Risk Of Incident Myocardial Infarction Research Articles

Allopurinol reduces the risk of myocardial infarction (MI) in the elderly: a study of Medicare claims.

BackgroundPrevious observational studies that have examined the association of allopurinol with myocardial infarction (MI) have provided contradictory results. One study showed that allopurinol reduced the risk, while another study showed an increased risk with allopurinol. Therefore, our objective was to assess whether allopurinol use is associated with a reduction in the risk of MI in the elderly.MethodWe used the 2006–2012 5 % random sample of Medicare beneficiaries to study the association of new allopurinol initiation and the risk of incident MI in a cohort study. Multivariable-adjusted Cox regression models adjusted for age, gender, race, and Charlson index, in addition to various cardio-protective medications (beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, diuretics, statins). We calculated hazard ratios (HRs) with 95 % confidence intervals (CIs). Sensitivity analyses adjusted for coronary artery disease (CAD) risk factors, including hypertension, hyperlipidemia, diabetes, and smoking.ResultsOf the 29,298 episodes of incident allopurinol use, 1544 were associated with incident MI (5.3 % episodes). Allopurinol use was associated with reduced hazards of MI, with a HR of 0.85 (95 % CI, 0.77 to 0.95). Compared to no allopurinol use, longer durations of allopurinol use were associated with a lower HR of MI: 1–180 days, 0.98 (95 % CI, 0.84 to 1.14); 181 days to 2 years, 0.83 (95 % CI, 0.72 to 0.95); and >2 years, 0.70 (95 % CI, 0.56 to 0.88). Other factors associated with a higher hazard of MI were: age 75 to <85 years and ≥85 years, male gender, higher Charlson index score, and the use of an ACE inhibitor. Adjustment for CAD risk factors confirmed these findings.ConclusionIncident allopurinol use was associated with a reduction in the risk of incident MI in the elderly. Longer durations of allopurinol use reduced the risk of incident MI incrementally. Future studies should assess the underlying mechanisms for MI prevention and assess the risk-benefit ratio for allopurinol use.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1111-1) contains supplementary material, which is available to authorized users.

Lifelong Gender Gap in Risk of Incident Myocardial Infarction

It is not clear to what extent the higher incidence of coronary heart disease (CHD) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex. Moreover, the increase in risk of CHD in postmenopausal women, possibly hormone related, may eventually eliminate the sex contrast in risk, but age-specific risk estimates are scarce. To quantify the difference in risk of incident myocardial infarction (MI) between men and women. Population-based prospective study from Tromsø, Norway, comprising 33 997 individuals (51% women). Median follow-up time during ages 35 to 102 years was 17.6 years. Incidence rates (IRs) and incidence rate ratios (IRRs, relative risk) of MI were calculated in Poisson regression analysis of person-years at risk. The data analysis was performed in November 2015. Sex, age, birth cohort, serum lipid levels, blood pressure, lifestyle factors, diabetes. Incident MI. A total of 2793 individuals (886 women) received a diagnosis of MI during follow-up in the period 1979 through 2012. The IR increased with age in both sexes, with lower rates for women until age 95 years. Adjusted for age and birth cohort, the overall IRR for men vs women was 2.72 (95% CI, 2.50-2.96). Adjustment for high-density lipoprotein cholesterol and total cholesterol levels had the strongest impact on the risk estimate for sex, followed by diastolic blood pressure and smoking. However, the sex difference remained substantial even after adjustment for these factors (IRR, 2.07; 95% CI, 1.89-2.26). Men had higher risk throughout life, but the IRRs decreased with age (3.64 [95% CI, 2.85-4.65], 2.00 [95% CI, 1.76-2.28], and 1.66 [95% CI, 1.42-1.95] for age groups 35-54, 55-74, and 75-94 years, respectively). Adjustment for systolic blood pressure, diabetes, body mass index, and physical activity had no notable impact. The observed sex contrast in risk of MI cannot be explained by differences in established CHD risk factors. The gender gap persisted throughout life but declined with age as a result of a more pronounced flattening of risk level changes in middle-aged men. The minor changes in IRs when moving from premenopausal to postmenopausal age in women make it unlikely that changes in female hormone levels influence the risk of MI.

Atrial fibrillation is associated with an increased risk of myocardial infarction: Insights from a meta-analysis

Background and aimsThe presence of atrial fibrillation (AF) markedly increases the risk of stroke and mortality in patients. Whether AF is a risk factor for myocardial infarction (MI) is discrepant from current studies. The aim of this meta-analysis was to ascertain the association of AF with incident MI. MethodsStudies were identified through PubMed, CENTRAL, EMBASE, reviews and reference lists of relevant papers. Results of the MI outcome were presented as hazard ratio (HR) and 95% confidence interval (CI). Statistical analyses were performed with Stata 12.0 (Stata Corp LP, College Station, Texas, USA). ResultsTwelve studies, with a total of 169,306 patients, were included in the analysis. AF was associated with a 47% increased risk of MI (HR:1.47; 95% CI: 1.21–1.80; p = 0.000; I2 = 84.1%), while in patients free of coronary heart disease at baseline the risk could be increased by 71% (HR:1.71; 95% CI: 1.36–2.14; p = 0.000; I2 = 83.1%). Moreover, patients with AF had higher MI risk in the studies with lower mean age (<60 years) (HR:1.66; 95% CI: 1.26–2.20; p = 0.000; I2 = 82.9%) than in the studies with higher mean age (≥60 years) (HR:1.35; 95% CI: 1.00–1.82; p = 0.000; I2 = 84.9%). Sex difference also existed, and the association between AF and MI was stronger in women (HR:2.02; 95% CI: 1.60–2.56; p = 0.017; I2 = 61.0%) than in men (HR:1.44; 95% CI: 1.13–1.84; p = 0.000; I2 = 76.1%). ConclusionsAF is associated with an increased risk of incident MI, especially in patients free of coronary heart disease at baseline, young patients and women. The findings need confirmation in well-designed observational trials.

Ambient Air Pollution Is Associated With the Severity of Coronary Atherosclerosis and Incident Myocardial Infarction in Patients Undergoing Elective Cardiac Evaluation.

BackgroundThe effect of air pollution exposure on atherosclerosis severity or incident clinical events in patients with coronary artery disease is not known.Methods and ResultsWe conducted a prospective longitudinal cohort study of 6575 Ohio residents undergoing elective diagnostic coronary angiography. Multinomial regression and Cox proportional hazards models were used to assess the relationship between exposure to fine particulate matter <2.5 μm in diameter (PM 2.5) and nitrogen dioxide on coronary artery disease severity at baseline and risk of myocardial infarction, stroke, or all‐cause mortality over 3 years of follow‐up. Among participants with coronary artery disease, exposure to PM 2.5 levels was associated with increased likelihood of having coronary atherosclerosis that was mild (odds ratio 1.43, 95% CI 1.11–1.83, P=0.005) and severe (odds ratio 1.63, 95% CI 1.26–2.11, P<0.0001), with the effect on severe coronary artery disease being significantly increased compared with mild disease (P trend=0.03). Exposure to higher PM 2.5 levels was also significantly associated with increased risk of incident myocardial infarction (hazard ratio 1.33, 95% CI 1.02–1.73, P=0.03) but not stroke or all‐cause mortality. The association of PM 2.5 with incident myocardial infarction was not affected after adjustment for Framingham Adult Treatment Panel III (ATP III) risk score or statin therapy. In comparison, there were no significant associations between nitrogen dioxide levels and all‐cause mortality or risk of stroke after adjustment for Framingham ATP III risk score.ConclusionsExposure to PM 2.5 increased the likelihood of having severe coronary artery disease and the risk of incident myocardial infarction among patients undergoing elective cardiac evaluation. These results suggest that ambient air pollution exposure may be a modifiable risk factor for risk of myocardial infarction in a highly susceptible patient population.

Dietary intake and adipose tissue content of α-linolenic acid and risk of myocardial infarction: a Danish cohort study1–3

Background: Intake of the plant-derived ω-3 (n–3) fatty acid α-linolenic acid (ALA, 18:3; n–3) may reduce coronary heart disease (CHD) risk, but the results of previous studies have been inconsistent.Objective: We aimed to investigate the association between dietary intake of ALA, adipose tissue content of ALA, and risk of incident myocardial infarction (MI).Design: A total of 57,053 participants, aged 50–64 y, were enrolled in the prospective Danish cohort study Diet, Cancer and Health between 1993 and 1997. Dietary intake of ALA was assessed with the use of a validated semiquantitative food-frequency questionnaire in the full cohort, whereas the adipose tissue content of ALA was determined with the use of gas chromatography in all incident MI cases and in a random sex-stratified sample of the total cohort (n = 3500).Results: During a median of 17 y of follow-up, we identified 2177 male and 912 female cases of MI. After appropriate exclusions, we included 2124 men and 854 women for analyses of dietary intake of ALA, whereas 1994 men and 770 women were included in the analysis of the adipose tissue content of ALA. In multivariate analyses that were conducted with the use of restricted cubic splines and adjusted for established CHD risk factors, weak positive associations in men and weak U-shaped associations in women were shown between both dietary intake and the adipose tissue content of ALA and risk of MI, but these associations were not statistically significant. Additional adjustments for dietary factors did not influence the observed associations numerically.Conclusion: This study suggests that ALA has no appreciable association with risk of incident MI in either men or women.

Usefulness of Plasma Matrix Metalloproteinase-3 Levels to Predict Myocardial Infarction in Men With and Without Acute Coronary Syndrome

Matrix metalloproteinase-3 (MMP-3), or stromelysin-1, is a matrix metalloproteinase which is expressed in atherosclerotic plaques and which has been implicated in the pathogenesis of acute coronary syndrome (ACS). Functional polymorphisms in the promoter region of the human MMP-3 gene resulting in an increased expression of MMP-3 have been shown to predict the risk of incident myocardial infarction (MI). However, there have been no studies that have specifically examined the utility of baseline plasma MMP-3 levels for the prediction of long-term MI. In this study, baseline plasma MMP-3 levels were measured in 355 male patients who were referred for coronary angiography and followed prospectively for the development of enzymatically confirmed MI out to 5years. After adjustment for a variety of baseline clinical, angiographic, and laboratory parameters, plasma MMP-3 levels were an independent predictor of MI at 5years (hazards ratio 1.42, 95% CI 1.13 to 1.79; p= 0.0023). Furthermore, in 5 additional multivariate models that included a variety of contemporary biomarkers associated with adverse outcomes and MI, MMP-3 remained an independent predictor of MI at 5years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with ACS. In conclusion, elevated levels of MMP-3 are associated with an increased risk of long-term MI in patients with and without ACS referred for coronary angiography. Furthermore, this association is independent of a variety of clinical, angiographic, laboratory variables, including biomarkers with established prognostic efficacy for the prediction of MI.

Recurrent vascular events in lacunar stroke patients with metabolic syndrome and/or diabetes.

We used a prospective clinical trial to examine the risks conferred by metabolic syndrome (METS) and diabetes mellitus (DM) to recurrent strokes in the Secondary Prevention of Small Subcortical Strokes (SPS3) study cohort. The SPS3 trial enrolled 3,020 patients with lacunar strokes. Participants were stratified into groups of METS only, DM only, both, or neither using American Heart Association/National Heart, Lung, and Blood Institute and World Health Organization guidelines. Annualized event rates of strokes, myocardial infarction (MI), and all-cause mortality were calculated, and hazard ratios (HRs) referencing the “neither” group were computed, controlling for significantly associated baseline characteristics. Among 2,999 participants, 25% had METS only, 6% had DM only, 32% had both conditions, and 37%had neither. Over a median of 3.8 years of follow-up, there were 274 recurrent strokes (240 ischemic, 34 hemorrhagic) and 74 MIs; among the 240 ischemic strokes, 134 (56%) were lacunar. The rates of any recurrent stroke (HR 1.7, 95% confidence interval [CI] 1.3–2.3) or lacunar stroke (HR 2.4, 95% CI 1.5–3.7) were significantly higher for those with concurrent METS and DM compared with those who had neither. Risk of incident MI was higher in participants with DM (HR 2.8, 95% CI 1.1–7.0) or concurrent DM and METS (HR 2.6, 95% CI 1.4–4.9). METS and DM were significant comorbid conditions in lacunar stroke patients and they were associated with stroke recurrence. In patients with lacunar infarcts, a vigilant approach to prevent development of DM in those with METS may be a potential strategy to reduce recurrent strokes.

Association Between Glycosylated Hemoglobin and Cardiovascular Events and Mortality in Older Adults without Diabetes Mellitus in the General Population: The Leiden 85-Plus Study.

To examine the association between glycosylated hemoglobin (HbA1c) and incident cardiovascular disease and mortality in 85-year-old individuals without diabetes mellitus from the general population. Population-based prospective follow-up study. General population. Individuals without known diabetes mellitus (N=445, n=291 female). HbA1c levels were categorized into three groups (<5.0% (31mmol/mol), 5.0-5.7% (31-39mmol/mol; reference), 5.7-6.5% (39-48mmol/mol)). At baseline, a history of myocardial infarction (MI) was more prevalent in subjects in the highest HbA1c group (18%) than in the reference group (7%) (P=.001). Prospectively, those with the highest level of HbA1c at baseline had a risk of incident MI during the 5-year follow-up that was 3.6 (95% confidence interval=1.5-8.3) times as great as that of the reference group. No association was found between HbA1c level and incident stroke, cardiovascular mortality, or all-cause mortality. In individuals aged 85 and older without diabetes mellitus, higher HbA1c is associated with greater risk of MI but not with stroke and mortality.

Atrial Fibrillation and Risk of ST-Segment-Elevation Versus Non-ST-Segment-Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study.

It has recently been reported that atrial fibrillation (AF) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association is currently unknown. Further study of the relationship of AF with the type of MI (ST-segment-elevation MI [STEMI] versus non-ST-segment-elevation MI [NSTEMI]) might shed light on the potential mechanisms. We examined the association between AF and incident MI in 14 462 participants (mean age, 54 years; 56% women; 26% blacks) from the Atherosclerosis Risk in Communities (ARIC) study who were free of coronary heart disease at baseline (1987-1989) with follow-up through December 31, 2010. AF cases were identified from study visit ECGs and by review of hospital discharge records. Incident MI and its types were ascertained by an independent adjudication committee. Over a median follow-up of 21.6 years, 1374 MI events occurred (829 NSTEMIs, 249 STEMIs, 296 unclassifiable MIs). In a multivariable-adjusted model, AF (n=1545) as a time-varying variable was associated with a 63% increased risk of MI (hazard ratio,1.63; 95% confidence interval, 1.32-2.02). However, AF was associated with NSTEMI (hazard ratio, 1.80; 95% confidence interval, 1.39-2.31) but not STEMI (hazard ratio, 0.49; 95% confidence interval, 0.18-1.34; P for hazard ratio comparison=0.004). Combining the unclassifiable MI group with either STEMI or NSTEMI did not change this conclusion. The association between AF and MI, total and NSTEMI, was stronger in women than in men (P for interaction <0.01 for both). AF is associated with an increased risk of incident MI, especially in women. However, this association is limited to NSTEMI.

Atrial Fibrillation and the Risk of Myocardial Infarction

Importance Myocardial infarction (MI) is an established risk factor for atrial fibrillation (AF). However, the extent to which AF is a risk factor for MI has not been investigated. Objective To examine the risk of incident MI associated with AF. Design, Setting, and Participants A prospective cohort of 23 928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, with follow-up through December 2009. Main Outcomes and Measures Expert-adjudicated total MI events (fatal and nonfatal). Results Over 6.9 years of follow-up (median 4.5 years), 648 incident MI events occurred. In a sociodemographic-adjusted model, AF was associated with about 2-fold increased risk of MI (hazard ratio [HR], 1.96 [95% CI, 1.52-2.52]). This association remained significant (HR, 1.70 [95% CI, 1.26-2.30]) after further adjustment for total cholesterol, high-density lipoprotein cholesterol, smoking status, systolic blood pressure, blood pressure–lowering drugs, body mass index, diabetes, warfarin use, aspirin use, statin use, history of stroke and vascular disease, estimated glomerular filtration rate, albumin to creatinine ratio, and C-reactive protein level. In subgroup analysis, the risk of MI associated with AF was significantly higher in women (HR, 2.16 [95% CI, 1.41-3.31]) than in men (HR, 1.39 [95% CI, 0.91-2.10]) and in blacks (HR, 2.53 [95% CI, 1.67-3.86]) than in whites (HR, 1.26 [95% CI, 0.83-1.93]); for interactions, P = .03 and P = .02, respectively. On the other hand, there were no significant differences in the risk of MI associated with AF in older (≥75 years) vs younger ( P = .44. Conclusions and Relevance AF is independently associated with an increased risk of incident MI, especially in women and blacks. These findings add to the growing concerns of the seriousness of AF as a public health burden: in addition to being a well-known risk factor for stroke, AF is also associated with increased risk of MI.

A genetic risk score of 45 coronary artery disease risk variants associates with increased risk of myocardial infarction in 6041 Danish individuals

BackgroundIn Europeans, 45 genetic risk variants for coronary artery disease (CAD) have been identified in genome-wide association studies. We constructed a genetic risk score (GRS) of these variants to estimate the effect on incidence and clinical predictability of myocardial infarction (MI) and CAD. MethodsGenotype was available from 6041 Danes. An unweighted GRS was constructed by making a summated score of the 45 known genetic CAD risk variants. Registries provided information (mean follow-up = 11.6 years) on CAD (n = 374) and MI (n = 124) events. Cox proportional hazard estimates with age as time scale was adjusted for sex, BMI, type 2 diabetes mellitus and smoking status. Analyses were also stratified either by sex or median age (below or above 45 years of age). We estimated GRS contribution to MI prediction by assessing net reclassification index (NRI) and integrated discrimination improvement (IDI) added to the European SCORE for 10-year MI risk prediction. ResultsThe GRS associated significantly with risk of incident MI (allele-dependent hazard ratio (95%CI): 1.06 (1.02–1.11), p = 0.01) but not with CAD (p = 0.39). Stratification revealed association of GRS with MI in men (1.06 (1.01–1.12), p = 0.02) and in individuals above the median of 45.11 years of age (1.06 (1.00–1.12), p = 0.03). There was no interaction between GRS and gender (p = 0.90) or age (p = 0.83). The GRS improved neither NRI nor IDI. ConclusionThe GRS of 45 GWAS identified risk variants increase the risk of MI in a Danish cohort. The GRS did not improve NRI or IDI beyond the performance of conventional European SCORE risk factors.

Does oral calcium intake or body habitus relate to the degree of valvular calcification and adverse events in patients with severe aortic stenosis?

The safety of calcium supplements has drawn much controversy, especially since its use is becoming more prevalent. A recent meta-analysis shows that there is an increased risk of incident myocardial infarction in patients taking calcium [ [1] Bolland M. Avenell A. Baron J. et al. Effects of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010; 341: c3691 Crossref PubMed Scopus (850) Google Scholar ]. While calcium use appears to contribute to the risk of cardiovascular events, it does not seem to have an effect on aortic valve calcification (AVC). A study on patients taking calcium supplementation demonstrates that these subjects do not experience an accelerated rate of progression in AVC [ [2] Bhakta M. Bruce C. Messika-Zeitoun D. et al. Oral calcium supplements do not affect the progression of aortic valve calcification or coronary artery calcification. J. Am.Board Fam. Med. 2009; 22: 610-616 Crossref PubMed Scopus (24) Google Scholar ]. The relationship between body mass index (BMI) and cardiovascular events in aortic stenosis (AS) has also been well-established. It is found that in asymptomatic patients with AS, being overweight or obese does not influence AS progression or rate of AS-related or ischemic cardiovascular events but is associated with increased mortality [ [3] Rogge B. Cramariuc D. Lønnebakken M. et al. Effect of overweight and obesity on cardiovascular events in asymptomatic aortic stenosis: a SEAS substudy (Simvastatin Ezetimibe in Aortic Stenosis). J. Am. Coll. Cardiol. 2013; 62: 1683-1690 Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar ]. Overall, there are limited studies examining the relationships between calcium use, BMI and cardiovascular events in patients with severe AS. Corrigendum to “Does oral calcium intake or body habitus relate to the degree of valvular calcification and adverse events in patients with severe aortic stenosis?” [Int. J. Cardiol. 180 (2015) 74–75]International Journal of CardiologyVol. 199PreviewWe sincerely apologize for the amendments caused and thank you very much for your help. Full-Text PDF Corrigendum to “Does oral calcium intake or body habitus relate to the degree of valvular calcification and adverse events in patients with severe aortic stenosis?” [Int. J. Cardiol. 180C (2014) 74–75]International Journal of CardiologyVol. 191PreviewThe authors regret for the error occurred in Table 2 and the corrected version is provided below. Full-Text PDF

AB1078 Colchicine Use and Risk of Myocardial Infarction among Gout Patients - A General Population Study

BackgroundA recent randomized trial demonstrated a 77% reduced risk of myocardial infarction (MI) among adults with known coronary artery disease treated with long-term low dose colchicine.1 Whether colchicine reduces the...

Abstract P014: Clinically Significant Novel Biomarkers for Prediction of First-ever Myocardial Infarction-The Tromsø Study

Background: Identification of individuals with high risk for first-ever myocardial infarction (MI) can be improved. The objectives of the study ere to survey multiple protein biomarkers for association with the 5-year risk of incident MI and identify a clinically significant risk model that adds information to current common risk models. Methods: We employed an immunoassay platform that utilizes a sensitive, sample efficient molecular counting technology to measure 51 proteins in samples from the fourth survey (1994) in the Tromsø Study, a longitudinal study of men and women in Tromsø, Norway. A nested case control design was used with 182 first-ever MI cases (60 females/122 males) and 467 controls (277 females/190 males). Results: Of the proteins measured, 21 were predictors of MI before and after adjustment for traditional risk factors either in men, women or both. In stepwise multivariable analysis with these biomarkers and traditional risk factors, kallikrein; OR 0.58 (95% CI 0.47 - 0.71), matrix metalloproteinase 8; OR 1.41 (1.13 - 1.75), the interaction term CCL5/RANTES*women; OR 0.57 (0.44 - 0.74), the interaction term apolipoprotein B/apolipoprotein A1 ratio*men; OR 1.53 (1.27 - 1.84) and lipoprotein a; OR 1.33 (1.10 - 1.61) added significantly to the model with a net reclassification improvement of 0.10 (p=0.01), while the ROC area increased from 0.77 to 0.83, p&lt;0.001. Conclusion: Novel protein biomarker models improve identification of MI risk above and beyond traditional risk factors with more than 10% better allocation to either high or low risk group than traditional risk factors alone.

Atrial Fibrillation and the Risk of Myocardial Infarction

Myocardial infarction (MI) is an established risk factor for atrial fibrillation (AF). However, the extent to which AF is a risk factor for MI has not been investigated. To examine the risk of incident MI associated with AF. A prospective cohort of 23,928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, with follow-up through December 2009. Expert-adjudicated total MI events (fatal and nonfatal). Over 6.9 years of follow-up (median 4.5 years), 648 incident MI events occurred. In a sociodemographic-adjusted model, AF was associated with about 2-fold increased risk of MI (hazard ratio [HR], 1.96 [95% CI, 1.52-2.52]). This association remained significant (HR, 1.70 [95% CI, 1.26-2.30]) after further adjustment for total cholesterol, high-density lipoprotein cholesterol, smoking status, systolic blood pressure, blood pressure-lowering drugs, body mass index, diabetes, warfarin use, aspirin use, statin use, history of stroke and vascular disease, estimated glomerular filtration rate, albumin to creatinine ratio, and C-reactive protein level. In subgroup analysis, the risk of MI associated with AF was significantly higher in women (HR, 2.16 [95% CI, 1.41-3.31]) than in men (HR, 1.39 [95% CI, 0.91-2.10]) and in blacks (HR, 2.53 [95% CI, 1.67-3.86]) than in whites (HR, 1.26 [95% CI, 0.83-1.93]); for interactions, P = .03 and P = .02, respectively. On the other hand, there were no significant differences in the risk of MI associated with AF in older (≥75 years) vs younger (<75 years) participants (HR, 2.00 [95% CI, 1.16-3.35] and HR, 1.60 [95% CI, 1.11-2.30], respectively); for interaction, P = .44. AF is independently associated with an increased risk of incident MI, especially in women and blacks. These findings add to the growing concerns of the seriousness of AF as a public health burden: in addition to being a well-known risk factor for stroke, AF is also associated with increased risk of MI.

Changes in Traffic Exposure and the Risk of Incident Myocardial Infarction and All-Cause Mortality

Traffic-related exposures, such as air pollution and noise, have been associated with increased cardiovascular morbidity and mortality. Few studies, however, have been able to examine the effects of changes in exposure on changes in risk. Our objective was to explore the associations of changes in traffic exposure with changes in risk between 1990 and 2008 in the Nurses' Health Study. Incident myocardial infarction (MI) and all-cause mortality were prospectively identified. As a proxy for traffic exposure, we calculated residential distance to roads at all residential addresses 1986-2006 and considered addresses to be "close" or "far" based on distance and road type. To examine the effect of changes in exposure, each consecutive pair of addresses was categorized as: (1) consistently close, (2) consistently far, (3) change from close to far, and (4) change from far to close. We also examined the change in NO2 levels between address pairs. In time-varying Cox proportional hazards models adjusted for a variety of risk factors, women living at residences consistently close to traffic were at a higher risk of an incident MI (hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 1.01-1.22) and a higher risk of all-cause mortality (1.05; 1.00-1.10), compared with those consistently far. The highest risks were seen among women who moved from being far from traffic to close (incident MI: HR = 1.50 [95% CI = 1.11-2.03]; all-cause mortality: HR = 1.17 [95% CI = 1.00-1.37]). Each 1 ppb increase in NO2 compared with the previous address was associated with a HR = 1.22 for incident MI (95% CI = 0.99-1.50) and 1.03 for all-cause mortality (95% CI = 0.92-1.15). Our results suggest that changes in traffic exposure (measured as roadway proximity or change in NO2 levels) are associated with changes in risk of MI and all-cause mortality.

Serum calcium and the calcium-sensing receptor polymorphism rs17251221 in relation to coronary heart disease, type 2 diabetes, cancer and mortality: the Tromsø Study

Serum calcium measured in 27,158 subjects in 1994 and the calcium-sensing receptor polymorphism rs17251221 genotyped in 9,404 subjects were related to cardiovascular risk factors, incident myocardial infarction (MI), type 2 diabetes (T2DM), cancer and death during follow-up until 2008-2010. In a Cox regression model with adjustment for age, gender, smoking and body mass index, subjects with serum calcium 2.50-2.60mmol/L had a significantly increased risk of incident MI [n=1,802, hazards ratio (HR) 1.40, 95% confidence interval (CI) 1.18, 1.66] and T2DM (n=705, HR 1.49,95% CI 1.15, 1.94) and a significantly reduced risk of cancer (n=2,222, HR 0.73, 95% CI 0.62, 0.86) as compared to subjects with serum calcium 2.20-2.29mmol/L. For rs17251221 there was a mean difference in serum calcium of 0.05mmol/L between major and minor homozygote genotypes. No consistent, significant relation between rs17251221 and risk factors or the major hard endpoints were found. The minor homozygote genotype (high serum calcium) had a significant twofold increased risk (HR 2.32, 95% CI 1.24, 4.36) for prostate cancer, as compared to the major homozygote. This may be clinically important if confirmed in other cohorts.

Abstract 50: Cardiovascular Event Rates Among Adults with Type 2 Diabetes Mellitus at Risk of Cardiovascular Events in the Large Population-based Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes (SHIELD)

Objectives: This study ascertained the incidence and time to first non-fatal myocardial infarction (MI), stroke, heart bypass surgery, or angioplasty among adults with type 2 diabetes mellitus (T2DM) at high risk for cardiovascular disease (CVD) over 3 and 5 years using a large US population based study. Methods: A retrospective cohort study used data from the US population-based SHIELD, a 5-year prospective survey-based study of adults with and without T2DM. Respondents with T2DM were stratified into 2 cohorts: (1) established CVD cohort, with age ≥40 years, prior MI, prior stroke, atherosclerosis, or peripheral vascular disease, and (2) multiple risk factors cohort (men ≥55 years and women ≥60 years and ≥1 risk factors of hyperlipidemia, hypertension, currently smoking, without prior history of CVD). Proportion of respondents self-reporting a new MI, stroke, angioplasty, or heart bypass surgery was calculated and multivariate discrete logistic hazards models for 3 and 5 years of follow-up were developed. Results: Among 2122 T2DM respondents, 56.5% had established CVD (mean age = 65 years, 45% male); 43.5% had no established CVD but multiple risk factors (mean age = 68 years, 49% male). The established CVD cohort had a new MI, stroke, or revascularization event rate of 26.3% during a 3 year follow-up period and 31.2% during the 5 years of follow-up. For the multiple risk factors cohort, 18.8% within 3 years and 26.0% within 5 years had an incident MI, stroke, or revascularization. After adjusting for gender, age, obesity, duration of diabetes, and comorbidities, the risk of incident MI was 2.1 times higher (95% CI: 1.6-2.8) within 3 years and 1.9 times higher (1.5-2.4) within 5 years of follow-up among the established CVD cohort than multiple risk factors cohort (p&lt;0.001). Risk of incident stroke was 2.2 (1.4-3.5) and 1.8 (1.2-2.7) times higher within 3 and 5 years, respectively, after adjustment among the established CVD cohort than multiple risk factors cohort (p &lt;0.01). Risk of incident heart bypass surgery was 2.6 (1.7-4.2) and 2.5 (1.7-3.8) times higher, and risk of incident angioplasty was 3.9 (2.7-5.9) and 3.2 (2.3-4.5) times higher within 3 and 5 years, respectively, among the established CVD cohort than multiple risk factors cohort (p &lt;0.001). Conclusions: T2DM individuals at risk for CVD events had significant incidence of MI, stroke, and revascularization in this large US population-based study. T2DM adults with established CVD are at higher risk of CVD events than those with no CVD but have multiple risk factors.

Genetic variants from lipid-related pathways and risk for incident myocardial infarction.

BackgroundCirculating lipids levels, as well as several familial lipid metabolism disorders, are strongly associated with initiation and progression of atherosclerosis and incidence of myocardial infarction (MI).ObjectivesWe hypothesized that genetic variants associated with circulating lipid levels would also be associated with MI incidence, and have tested this in three independent samples.Setting and SubjectsUsing age- and sex-adjusted additive genetic models, we analyzed 554 single nucleotide polymorphisms (SNPs) in 41 candidate gene regions proposed to be involved in lipid-related pathways potentially predisposing to incidence of MI in 2,602 participants of the Swedish Twin Register (STR; 57% women). All associations with nominal P<0.01 were further investigated in the Uppsala Longitudinal Study of Adult Men (ULSAM; N = 1,142).ResultsIn the present study, we report associations of lipid-related SNPs with incident MI in two community-based longitudinal studies with in silico replication in a meta-analysis of genome-wide association studies. Overall, there were 9 SNPs in STR with nominal P-value <0.01 that were successfully genotyped in ULSAM. rs4149313 located in ABCA1 was associated with MI incidence in both longitudinal study samples with nominal significance (hazard ratio, 1.36 and 1.40; P-value, 0.004 and 0.015 in STR and ULSAM, respectively). In silico replication supported the association of rs4149313 with coronary artery disease in an independent meta-analysis including 173,975 individuals of European descent from the CARDIoGRAMplusC4D consortium (odds ratio, 1.03; P-value, 0.048).Conclusionsrs4149313 is one of the few amino acid changing variants in ABCA1 known to associate with reduced cholesterol efflux. Our results are suggestive of a weak association between this variant and the development of atherosclerosis and MI.

Subclinical Hypothyroidism and Risk for Incident Myocardial Infarction Among Postmenopausal Women

Subclinical hypothyroidism (SCH) has been associated with an increased risk for cardiovascular disease. However, few studies have specifically examined the association between SCH and myocardial infarction (MI), and the relationship is poorly understood. The purpose of this study was to evaluate incident MI risk in relation to SCH and severities of SCH among postmenopausal women. We used a population-based nested case-cohort design within the Women's Health Initiative observational study to examine the association between SCH and incident first-time MI risk among postmenopausal women in the United States. SCH was assessed using blood specimens collected at baseline. Participants presenting with normal free T4 levels and with thyrotropin levels of greater than 4.68-6.99 mU/L or 7.00 mU/L or greater were defined as having mild SCH or moderate/severe SCH, respectively. MI cases were centrally adjudicated by trained Women's Health Initiative staff. The primary analysis included 736 incident MI cases and 2927 randomly selected subcohort members. Multivariable adjusted Cox-proportional hazard models were used to assess MI risk in relation to SCH. Compared with euthyroid participants, the multivariable adjusted hazard ratio (HR) for participants with any SCH was 1.05 [95% confidence interval (CI) 0.77-1.44]. HRs for participants with mild SCH, moderate/severe SCH, and moderate/severe SCH and the presence of antithyroid peroxidase antibodies (TPOAb) were 0.99 (95% CI 0.67-1.46), 1.19 (95% CI 0.72-1.96), and 0.90 (95% CI 0.47-1.74), respectively. We did not find evidence to suggest that SCH is associated with increased MI risk among a population of predominantly older postmenopausal women with no prior history of MI.