactual signals from true somatic mutations. We performed a genome-wide association study of GEM to discover the germline determinants of CH-LPMneg. After fine-mapping and variant-to-gene analyses, we identified seven genes associated with CH-LPMneg (TCL1A, TERT, SMC4, NRIP1, PRDM16, MSRA, SCARB1), and one locus associated with a sex-associated mutation pathway (SRGAP2C). We performed a secondary analysis excluding individuals with mCAs, finding that the genetic architecture was largely unaffected by their inclusion. Functional analyses of SMC4 and NRIP1 implicated altered HSC self-renewal and proliferation as the primary mediator of mutation burden in blood. We then performed comprehensive multi-tissue transcriptomic analyses, finding that the expression levels of 404 genes are associated with GEM. Finally, we performed phenotypic association meta-analyses across four cohorts, finding that GEM is associated with increased white blood cell count and increased risk for incident peripheral artery disease, but is not significantly associated with incident stroke or coronary disease events. Overall, we develop GEM for quantifying mutation burden from WGS without a paired-tissue sample and use GEM to discover the genetic, genomic, and phenotypic correlates of CH-LPMneg.

High-Density Lipoprotein Particle Concentration and Size Predict Incident Coronary Artery Disease Events in a Cohort With Type 1 Diabetes.

The cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for cholesterol efflux capacity, perhaps mediated through efflux of cholesterol and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People with type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL-cholesterol concentrations. We therefore tested the hypothesis that small HDL particles (HDL-P)-rather than HDL-cholesterol-predict incident CAD in type 1 diabetes. Incident CAD (CAD death, myocardial infarction, or coronary revascularization) was determined in 550 individuals with childhood-onset type 1 diabetes. HDL-P was quantified by calibrated ion mobility analysis and cholesterol efflux capacity was quantified with validated assays. During a median follow-up of 26 years, 36.5% of the participants developed incident CAD, for an incidence density of 181.3 per 10 000 person-years. In multivariable Cox models, neither HDL-cholesterol nor apolipoprotein A1 concentration was significantly associated with CAD risk. In contrast, higher extra-small HDL-P concentrations were significantly associated with decreased CAD risk (hazard ratio [HR], 0.26 [95% CI, 0.14-0.50]). Weaker associations were observed for total HDL-P (HR, 0.88 [95% CI, 0.83-0.93]), small HDL (HR, 0.83 [95% CI, 0.68-1.02]), medium HDL (HR, 0.79 [95% CI, 0.71-0.89]), and large HDL (HR, 0.72 [95% CI, 0.59-0.89]). Although cholesterol efflux capacity was negatively associated with incident CAD, this association was no longer significant after adjustment for total HDL-P. Lower concentrations of total HDL-P and HDL subpopulations were positively associated with incident CAD independently of HDL-cholesterol, apolipoprotein A1, and other common CVD risk factors. Extra-small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that extra-small HDL plays a critical role in cardioprotection in type 1 diabetes, mediated by macrophage cholesterol efflux by the ABCA1 pathway.

Approaches to therapy Amlodipine/Indapamide/Perindopril therapy of high arterial hypertension in ischemic heart disease patients with chronic kidney disease stage 1-3 after coronary stenting

Introduction: Acute coronary syndrome, chronic forms of ischemic heart disease (IHD) and postinfarction cardiosclerosis are the main causes of morbidity and mortality in the world, including Russia. In the XXI century, there is an increase in comorbid pathology, especially in the combination of IHD with arterial hypertension, diabetes, chronic obstructive pulmonary disease and chronic kidney disease. Patients with IHD and chronic kidney disease have a higher incidence of coronary events and complications. The frequency of coronary events and complications indicates the need to improve the diagnosis and treatment of this group of patients. diagnosis and treatment of this group of patients. The aim of the study was to analyze the dynamics of vascular stiffness, pulmonary hypertension (PH), diastolic heart dysfunction and endothelial dysfunction indices in patients with different variants of ischemic heart disease combined with chronic kidney disease (CKD) stage 1-3 using complex therapy of combined hypotensive drug Amlodipine/Indapamide/Perindopril three months after coronary stenting and to compare them with the group of patients on conservative therapy only. Materials and Methods: 85 patients with different forms of IHD, arterial hypertension (AH) on the background of CKD 1-3 stages, as well as data of 42 patients with IHD, AH without renal pathology were analyzed. The first group – IHD, postinfarction cardiosclerosis, CKD stage 1-3 (33 patients); the second group – acute coronary syndrome with ST-segment elevation, Myocardial infarction (MI) (30 patients); the third group – ACS without ST-segment elevation, Unstable angina (UA) (22 patients). Results: The highest indices of vascular stiffness (Pulse wave velocity (PWV), Augmentation index (AI), CAVI, Central Systolic Blood Pressure (SBPao), central arterial pulse pressure (PP)) were registered in combination of ACS with ST-segment elevation and CKD 1-3 stages. These indices are markers of IHD progression in these patients; they also have increased pulmonary hypertension and diastolic dysfunction of the heart, endothelial dysfunction with vasodilation insufficiency in 88% of cases, which even without hemodynamically significant coronary artery stenoses according to coronary CT angiography data leads to the development of ACS with ST-segment elevation and ACS without ST-segment elevation with MI. Amlodipine/Indapamide/Perindopril was prescribed to all patients due to high arterial hypertension on admission against the background of basic therapy of IHD and coronary stenting. Coronary CT angiography in patients with comorbid renal pathology does not lead to aggravation of chronic kidney disease after 3 months, on the contrary; in this group of patients the most pronounced decrease of arterial stiffness (AS), AI, SBPao, PP with elevation of glomerular filtration rate (GFR) and decrease of creatinine in blood occurs in comparison with the group of patients who did not undergo coronary stenting, they were only on conservative therapy. Conclusion: Prescription of three component drug Amlodipine/Indapamide/Perindopril on the background of baseline therapy especially in combination with surgical vascularization of the heart is justified.

#1440 Analysis of risk factors for the development of coronary events in patients with chronic kidney disease stage 5

Abstract Background and Aims To analyze the number and presence of certain risk factors for the development of coronary events in patients with chronic kidney disease receiving program hemodialysis. Method To achieve this goal, we first conducted an information search in electronic databases of articles: in English - in PubMed, the search depth was from 2010 to 2020, after which we selected the most common risk factors for the development of coronary events in the conditions of Uzbekistan (Table 1). The study and recruitment of patients took place in the department of nephrology and hemodialysis of the Republican Specialized Scientific and Practical Medical Center for Nephrology and Kidney Transplantation in 2023. The study involved 73 (42.95%) men and 97 (57.05%) women; the average age of the patients was 54.00 ± 13.72 years. The main causes of chronic renal failure in the structure of the overall morbidity of the prospective study were: diabetic nephropathy - 41% (69), chronic glomerulonephritis - 40% (68), chronic pyelonephritis - 12.9% (22). Results All 170 patients were assessed for risk factors for the development of coronary events according to Table 1. Based on the current literature, we selected 30 risk factors for the development of coronary events. The most common risk factors for the development of coronary events were, that is, 2/3: albumin, body mass index, calcium, cardiovascular diseases, clinical and ambulatory blood pressure, chronic heart failure, diastolic blood pressure, hemoglobin, left ventricular hypertrophy, mean arterial pressure, systolic blood pressure, diuretic (urea), years with hypertension. The least significant risk factors for the development of coronary events were, that is, 1/3: diabetes, diabetic nephropathy, dyslipidemia, coronary heart disease, left ventricular end-diastolic volume, metabolic syndrome, parathyroid hormone, peripheral vascular disease, phosphorus, potassium, pulse pressure, sodium (in plasma), sodium-potassium ratio, smoking, total cholesterol. Conclusion In 2/3 of the studied patients of the main group, the presence of 15 risk factors for the development of coronary events was noted, in 1/3 of the patients, 21 risk factors for the development of coronary events were identified. The above risk factors together increase the incidence of coronary events in patients with stage 5 CKD several times. Coronary events are the leading causes of death in all groups. The most common were: acute left ventricular failure and sudden cardiac death. And predictors of the risk factor for death for coronary events include: blood albumin levels, BMI, blood hemoglobin, LVH, SBP, DAS, CHF, blood calcium, years since hypertension.

Rigidez carotídea y riesgo de eventos vasculares y mortalidad: el estudio REGICOR

Introduction and objectivesThe aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. MethodsPopulation-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. ResultsCarotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,−33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. ConclusionsCarotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions.

Vascular Age Assessed From an Uncalibrated, Noninvasive Pressure Waveform by Using a Deep Learning Approach: The AI-VascularAge Model.

Aortic stiffness, assessed as carotid-femoral pulse wave velocity, provides a measure of vascular age and risk for adverse cardiovascular disease outcomes, but it is difficult to measure. The shape of arterial pressure waveforms conveys information regarding aortic stiffness; however, the best methods to extract and interpret waveform features remain controversial. We trained a convolutional neural network with fixed-scale (time and amplitude) brachial, radial, and carotid tonometry waveforms as input and negative inverse carotid-femoral pulse wave velocity as label. Models were trained with data from 2 community-based Icelandic samples (N=10 452 participants with 31 126 waveforms) and validated in the community-based Framingham Heart Study (N=7208 participants, 21 624 waveforms). Linear regression rescaled predicted negative inverse carotid-femoral pulse wave velocity to equivalent artificial intelligence vascular age (AI-VA). The AI-VascularAge model predicted negative inverse carotid-femoral pulse wave velocity with R2=0.64 in a randomly reserved Icelandic test group (n=5061, 16%) and R2=0.60 in the Framingham Heart Study. In the Framingham Heart Study (up to 18 years of follow-up; 479 cardiovascular disease, 200 coronary heart disease, and 213 heart failure events), brachial AI-VA was associated with incident cardiovascular disease adjusted for age and sex (model 1; hazard ratio, 1.79 [95% CI, 1.50-2.40] per SD; P<0.0001) or adjusted for age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, prevalent diabetes, hypertension treatment, and current smoking (model 2; hazard ratio, 1.50 [95% CI, 1.24-1.82] per SD; P<0.0001). Similar hazard ratios were demonstrated for incident coronary heart disease and heart failure events and for AI-VA values estimated from carotid or radial waveforms. Our results demonstrate that convolutional neural network-derived AI-VA is a powerful indicator of vascular health and cardiovascular disease risk in a broad community-based sample.

Carotid artery stiffness and risk of vascular events and mortality: the REGICOR study

Introduction and objectivesThe aims of this study were to determine the dose-response association of carotid arterial stiffness with vascular outcomes and overall mortality, and to assess their added predictive capacity. MethodsPopulation-based cohort study including 6468 individuals, with a median follow-up of 6.5 years. Six carotid artery stiffness indices were assessed: strain, stiffness, Peterson elasticity coefficient, compliance coefficient, distensibility coefficient, and pulse wave velocity (PWV). Incident coronary, cerebrovascular, global vascular, and total fatal events were identified. ResultsCarotid compliance and distensibility coefficients were not associated with any of the outcomes. Carotid stiffness, Peterson elasticity coefficient, and PWV showed a direct linear relationship to cerebrovascular disease: the risk increased by 8% (95%CI, 1-16) per stiffness unit increase, by 7% (95%CI, 2-13) per 10-unit Peterson elasticity coefficient increase, and by 26% (95%CI, 8-48) per PWV unit increase. Carotid strain showed a nonlinear association with ischemic heart disease. When strain was ≤ 0.09 units, each 0.01-unit increase was associated with a 15% lower risk of coronary events (95%CI,−33 to 6); above 0.09 units, each 0.01 increase in strain was associated with a 16% higher risk of coronary events (95%CI, 6-27). The addition of the stiffness indices did not improve the predictive capacity of validated risk functions. ConclusionsCarotid stiffness, Peterson elasticity coefficient, and PWV have a direct linear association with cerebrovascular disease risk. Carotid strain is not linearly related to U-shaped ischemic heart disease risk. The inclusion of these indexes does not improve the predictive capacity of risk functions.

Invariant natural killer T cells and incidence of first-time coronary events: a nested case-control study.

Invariant natural killer T (iNKT) cells, a T cell subset that is CD1d-restricted and expresses a semi-invariant T cell receptor, have been proposed to contribute to dyslipidaemia-driven cardiovascular disease due to their ability to specifically recognize lipid antigens. Studies in mice have attributed pro-atherogenic properties to iNKT cells, but studies in humans investigating associations of iNKT cells with incident coronary events (CE) are lacking. Here, we used flow cytometry to enumerate circulating iNKT cells (CD3+ CD1d-PBS57-Tetramer+) in a case-control cohort nested within the prospective population-based Malmö Diet and Cancer Study (n = 416) to explore associations with incident first-time CE during a median follow-up of 14 years. We found a significant inverse association between CD4- and CD8- double negative (DN) iNKT cells and incident CE, with an odds ratio of 0.62 [95% confidence interval (CI) 0.38-0.99; P = 0.046] comparing the highest vs. the lowest tertile of DN iNKT cells. The association remained significant after adjustment for cardiovascular risk factors with an odds ratio of 0.57 (95% CI 0.33-0.99; P = 0.046). In contrast, total iNKT cells were not significantly associated with incident CE after adjustment, with an odds ratio of 0.74 (95% CI 0.43-1.27; P = 0.276). Our findings indicate that animal studies suggesting an atherosclerosis-promoting role for iNKT cells may not translate to human cardiovascular disease as our data show an association between high circulating numbers of DN iNKT cells and decreased risk of incident CE.

Elevated circulating follistatin associates with increased risk of mortality and cardiometabolic disorders

Background and aimsPrevious study showed that elevated circulating hepatokine follistatin (FST) associates with an increased risk of type 2 diabetes by inducing adipose tissue insulin resistance. Here we explore further the relationships between plasma FST levels with mortality and health outcomes. Methods and resultsThe population-based Malmö Diet Cancer cardiovascular cohort (n = 4733, age 45–68 years) was used to study plasma FST in relation to incidence of health outcomes, by linkage with national patient registers. Cox regression analysis was used to assess the associations of plasma FST and outcomes, with adjustments for multiple potential confounding factors. During the mean follow-up time of 22.64 ± 5.84 years in 4,733 individuals, 526 had incident stroke, 432 had ischemic stroke, 530 had incident coronary events (CE), 339 had incident heart failure (HF), 320 had incident chronic kidney disease (CKD) and 1,843 individuals died. Hazard ratio (HR) per standard deviation increase in FST levels adjusted for multiple risk factors was 1.05 (95%CI: 1.00–1.11, p = 0.036) for mortality; 1.10 (95%CI: 1.00–1.20, p = 0.042) for stroke; 1.13 (95%CI: 1.03–1.25, p = 0.014) for ischemic stroke; 1.16 (95%CI: 1.03–1.30, p = 0.015) for HF; and 1.38 (95%CI: 1.12–1.70, p = 0.003) for a diagnosis of CKD. In MDC-CC individuals without prevalent or incident diabetes, the association between FST and stroke, CE and CKD remained significant; but not with mortality or HF. ConclusionsElevated circulating FST associates with an increased risk of mortality and HF, which partly may be mediated by diabetes. FST also associated with stroke, ischemic stroke, CE and CKD, independently of established risk factors including diabetes.

High consumption of dairy products and risk of major adverse coronary events and stroke in a Swedish population.

The association between the consumption of dairy products and risk of CVD has been inconsistent. There is a lack of studies in populations with high intakes of dairy products. We aimed to examine the association between intake of dairy products and risk of incident major adverse coronary events and stroke in the Swedish Malmö Diet and Cancer cohort study. We included 26190 participants without prevalent CVD or diabetes. Dietary habits were obtained from a modified diet history, and endpoint data were extracted from registers. Over an average of 19 years of follow-up, 3633 major adverse coronary events cases and 2643 stroke cases were reported. After adjusting for potential confounders, very high intakes of non-fermented milk (>1000 g/d) compared with low intakes (<200 g/d) were associated with 35 % (95 % CI (8, 69)) higher risk of major adverse coronary events. In contrast, moderate intakes of fermented milk (100-300 g/d) were associated with a lower risk of major adverse coronary events compared with no consumption. Intakes of cheese (only in women) and butter were inversely associated with the risk of major adverse coronary events. We observed no clear associations between any of the dairy products and stroke risk. These results highlight the importance of studying different dairy foods separately. Further studies in populations with high dairy consumption are warranted.

Volatile Hydrocarbon Exposures and Incident Coronary Heart Disease Events: Up to Ten Years of Follow-up among Deepwater Horizon Oil Spill Workers.

During the 2010 Deepwater Horizon (DWH) disaster, response and cleanup workers were potentially exposed to toxic volatile components of crude oil. However, to our knowledge, no study has examined exposure to individual oil spill-related chemicals in relation to cardiovascular outcomes among oil spill workers. Our aim was to investigate the association of several spill-related chemicals [benzene, toluene, ethylbenzene, xylene, n-hexane (BTEX-H)] and total hydrocarbons (THC) with incident coronary heart disease (CHD) events among workers enrolled in a prospective cohort. Cumulative exposures to THC and BTEX-H across the cleanup period were estimated via a job-exposure matrix that linked air measurement data with self-reported DWH spill work histories. We ascertained CHD events following each worker's last day of cleanup work as the first self-reported physician-diagnosed myocardial infarction (MI) or a fatal CHD event. We estimated hazard ratios (HR) and 95% confidence intervals for the associations of exposure quintiles (Q) with risk of CHD. We applied inverse probability weights to account for bias due to confounding and loss to follow-up. We used quantile g-computation to assess the joint effect of the BTEX-H mixture. Among 22,655 workers with no previous MI diagnoses, 509 experienced an incident CHD event through December 2019. Workers in higher quintiles of each exposure agent had increased CHD risks in comparison with the referent group (Q1) of that agent, with the strongest associations observed in Q5 (range of ). However, most associations were nonsignificant, and there was no evidence of exposure-response trends. We observed stronger associations among ever smokers, workers with education, and workers with body mass index . No apparent positive association was observed for the BTEX-H mixture. Higher exposures to volatile components of crude oil were associated with modest increases in risk of CHD among oil spill workers, although we did not observe exposure-response trends. https://doi.org/10.1289/EHP11859.

Polygenic score: An anchor holding the whole life course.

Polygenic score: An anchor holding the whole life course.

Plasma levels of CCL21, but not CCL19, independently predict future coronary events in a prospective population-based cohort

Background and aimsThe homeostatic chemokines CCL21 and CCL19 have been explored as biomarkers in cardiovascular disease prediction in patients with established cardiovascular disease, but associations between these chemokines and first-time coronary event incidence have not been investigated before. Here, we explored associations between CCL21 or CCL19 and first-time incident coronary events in the general population-based Malmö Diet and Cancer cohort with two decades of follow-up. MethodsCCL21 and CCL19 levels in plasma were analysed with ELISA and proximity extension assay and associations with disease incidence were explored with conditional logistic regression in a nested case-control cohort (CCL21; n = 676) and with Cox regression in a population-based cohort (CCL19; n = 4636). ResultsHigh CCL21 levels in plasma were associated with incident first-time coronary events independently of traditional risk factors (odds ratio of 2.64 with 95% confidence interval 1.62–4.31, p < 0.001, comparing the highest versus the lowest tertile of CCL21), whereas CCL19 was not. CCL19 was, however, associated with incident heart failure, as well as increased all-cause, cardiovascular and cancer mortality independently of age and sex. ConclusionsEven though CCL21 and CCL19 both signal through CCR7, these chemokines may not be interchangeable as disease predictors and CCL21 could be used for prediction of future coronary events in individuals without any previous coronary heart disease history.

ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION IN A YOUNG PATIENT WITH IGA NEPHROPATHY: A RARE CASE REPORT

&#x0D; Cardiovascular events are less commonly described in glomerular disease. However, thromboembolic events are quite commonly reported in glomerular disease with nephrotic range proteinuria. Here, we report a case of a 29 years old male with IgA nephropathy present with central chest pain radiating to the jaw. He was under mycophenolate, prednisolone and losartan with remission of proteinuria for two months. ECG showed extensive ST segment elevation in V1- V6 leads. His cardiac troponins were elevated. Coronary angiography showed complete thrombotic occlusion of mid left anterior descending artery which was successfully recanalized after primary percutaneous intervention. Though less commonly reported in literature, such incidence of coronary events in IgA nephropathy can rarely present with acute myocardial infarction.

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.

Abstract 13083: Lipoprotein(a) is a Residual Cardiovascular Risk Factor in Statin Treated Stroke Survivors - Insights From the SPARCL Trial

Introduction: Elevated lipoprotein (a) [Lp(a)] plasma levels are causally associated with CAD. The association between Lp(a) and stroke is however less clear. The SPARCL trial has demonstrated the superiority of 80mg atorvastatin to placebo for the prevention of stroke in patients with recent stroke or TIA. The aim of the current study was to investigate if Lp(a) is predictive of recurrent cerebrovascular and incident coronary events in these patients. Methods: Lp(a) concentration and apolipoprotein(a) [apo(a)] isoform size, a strong determinant of Lp(a) plasma levels, were measured by LC-HRMS in samples collected at baseline from 2814 SPARCL participants (1418 randomized to atorvastatin &amp; 1396 to placebo). Within each treatment arm, we compared patients in the highest quartile ( &gt;84.0nmol/L ) with those in the lowest quartiles of Lp(a) concentrations and patients in the lowest quartile ( &lt;25.9 KIV domains ) with those in the highest quartiles of apo(a) size distributions. The relationship between these parameters and subsequent events was established with a Cox proportional hazard model adjusted for age, sex, type of entry event, time since entry event, BMI, smoking, hypertension, non HDLC and DM. Results: In patients randomized to atorvastatin, elevated Lp(a) concentrations and shorter apo(a) isoforms were independently associated with an increased risk of coronary events [HR (95% CI) of 1.607 (1.007-2.563) p=0.047 &amp; 2.052 (1.303-3.232) p=0.002 , respectively]. These associations were primarily driven by a significantly higher incidence of coronary revascularisation procedures, stable angina requiring hospitalization, and MI. No such association was found in patients randomized to placebo [0.925 (0.606-1.412) &amp; 1.105 (0.735-1.659)]. We did not observe any significant association between elevated Lp(a) concentrations or short apo(a) isoforms and the risk of recurrent cerebrovascular events in patients randomized to atorvastatin [0.794 (0.586-1.076) &amp; 1.114 (0.760-1.352)] or placebo [0.914 (0.688-1.214) &amp; 0.940 (0.709-1.248)]. Conclusion: Lp(a) contributes to the residual CAD risk of statin-treated stroke/TIA survivors, paving the way for the use of novel therapies targeting Lp(a) in patients with a history of stroke and elevated Lp(a).

Abstract 13386: The Association of High Polygenic Risk With Future Coronary Heart Disease Events Diminishes Later in Life

Introduction: Polygenic risk scores (PRS) for coronary heart disease (CHD) are associated with incident CHD events. We assessed whether the strength of this association differs over the life course. Methods: We studied 7,958 genotyped participants of European-ancestry without CHD enrolled in the Atherosclerosis Risk in Communities Study (ARIC). Participants were 45-64 years old at the baseline visit occurring 1987-89 with follow up available through 2015. A genome-wide PRS for CHD composed of 1.7 million variants was computed for each participant. Incident CHD was defined as clinically adjudicated myocardial infarction including silent infarction, coronary revascularization, or fatal coronary event. An extended Cox model was constructed with age as the model time scale. The association of PRS with incident CHD was assumed to be log-linear and further modeled as a function of age assuming differing piecewise constant effect sizes across the intervals ≤55, 55-65, 65-80, and ≥80 years. The regression model also included the following covariates: sex, systolic blood pressure, total and HDL cholesterol, history of diabetes, antihypertensive medication use, and smoking status. Results: In the ARIC cohort (median enrollment age 54, interquartile range [IQR] 49-59, female 52%), over a median of 24.5 years (IQR 14.4-28.1), there were 1,872 incident CHD events. In comparison to average polygenic risk for CHD (50th percentile of PRS distribution), harboring high polygenic risk (95th percentile) was associated with a 2.9-fold increased risk of incident CHD (95% CI 2.12-3.95) up to age 55 years, independent of conventional risk factors. The strength of association was attenuated later in life (Hazard ratio, age 55-65, 2.5 [2.14-2.84]; age 65-80, 1.87 [1.68-2.07]; age ≥80, 1.78 [1.38-2.31]) Conclusions: A genome-wide PRS for CHD is more strongly associated with incident coronary events at younger age. The strength of association declined later in life while remaining significant. The age-dependent association of PRS with CHD may need to be accounted for in risk prediction models.

Impact of Lubrizol factory fire in Rouen on coronary events: A retrospective study from the France PCI registry

On September 26, 2019, an industrial fire occurred in the Lubrizol factory in Rouen (France), exposing the population to the inhalation of many volatile toxic agents secondary to combustion. To assess its impact on the incidence of coronary artery events. All coronary angiography performed in Rouen (exposed) and Le Havre (unexposed) from January 2019 and December 2019 were extracted from the prospective FRANCE-PCI registry. To study the impact of the fire on coronary events, an interrupted time series analysis was performed in Rouen, with adjustment on Le Havre in an ARMA(1,1) model with the precision of one week. This statistical analysis has the advantage of taking into account a possible seasonal effect. The primary outcome was the incidence of all coronary events and the secondary outcome was the variation in incidence of ST-segment elevation myocardial infraction (STEMI). In the 21 weeks preceding the fire, there were a mean of 62.0 ± 10.1 coronary events per week in the exposed town, non-significantly increasing to 70.6 ± 10.5 in the 14 weeks following the fire, with an estimated increase of +5.5 events/week (95% CI: −6.0 to +16.9, P = 0.36). The mean number of STEMI events per week in Rouen changed from 6.19 ± 2.96 before to 7.93 ± 3.65 after the fire, with a difference estimated at +1.8 events/week (95% CI: −0.5 to +4.1, P = 0.13) ( Fig. 1 ). Our study did not find a significant effect of the Lubrizol factory fire on the incidence of coronary events. Further studies are needed to investigate the impact of industrial accidents on coronary events.

Coronary artery calcium and cardiovascular disease prediction by scanner type: the multi-ethnic study of atherosclerosis

To evaluate the predictive value of coronary artery calcium (CAC) scoring methods across cardiac computed tomography (CT) scanner types. CAC was measured in participants from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of participants free of baseline cardiovascular disease (CVD), using either EBCT (electron beam CT) or MDCT (multidetector CT). The risks for incident coronary heart disease (CHD) and CVD events were compared for CAC scores per SD using Cox proportional hazards models with multivariable adjustment in 3,362 MESA participants with detectable CAC. Using the Agatston score, the hazard ratio (HR) and 95% confidence interval (CI) for CHD was 1.50 (1.27,1.78) for EBCT and 1.60 (1.37,1.87) for MDCT. Using volume and density scores, the HR for CHD was 2.14 (1.71,2.68) for volume and 0.61 (0.48,0.76) for density on EBCT and 1.73 (1.42,2.11) for volume and 0.88 (0.71,1.10) for density on MDCT. Similar results were seen for CVD risk and in analyses stratified by sex, body mass index (BMI), and age. The volume and density score model demonstrated higher areas under the curve (AUC) for CHD than the Agatston score with EBCT (0.702, 95% CI: 0.666,0.738 versus 0.677, 95% CI: 0.638,0.715, p<0.001) and MDCT (0.669, 95% CI: 0.632,0.705 versus 0.660, 95% CI: 0.622,0.697, p=0.216). The CAC volume and density scores provide better risk prediction than the Agatston score for CHD and CVD events, regardless of CT scanner type. CAC density was strongly and inversely associated with CHD risk. Both density and volume score prediction were stronger for EBCT than MDCT.

Risk of coronary stenosis after adjuvant radiotherapy for breast cancer

PurposeAdjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT.MethodsA cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence.ResultsA total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21–1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22–2.10), 1.38 (95% CI 1.07–1.78), and 2.43 (95% CI 1.33–4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT.ConclusionImplementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.