Risk Of Incident Myocardial Infarction Research Articles

Bone fracture is associated with incident myocardial infarction in long-term follow-up

BackgroundThe association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up.MethodsA total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997–2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.ResultsFrom 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83–3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02–1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34–1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23–2.63, P = 0.003).ConclusionsIt is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

Association between physical activity changes and incident myocardial infarction after ischemic stroke: a nationwide population-based study

BackgroundThe impact of changes in physical activity after ischemic stroke (IS) on the subsequent myocardial infarction (MI) risk is not fully understood. We aimed to investigate the effects of changes in physical activity on the risk of MI after acute IS using data from the Korean National Health Insurance Services Database.Methods224,764 patients newly diagnosed with IS between 2010 and 2016 who underwent two serial biannual health checkups were included. The participants were divided into four categories according to changes in their physical activity: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was a new diagnosis of incident MI. Multivariable Cox proportional models were used to assess the effects of changes in exercise habits on the risk of MI.ResultsAfter a median of 4.25 years of follow-up, 6,611 (2.94%) MI cases were observed. After adjusting for confounders, new exercisers and exercise maintainers were significantly associated with a lower risk of incident MI than persistent non-exercisers (aHR, 0.849; 95% CI, 0.792–0.911; P-value < 0.001; and aHR, 0.746; 95% CI, 0.696–0.801; P-value < 0.001, respectively). Effects were consistent across sexes, more pronounced in those > 65 years. Notably, any level of physical activity after stroke was associated with a reduced MI risk compared to no exercise.ConclusionsIn this nationwide cohort study, commencing or sustaining physical activity after an IS corresponded to a diminished likelihood of subsequent MI development. Advocating physical activity in ambulatory stroke survivors could potentially attenuate the prospective risk of MI.

Premorbid physical activity and prognosis after incident myocardial infarction: the Atherosclerosis Risk in Communities Study

High to moderate levels of physical activity (PA) are associated with low risk of incident cardiovascular disease. However, it is unclear whether the benefits of PA in midlife extend to cardiovascular health following myocardial infarction (MI) in later life. Among 1,111 ARIC participants with incident MI during ARIC follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA on average 11.9 (SD 6.9) years prior to incident MI (premorbid PA) was evaluated as the average score of PA between visit 1 (1987-89) and visit 3 (1993-95) using a modified Baecke questionnaire. Total and domain-specific PA (sport, non-sport leisure, and work PA) was analyzed for associations with composite and individual outcomes of mortality, recurrent MI, and stroke after index MI using multivariable Cox models. During a median follow-up of 4.6 (IQI 1.0-10.5) years after incident MI, 823 participants (74%) developed a composite outcome. The 10-year cumulative incidence of the composite outcome was lower in the highest, as compared to the lowest tertile of premorbid total PA (56% vs. 70%, respectively). This association remained statistically significant even after adjusting for potential confounders (adjusted hazard ratio [aHR] 0.80 [0.67-0.96] for the highest vs. lowest tertile). For individual outcomes, high premorbid total PA was associated with a low risk of recurrent MI (corresponding aHR 0.64 [0.44, 0.93]). When domain-specific PA was analyzed, similar results were seen for sport and work PA. The association was strongest in the first year following MI (e.g., aHR of composite outcome 0.66 [95% CI 0.47, 0.91] for the highest vs. lowest tertile of total PA). Premorbid PA was associated positively with post-MI cardiovascular health. Our results demonstrate the additional prognostic advantages of PA beyond reducing the risk of incident MI.

Co-exposure to multiple air pollutants, genetic susceptibility, and the risk of myocardial infarction onset: a cohort analysis of the UK Biobank participants.

The relationship between the long-term joint exposure to ambient air pollution and incidence of myocardial infarction (MI) and modification by genetic susceptibility remain inconclusive. We analysed 329 189 UK Biobank participants without MI at baseline. Exposure concentrations to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were obtained. Air pollution score assessing the joint exposure was calculated, and its association with MI was evaluated via Cox model under the P value aggregation framework. Genetic susceptibility to MI was evaluated by incorporating polygenic risk score (PRS) into models. Risk prediction models were also established. During a median follow-up of 13.4 years, 9993 participants developed MI. Per interquartile range increase of PM2.5, PM10, NO2, and NOx resulted in 74% [95% confidence intervals (CIs) 69%-79%], 67% (63%-72%), 46% (42%-49%), and 38% (35%-41%) higher risk of MI. Compared with the lowest quartile (Q1) of air pollution score, the multivariable adjusted hazard ratio (HR) (95%CIs) of Q4 (the highest cumulative air pollution) was 3.50 (3.29-3.72) for MI. Participants with the highest PRS and air pollution score possessed the highest risk of incident MI (HR = 4.88, 95%CIs 4.35-5.47). Integrating PRS, air pollution exposure, and traditional factors substantially improved risk prediction of MI. Long-term joint exposure to air pollutants including PM2.5, PM10, NO2, and NOx is substantially associated with increased risk of MI. Genetic susceptibility to MI strengthens such adverse joint association. Air pollutions together with genetic and traditional factors enhance the accuracy of MI risk prediction.

Cumulative incidence and risk factors of myocardial infarction during 21 years of follow-up: comparing two cohorts of middle-aged men born 30 years apart

Abstract Background The morbidity and mortality burden associated with coronary artery disease (CAD) has declined over the past decades which are believed to be attributable to reductions in the prevalence of major cardiovascular risk factors alongside with improvements in acute management of myocardial infarction (MI). Nevertheless, CAD remains one of the leading causes of death globally. Recent studies indicated that some major cardiovascular risk factors have been modified over time, with decreasing number of smokers and hypercholesterolemia and increasing rates of obesity and diabetes. This may have impact on the incidence of CAD. Therefore, further understanding of changes of major risk factors for CAD overtime is needed. Aim To study cumulative incidence and predictors of MI in two random general population samples consisting of middle-aged men born 30 years apart. Method The "Study of Men Born In 1913" and the "Study of Men Born In 1943" are two longitudinal cohort studies investigating cardiovascular risk factors and diseases, performed in the same geographic area and using the same methodology, with repeated examinations. Both cohorts were followed prospectively for 21 years from the 50 years of age. MI was defined as new onset of myocardial infarction, fatal or non-fatal. Results A total number of 1625 participants were included in the study. Men born in 1943 had a 34% lower risk of acute MI [HR 0.66 (0.50-0.88), p=0.0051] during follow-up as compared to men born in 1913. Both cohorts had similar risk factors and hypertension was associated with at least 2-fold higher risk for incident MI in men born in 1943 [HR 2.33 (95% CI 1.41 - 3.83)], p=0.0009 as compared to the risk in men born in 1913 [HR: 1.10 (0.74-1.62)]. Conclusion Despite declining incidence of MI the last five decades, risk profile of MI remained almost the same, and hypertension became an increasingly prominent risk factor to MI. Greater efforts should be dedicated in primary prevention in order to further reduce the risk of MI.

PO-05-167 THE BIDIRECTIONAL ASSOCIATION BETWEEN ATRIAL FIBRILLATION AND MYOCARDIAL INFARCTION IN THE FRAMINGHAM HEART STUDY

Atrial fibrillation (AF) and myocardial infarction (MI) are major contributors to disease burden. Studies suggest a bidirectional association between AF and MI. 1) To assess the bidirectional association between MI and AF, 2) to describe temporality between MI and AF among Framingham Heart Study participants with new-onset AF/MI, 3) to examine the association between interim/prevalent MI/AF and mortality among new-onset AF/MI cases. For aim 1, we included participants aged ≥45 years attending exams between 1960-2019. Multivariable-adjusted Cox proportional hazards models were used to calculate hazards ratios (HR) and 95% confidence intervals (CI) for the association between prevalent/interim MI/AF and incident AF/MI. Interim AF/MI were included as time-varying variables. For aims 2 and 3, we included all participants aged ≥45 years developing AF/MI from 1960-2019. In new-onset AF cases, we assessed percentages of prevalent MI, concurrent MI (diagnosed on the same day), and no MI, at time of AF diagnosis. Multivariable-adjusted HRs (95% CIs) were calculated for the association between prevalent/interim MI and mortality among participants with new-onset AF. We performed corresponding analyses for new-onset MI cases, using AF as exposure. In 10,334 participants free of MI at baseline (56% female, mean age 54±7 years), incidence rates of MI according to AF status are shown in table. The risk of incident MI was higher with interim compared to no AF (table). In 10,488 participants free of AF at baseline (55% female, mean age 54±7 years), incidence rates of AF according to MI status are displayed in table. The risk of incident AF was higher with prevalent and interim MI compared to no MI (table). In the 1,847 participants developing AF during 1960-2019 (46% female, mean age 75±11 years), 15% had prevalent MI, 2% had concurrent MI, and 84% had no MI, at time of AF diagnosis. In the 1,091 participants developing MI (42% female, mean age 70±11 years), 9% had prevalent AF, 3% had concurrent AF, and 89% had no AF, at time of MI diagnosis. In participants with new-onset AF or MI, prevalent and interim MI or AF were associated with significantly greater mortality compared to only AF or MI (table). The risk of incident AF was greater in participants with MI compared to no MI. The risk of incident MI was higher in participants with AF compared to no AF. Co-existing AF and MI were associated with a greater mortality compared to only AF or MI.Tabled 1(PO-05-167)Study SampleExposureOutcomeIncidence Rate per 1,000 person-years (95% CI)Hazards Ratio (95% CI)P-valueAF-free participants (N=10,488)Prevalent MIIncident AF23 (19-27)1.72 (1.41-2.11)<0.0001Interim MI50 (42-60)4.36 (3.51-5.42)<0.0001No MI8 (7-8)1.00 (ref)--MI-free participants (N=10,334)Prevalent AFIncident MI11 (8-15)1.33 (0.95-1.87)0.10Interim AF20 (16-26)2.75 (2.06-3.66)<0.0001No AF5 (4-5)1.00 (ref)--New-onset AF cases (N=1,847)Prevalent MIAll-cause mortality159 (139-180)1.36 (1.17-1.58)<0.0001Interim MI202 (161-252)2.25 (1.71-2.98)<0.0001No MI103 (97-109)1.00 (ref)--New-onset MI cases (N=1,091)Prevalent AFAll-cause mortality191 (153-236)1.60 (1.26-2.02)<0.0001Interim AF170 (147-192)2.53 (2.09-3.07)<0.0001No AF78 (72-84)1.00 (ref)-- Open table in a new tab

Association of Traumatic Injury and Incident Myocardial Infarction and Stroke: A Prospective Population-Based Cohort Study

Background: Several studies have linked traumatic injury and cardiovascular disease. However, few studies have investigated the associations between traumatic injury and cardiovascular disease subtypes. We aimed to prospectively examine the association between traumatic injury and the risk of incident myocardial infarction (MI) and stroke. Methods: This study was based on a prospective cohort study that included 13,973 patients who had been hospitalized for traumatic injuries from 1980 to 2020. We randomly selected 4 uninjured participants from the cohort study for each patient as controls matched by age (±3 years) and sex. All participants were free of MI and stroke at enrollment. Cox regression was used to examine the association between traumatic injury and incident MI and stroke. Results: During a median follow-up period of 13.5 years, 1032 cases of MI and 4068 cases of stroke were recorded. After multivariable adjustment, relative to controls, patients with severe injury had the highest hazard ratio (HR) for MI (HR = 1.93; 95% CI: 1.26–2.96) and stroke (HR = 1.60; 95% CI: 1.25–2.05). The HRs of MI and stroke were 0.97 (0.81–1.17) and 1.11 (1.02–1.21) for patients with mild injury and 1.28 (0.97–1.69) and 1.22 (1.06 to 1.41) for patients with moderate injury. Additionally, patients with older age at injury and chest injury had a higher HR for MI and stroke (p-interaction &lt; 0.05). Conclusions: Traumatic injury appears to be associated with an increased risk of incident MI and stroke. Therefore, early screening and prevention of MI and stroke following a traumatic injury are needed.

Adipose tissue n-3/n-6 fatty acids ratios versus n-3 fatty acids fractions as predictors of myocardial infarction

Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions. Subcutaneous adipose tissue biopsies were obtained in a random sample (n=3,500) of the Diet, Cancer and Health cohort (n=57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design. A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA+DHA, EPA, EPA/AA, DHA/AA and (EPA+DPA+DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel's C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA+DHA)/AA and (EPA+DPA+DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake. Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies.

Association of Joint Genetic and Social Environmental Risks With Incident Myocardial Infarction: Results From the Health and Retirement Study.

Background Myocardial infarction (MI) is a significant clinical and public health problem worldwide. However, little research has assessed the interplay between genetic susceptibility and social environment in the development of MI. Methods and Results Data were from the HRS(Health and Retirement Study). The polygenic risk score and polysocial score for MI were classified as low, intermediate, and high. Using Cox regression models, we assessed the race-specific association of polygenic score and polysocial score with MI and examined the association between polysocial score and MI in each polygenic risk score category. We also examined the joint effect of genetic (low, intermediate, and high) and social environmental risks (low/intermediate, high) on MI. A total of 612 Black and 4795 White adults aged ≥65 years initially free of MI were included. We found a risk gradient of MI across the polygenic risk score and polysocial score among White participants; no significant risk gradient across the polygenic risk score was found among Black participants. A disadvantaged social environment was associated with a higher risk of incident MI among older White adults with intermediate and high genetic risk but not those with low genetic risk. We revealed the joint effect of genetics and social environment in the development of MI among White participants. Conclusions Living in a favorable social environment is particularly important for people with intermediate and high genetic risk for MI. It is critical to developing tailored interventions to improve social environment for disease prevention, especially among adults with a relatively high genetic risk.

Abstract P435: Proton Pump Inhibitor Use and Risk of Incident Primary Cardiovascular Disease: A Systematic Review and Meta-Analysis

Background: The risk of secondary cardiovascular events associated with proton pump inhibitor (PPI) use and their interaction with thienopyridine antiplatelets such as clopidogrel is well established. Recent evidence from in-vitro and animal studies suggests PPIs may impact cardiovascular disease (CVD) irrespective of antiplatelet use. However, whether PPI use is associated with primary cardiovascular events in humans remains uncertain. Methods: Systematic searches were conducted in the MEDLINE and EMBASE databases from their inception to September 2022. Inclusion criteria included studies that examined participants free from cardiovascular disease at baseline who were followed over time to assess any of the following outcomes according to PPI use: incident myocardial infarction (MI), incident ischemic stroke (IS), or CVD mortality. Hazard ratios (HR) and their 95% confidence intervals (CI) were abstracted, combined estimates and heterogeneity (I 2 ) were calculated using the random-effects model in RevMan 5.4 software. Results: A total of 15 observational studies met the inclusion criteria, 2,272,479 participants were studied for MI, 2,689,943 for IS, and 1,591,428 for CVD mortality. The mean age of participants ranged from 49.3 to 82.2 years. Compared to non-use, PPI use was associated with 30% higher risk of incident MI (HR: 1.30, 95%CI: 1.10-1.53, I 2 =91%) and 15% higher risk of CVD mortality (HR: 1.15, 95%CI: 1.05-1.26, I 2 =56%). However, there was no statistically significant association with incident IS (HR: 1.05, 95%CI: 0.91-1.22, I 2 =96%). Conclusion: The meta-analysis results from published studies suggests PPI use is associated with higher risk of incident MI and CVD mortality. However, these findings should be interpreted with caution given the considerable heterogeneity among published studies and the possibility of residual confounding. More studies are needed to address these limitations and determine the validity of these associations.

Prevalence and incidence of cardiovascular and renal diseases in type 1 compared with type 2 diabetes: A nationwide French observational study of hospitalized patients

BackgroundType 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) increase risks of cardiovascular (CV) and renal disease compared with diabetes-free populations. There are only a few studies comparing T1DM and T2DM for the relative risk of these clinical events. MethodsAll adult patients hospitalized in French hospitals in 2013 with at least 5 years of follow-up were identified and categorized by their diabetes status. A total of 50,623 patients with T1DM (age 61.4 ± 18.6, 53% male) and 425,207 patients with T2DM (age 68.6 ± 14.3, 55% male) were followed over a median period of 5.3 years (interquartile range: 2.8 - 5.8 years). Prevalence and event rates of myocardial infarction (MI), heart failure (HF), ischemic stroke, chronic kidney disease (CKD), all-cause death and CV death were assessed with age stratification of 10-year intervals. For clinical events during follow-up, we report hazard ratios (HRs) in T1DM relative to T2DM. ResultsThe age and sex-adjusted prevalence of CV diseases was higher in T2DM for ages above 40 years whereas the prevalence of CKD was more common in T1DM between ages 18 and 70 years. During 2,033,239 person-years of follow-up, age and sex-adjusted HR event rates comparing T1DM, versus T2DM as reference, showed that MI and HF relative risks were increased above 60 years (1.2 and 1.4 -fold). HR of ischemic stroke did not markedly differ between T1DM and T2DM. Risk of incident CKD was 2.4-fold higher in T1DM above 60 years. All-cause death HR risk was 1.1-fold higher in T1DM after 60 years and the CV death risk was 1.15-fold higher in T1DM between 60 and 69 years compared to T2DM. ConclusionsAlthough the crude prevalent burden of CV diseases may be lower in T1DM than in T2DM, patients with T1DM may have a higher risk of incident MI, HF, all-cause death and CV death above 60 years of age, highlighting the need for improved prevention in this population.

Machine Learning to Understand Genetic and Clinical Factors Associated With the Pulse Waveform Dicrotic Notch.

Absence of a dicrotic notch on finger photoplethysmography is an easily ascertainable and inexpensive trait that has been associated with age and prevalent cardiovascular disease. However, the trait exists along a continuum, and little is known about its genetic underpinnings or prognostic value for incident cardiovascular disease. In 169 787 participants in the UK Biobank, we identified absent dicrotic notch on photoplethysmography and created a novel continuous trait reflecting notch smoothness using machine learning. Next, we determined the heritability, genetic basis, polygenic risk, and clinical relations for the binary absent notch trait and the newly derived continuous notch smoothness trait. Heritability of the continuous notch smoothness trait was 7.5%, compared with 5.6% for the binary absent notch trait. A genome-wide association study of notch smoothness identified 15 significant loci, implicating genes including NT5C2 (P=1.2×10-26), IGFBP3 (P=4.8×10-18), and PHACTR1 (P=1.4×10-13), compared with 6 loci for the binary absent notch trait. Notch smoothness stratified risk of incident myocardial infarction or coronary artery disease, stroke, heart failure, and aortic stenosis. A polygenic risk score for notch smoothness was associated with incident cardiovascular disease and all-cause death in UK Biobank participants without available photoplethysmography data. We found that a machine learning derived continuous trait reflecting dicrotic notch smoothness on photoplethysmography was heritable and associated with genes involved in vascular stiffness. Greater notch smoothness was associated with greater risk of incident cardiovascular disease. Raw digital phenotyping may identify individuals at risk for disease via specific genetic pathways.

G Protein-Coupled Receptor 15 Expression Is Associated with Myocardial Infarction.

Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case−control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10−7). GPR15 expression correlated with intima-media thickness (β = 0.8498, p = 0.111), C-reactive protein (β = 0.2238, p = 0.0052), ejection fraction (β = −0.9991, p = 0.0281) and smoking (β = 0.7259, p = 2.79 × 10−10). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10−5) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10−6/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.

Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults

ObjectiveTo examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.MethodsCompeting risk regression was used to estimate associations of...

Abstract 12084: Premorbid Physical Activity and Prognosis After Incident Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Physical activity (PA) is associated with a reduced risk of mortality and cardiovascular disease in the general population. However, it is unclear whether PA level in midlife impacts prognosis after myocardial infarction (MI) in later life. Methods: In 1,115 ARIC participants with incident non-fatal MI during ARIC follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA prior to incident MI (premorbid PA) was evaluated at visit 1 (1987-89) and visit 3 (1993-95) using a modified Baecke questionnaire; we studied the cumulative PA index scores across these two visits. Total and domain-specific PA (sport, leisure time, and work PA) were analyzed for their associations with mortality, recurrent MI, stroke, and heart failure after MI using multivariable Cox models. Elapsed time between visit 3 and incident MI was on average 11.9 (SD 6.9) years. Results: During a median follow-up of 2.0 [IQI 0.03-8.0] years after incident MI, 914 participants (82%) developed a composite outcome. The 8-year cumulative incidence of composite outcome was lower in the highest tertile of premorbid total PA than the lowest tertile (62% vs. 72%, respectively) ( Figure ). When adjusting for MI risk factors, the association was not significant. However, for individual outcomes, higher premorbid total PA was associated with a lower risk of recurrent MI (adjusted hazard ratio [HR] 0.66 [95% CI 0.45, 0.96] for the highest vs. lowest tertile). Results were similar for sport and work PA but not leisure time PA. When we focused on short-term prognosis within one year after MI, both higher total PA and sport PA were associated with lower mortality (HR 0.62 [95% CI 0.43, 0.90] and 0.62 [0.44, 0.89], respectively). Conclusions: Greater premorbid PA was associated with better prognosis after MI occurrence, both short-term and long-term post-MI. Our results demonstrate additional prognostic advantage of PA beyond reducing the risk of incident MI.

Abstract 10103: Polygenic Scores and Longitudinal Trajectories of Cardiometabolic Phenotypes

Introduction: Genetic predisposition via polygenic scores (PGS) is strongly associated with single measurements of systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C), but it is unclear how PGS are associated with their longitudinal trajectories and how these trajectories are associated with risk of coronary heart disease (CHD). Hypothesis: PGS are associated with classes of longitudinal trajectories, and these trajectories are associated with CHD. Methods: Analyses were conducted in 8,453 white participants from the Atherosclerosis Risk in Communities study. SBP and LDL-C measurements were adjusted for medication use. Latent class models were used to group participants into longitudinal trajectory classes based on SBP and LDL-C values from 3-5 visits over up to 27 years. PGS were created by multiplying publicly available weights with participant genotype dosages. The association between PGS and trajectory classes for SBP and LDL-C was examined using logistic regression. We then examined the association of trajectory classes with incident myocardial infarction (MI) and CHD using cox proportional hazard models. Results: Participants were assigned to 4 classes of SBP and 2 classes of LDL-C trajectories ( Figure ). The SBP PGS was significantly associated with SBP classes 2 (OR = 1.28 per standard deviation change in the PGS, P = 4.8E-7) and 4 (OR = 1.7, P &lt; 2E-16) relative to class 3, and with class 4 relative to class 2 (OR= 1.3, P = 2.0E-6). The LDL-C PGS was significantly associated with class 2 (OR = 1.63, P &lt; 2E-16). There were 147 CHD and 102 MI events during 7 additional years of follow up. SBP class 2 and LDL-C class 2 were significantly associated with greater risk of incident MI. Conclusions: Our results highlight longitudinal trajectory classes as a tool for contextualizing the genomics of cardiometabolic phenotypes and the association of these phenotypes with CHD.

Association of Cardiovascular Health Score Trajectory With Incident Myocardial Infarction in Hypertensive Patients

The association between changes in cardiovascular health score (CHS) over time and myocardial infarction (MI) risk in hypertensive patients remains unclear. This was a prospective study comprising 17 374 hypertensive patients from the Kailuan study cohort who underwent 3 surveys and were identified to be free of MI, stroke, or cancer from 2006 to 2010. CHS consisted of 7 cardiovascular health metrics (plasma glucose, total cholesterol, blood pressure, smoking, body mass index, physical activity, salt intake), ranging from 0 (worst) to 13 (best) in the study. CHS trajectories were developed during 2006 to 2010 to predict the MI risk from 2010 to 2020. Additionally, the Cox proportional hazard model was established to calculate the hazard ratio and 95% CI of incident MI in different trajectory groups. This study identified the 5 CHS trajectories from 2006 to 2010: low-stable (n=1161; range, 4.7-4.5), moderate-decreasing (n=3928; decreased from 6.9 to 6.0), moderate-increasing (n=1014; increased from 5.6 to 7.8), high-stable I (n=7940; range, 8.1-8.2), and high-stable II (n=3331; range, 9.2-9.7). During the median follow-up of 10.04 years, 288 incident MI cases were identified. After adjusting for potential confounders, compared with low-stable group, the hazard ratio and 95% CI of MI were 0.24 (0.15-0.40) for high-stable II, 0.36 (0.24-0.54) for high-stable I, 0.46 (0.25-0.83) for moderate-increasing, and 0.61 (0.41-0.90) for moderate-decreasing, respectively. In hypertensive patients, high-stable CHS or improvement in CHS is associated with a lower risk of incident MI, when compared with low-stable CHS trajectory over time.

Antiplatelet therapy and risk of adverse cardiovascular events in peripheral artery disease

Abstract Background Antiplatelet therapy has been shown to reduce adverse cardiovascular (CV) events in patients with PAD, but despite the well-established medication benefit, large-scale epidemiological data evaluating antiplatelet agent of choice with low bleeding risk and high antithrombotic effect is sparse. Purpose We explored Danish healthcare registers to examine guideline-recommended antiplatelet therapy and associated risk of adverse CV outcomes in patients with PAD. Methods All patients with a first-time diagnosis of PAD between January 1, 1997 and December 31, 2016 were identified. Patients alive six months after diagnosis were divided into four treatment groups: aspirin, clopidogrel, dual therapy (DAPT), and no antiplatelet therapy. Logistic regression models were used to estimate 1-year risk of myocardial infarction (MI), stroke, CV death, all-cause mortality, and gastrointestinal (GI) bleeding. Results We identified a total of 85,771 PAD patients [median age 70.6 (IQR 63–77 years), 52% male]. The results suggest that compared to no antiplatelet therapy, use of clopidogrel alone significantly decreased 1-year risk of incident MI, stroke, CV death and all-cause mortality with odds ratios 0.56 (CI 0.46–0.68), 0.69 (CI 0.59–0.81), 0.72 (CI 0.56–0.94), and 0.79 (CI 0.65–0.97) respectively. Likewise, aspirin monotherapy was associated with only a marginal reduction in 1-year risk of stroke by 11% and all-cause mortality by 7%. Odds ratios for GI bleeding were estimated to be 1.18 (CI 1.04–1.34), 1.34 (CI 0.94–1.91), and 1.54 (CI 1.05–2.26) for aspirin, clopidogrel, and DAPT groups, respectively. Conclusion In this nationwide study, clopidogrel is associated with significantly reduced risk of MI, stroke, CV death and all-cause mortality with low risk of bleeding and appears to support clopidogrel as antiplatelet agent of choice for CV risk reduction in patients with PAD. Funding Acknowledgement Type of funding sources: None.

The relationship between thyroid dysfunction, cardiovascular morbidity and mortality in type 2 diabetes: The Fremantle Diabetes Study Phase II

AimsIt is uncertain whether subclinical thyroid dysfunction is associated with cardiovascular disease (CVD) events and mortality in people with type 2 diabetes. The aim of this study was to determine whether undetected thyroid disease increases the risk of incident CVD and death in type 2 diabetes.MethodsOne thousand two hundred fifty participants with type 2 diabetes (mean age 65.3 years, 56.5% males, median diabetes duration 8.0 years) without known thyroid disease and not taking medications known to affect thyroid function were categorised, based on baseline serum free thyroxine (FT4) and thyrotropin (TSH) concentrations, as euthyroid, overt hypothyroid (increased TSH, low FT4), subclinical hypothyroid (increased TSH, normal FT4), overt thyrotoxic (decreased TSH, raised FT4) or subclinical thyrotoxic (decreased TSH, normal FT4). Incident myocardial infarction, incident stroke, all-cause and cardiovascular mortality were ascertained during a mean 6.2–6.7 years of follow-up.ResultsMost participants with newly-detected thyroid dysfunction had subclinical hypothyroidism (77.2%) while overt/subclinical thyrotoxicosis was infrequent. Compared to participants with TSH 0.34–2.9 mU/L, those with TSH > 5.1 mU/L were not at increased risk of incident myocardial infarction (adjusted hazard ratio (95% confidence limits) 1.77 (0.71, 2.87)), incident stroke (1.66 (0.58, 4.78)), all-cause mortality (0.78 (0.44, 1.37)) or cardiovascular mortality (1.16 (0.38, 3.58)). Independent baseline associates of subclinical hypothyroidism included estimated glomerular filtration rate and systolic blood pressure.ConclusionsSubclinical hypothyroidism was not independently associated with CVD events or mortality in community-dwelling people with type 2 diabetes despite its associations with CVD risk factors, questioning strategies to identify and/or treat mild thyroid dysfunction outside usual care.

Plasma epoxyeicosatrienoic acids and diabetes-related cardiovascular disease: The cardiovascular health study.

SummaryBackgroundEpoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that may impact atherosclerosis, and animal experimental studies suggest EETs protect cardiac function. Plasma EETs are mostly esterified to phospholipids and part of an active pool. To address the limited information about EETs and CVD in humans, we conducted a prospective study of total plasma EETs (free + esterified) and diabetes-related CVD in the Cardiovascular Health Study (CHS).MethodsWe measured 4 EET species and their metabolites, dihydroxyepoxyeicosatrienoic acids (DHETs), in plasma samples from 892 CHS participants with type 2 diabetes. We determined the association of EETs and DHETs with incident myocardial infarction (MI) and ischemic stroke using Cox regression.FindingsDuring follow-up (median 7.5 years), we identified 150 MI and 134 ischemic strokes. In primary, multivariable analyses, elevated levels of each EET species were associated with non-significant lower risk of incident MI (for example, hazard ratio for 1 SD higher 14,15-EET: 0.86, 95% CI: 0.72–1.02; p=0.08). The EETs-MI associations became significant in analyses further adjusted for DHETs (hazard ratio for 1 SD higher 14,15-EET adjusted for 14,15-DHET: 0.76, 95% CI: 0.63–0.91; p=0.004). Elevated EET levels were associated with higher risk of ischemic stroke in primary but not secondary analyses. Three DHET species were associated with higher risk of ischemic stroke in all analyses.InterpretationFindings from this prospective study complement the extensive studies in animal models showing EETs protect cardiac function and provide new information in humans. Replication is needed to confirm the associations.FundingUS National Institutes of Health.