Stockholm Heart Epidemiology Program Research Articles

Bereavement in the year before a first myocardial infarction: Impact on prognosis.

Death of the spouse in middle and old age is associated with an increased risk of cardiovascular and total mortality, particularly during the months after the loss. Knowledge regarding the effect of bereavement on prognosis in acute myocardial infarction (AMI) is limited. We analysed whether bereavement the year before the AMI is associated with prognosis. We studied first AMI patients who participated in the Stockholm Heart Epidemiology Program (N = 1732). During or shortly after the hospitalization, patients or their family members completed a questionnaire regarding bereavement, sociodemographic, clinical and lifestyle factors; five months after their first infarction, surviving patients attended a clinical examination. Participants were followed for cardiovascular events and mortality for a median of 14 years. Overall bereavement, that is, death of a close friend or family member (including spouse/partner), the year before the first AMI was not associated with the combined outcome of non-fatal recurrent AMI and death due to ischaemic heart diseases. However, exposure to the loss of the spouse/partner was associated with an increased risk of the outcome (adjusted hazard ratio and (95% confidence interval): 1.55 (1.06-2.27)). We found no evidence that psychiatric disorders or blood lipids, glucose, coagulation and inflammatory markers mediated this association. Loss of spouse/partner the year before the first AMI was associated with an increased risk of the combination of non-fatal recurrent AMI and death due to ischaemic heart disease. If confirmed by others, the findings may be informative for tertiary prevention of AMI.

PAI-1 level and the PAI-1 4G/5G polymorphism in relation to risk of non-fatal myocardial infarction: results from the Stockholm Heart Epidemiology Program (SHEEP).

This study examines the relationship between plasma Plasminogen Activator Inhibitor-1 (PAI-1) activity and the PAI-1 4G/5G polymorphism, and their association with the risk of myocardial infarction (MI). Furthermore, this study explores whether a high level of PAI-1 or whether the PAI-1 4G/5G polymorphism synergistically interacts with any established environmental risk factor for MI. This case-referent study of subjects aged 45-70 and living in Stockholm includes 851 men and 361 women with first-time MI and 1051 men and 505 women who were randomly chosen as referents from a population register. The adjusted odds ratio (OR) of MI was 1.9 (95% confidence interval [CI] 1.4-2.8) for men with a plasma PAI-1 activity level greater than the 90 th percentile value of referents. The corresponding OR for women was 1.5 (95% CI 0.9-2.5). A strong indication of synergistic interaction was found in men for the co-exposure to high plasma PAI-1 activity and current smoking, an adjusted synergy index score of 3.9 (95% CI 1.2-13.2). In women, the 4G allele was associated slightly with an increased risk of MI, OR 1.4 (95% CI 1.0-1.9). This association was not found in men. There were no clear indications of synergistic interaction effects involving the PAI-1 4G/5G polymorphism and the environmental exposures considered (cigarette smoking, physical inactivity, overweight, diabetes mellitus, hypercholesterolaemia, hypertension, high C-reactive protein and hypertriglyceridaemia).

Job strain predicts recurrent events after a first acute myocardial infarction: The Stockholm Heart Epidemiology Program

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Agreement between Myocardial Infarction Patients and Their Spouses on Reporting of Data on 82 Cardiovascular Risk Exposures.

BackgroundThe validity of exposure data collected from proxy respondents of myocardial infarction patients has scarcely been studied. We assessed the level of disagreement between myocardial infarction patients and their spouses with respect to the reporting of the patient´s cardiovascular risk exposures.MethodsWithin the frame of the Stockholm Heart Epidemiology Program (SHEEP), a case-control study of risk factors of myocardial infarction performed in Stockholm county 1992–1994, a subset of 327 first time myocardial infarction cases aged 45–70 who survived >28 days after the event and who co-habited with a spouse or common-law spouse (proxy) were identified between 1993-04-05 and 1993-12-31. Among these, 243 cases participated along with their respective proxy in the present study. Control individuals, matched to cases by age, sex and residential area were also included (n = 243). Data were collected using questionnaires. Using conditional logistic regression we calculated for each of 82 exposures the odds ratio based on information collected from 1) myocardial infarction cases and controls [odds ratio A] and 2) proxies and the same set of controls [odds ratio B]. Disagreement was measured by calculating the ratio between odds ratio B and odds ratio A with 95% confidence intervals (CI) calculated using resampling bootstrap.ResultsFor the vast majority of the exposures considered including diet, smoking, education, work-related stress, and family history of CVD, there was no statistically significant disagreement between myocardial infarction patients and proxies (n = 243 pairs). However, leisure time physical inactivity (proxy bias = 1.59, 95% CI 1.05-3.57) was overestimated by spouses compared to myocardial infarction patients. A few other exposures including some sleep-related problems and work-related issues also showed disagreement.ConclusionsMyocardial infarction patients and their spouses similarly reported data on a wide range of exposures including the majority of the traditional cardiovascular risk factors, leisure time physical inactivity being an exception.

Circulating levels of interleukin 6 soluble receptor and its natural antagonist, sgp130, and the risk of myocardial infarction

ObjectiveTo investigate the association between circulating levels of the soluble interleukin 6 receptor (sIL6R) and the soluble gp130 (sgp130) with myocardial infarction (MI) and to explore the potential interaction between sIL6R and sgp130 in this association. MethodsStudy population is the Stockholm Heart Epidemiology Program (SHEEP), a population-based case–control study. SIL6R (ng/mL) and sgp130 (ng/mL) levels were measured in serum samples from 682 and 664 MI cases and 1103 and 1062 controls, respectively. Odds ratios (with 95% CIs) for MI were calculated using unconditional logistic regression. We adjusted for age, sex, hospital catchment area (crude) and for hypertension, diabetes, hypercholesterolemia, body mass index and smoking (adjusted model). Synergy index (S) and attributable proportion (AP) were estimated as measures of biological interaction. ResultsElevated concentrations of sIL6R (>75th percentile value) were associated with an increased occurrence of MI (compared to ≤75th percentile), with an adjusted OR of 1.4 (95% CI, 1.1–1.8). Very high (>90th percentile value) levels of sgp130 were associated with a reduced occurrence of MI [OR 0.7 (95% CI, 0.5–0.9)] (adjusted). There was an indication of a possible interaction between high sIL6R and low sgp130 (adjusted S score 1.7, 95% CI = 0.5–6.1; AP 0.19, 95% CI = −0.2–0.5), suggesting that low sgp130 levels may synergize with high sIL6R levels to increase risk of MI. ConclusionssIL6R and sgp130 had opposing associations with MI. Indeed, circulating sgp130 levels may modify the association of elevated sIL6R levels with MI.

Duffy antigen receptor genetic variant and the association with Interleukin 8 levels

The aim of this study is to identify loci associated with circulating levels of Interleukin 8 (IL8). We investigated the associations of 121,445 single nucleotide polymorphisms (SNPs) from the Illumina 200K CardioMetabochip with IL8 levels in 1077 controls from the Stockholm Heart Epidemiology Program (SHEEP) study, using linear regression under an additive model of inheritance.Five SNPs (rs12075A/G, rs13179413C/T, rs6907989T/A, rs9352745A/C, rs1779553T/C) reached the pre-defined threshold of genome-wide significance (p<1.0×10−5) and were tested for in silico replication in three independent populations, derived from the PIVUS, MDC-CC and SCARF studies. IL8 was measured in serum (SHEEP, PIVUS) and plasma (MDC-CC, SCARF). The strongest association was found with the SNP rs12075 A/G, Asp42Gly (p=1.6×10−6), mapping to the Duffy antigen receptor for chemokines (DARC) gene on chromosome 1. The minor allele G was associated with 15.6% and 10.4% reduction in serum IL8 per copy of the allele in SHEEP and PIVUS studies respectively. No association was observed between rs12075 and plasma IL8.Conclusion: rs12075 was associated with serum levels but not with plasma levels of IL8. It is likely that serum IL8 represents the combination of levels of circulating plasma IL8 and additional chemokine liberated from the erythrocyte DARC reservoir due to clotting. These findings highlight the importance of understanding IL8 as a biomarker in cardiometabolic diseases.

Does menopausal hormone therapy reduce myocardial infarction risk if initiated early after menopause? A population-based case-control study.

This study aims to assess whether the timing of menopausal hormone therapy initiation in relation to onset of menopause and hormone therapy duration is associated with myocardial infarction risk. This study was based on the Stockholm Heart Epidemiology Program, a population-based case-control study including 347 postmenopausal women who had experienced a nonfatal myocardial infarction and 499 female control individuals matched for age and residential area. Odds ratios (with 95% CIs) for myocardial infarction were calculated using logistic regression. Early initiation of hormone therapy (within 10 y of onset of menopause or before age 60 y), compared with never use, was associated with an odds ratio of 0.87 (95% CI, 0.58-1.30) after adjustments for lifestyle factors, body mass index, and socioeconomic status. For late initiation of hormone therapy, the corresponding odds ratio was 0.97 (95% CI, 0.53-1.76). For hormone therapy duration of 5 years or more, compared with never use, the adjusted odds ratio was 0.64 (95% CI, 0.35-1.18). For hormone therapy duration of less than 5 years, the odds ratio was 0.97 (95% CI, 0.63-1.48). Neither the timing of hormone therapy initiation nor the duration of therapy is significantly associated with myocardial infarction risk.

Case fatality of myocardial infarction among shift workers.

Shift work has been associated with an excess risk of cardiovascular disease (CVD) and more specifically myocardial infarction (MI). The majority of the studies that found a positive association between shift work and CVD have been based on incidence data. The results from studies on cardiovascular-related mortality among shift workers have shown little or no elevated mortality associated with shift work. None of the previous studies have analysed short-term mortality (case fatality) after MI. Therefore, we investigated whether shift work is associated with increased case fatality after MI compared with day workers. Data on incident cases with first MI were obtained from case-control study conducted in two geographical sites in Sweden (Stockholm Heart Epidemiology Program and Västernorrland Heart Epidemiology Program), including 1,542 cases (1,147 men and 395 women) of MI with complete working time information and 65 years or younger. Case fatality was defined as death within 28 days of onset of MI. Risk estimates were calculated using logistic regression. The crude odds ratios for case fatality among male shift workers were 1.63 [95 % confidence interval (CI) 1.12, 2.38] and 0.56 (95 % CI 0.26, 1.18) for female shift workers compared with day workers. Adjustments for established cardiovascular risk factors such as diabetes type II and socio-economic status did not alter the results. Shift work was associated with increased risk of case fatality among male shift workers after the first MI.

Sleep impairment and prognosis of acute myocardial infarction: a prospective cohort study.

Impaired sleep is an established risk factor for the development of cardiovascular disease, whereas less is known about how impaired sleep affects cardiovascular prognosis. The aim of this study is to determine how different aspects of impaired sleep affect the risk of case fatality and subsequent cardiovascular events following first-time acute myocardial infarction (AMI). Prospective cohort study. The Stockholm Heart Epidemiology Program, Sweden. There were 2,246 first-time AMI cases. Sleep impairment was assessed by the Karolinska Sleep Questionnaire, which covers various indices of impaired sleep: disturbed sleep, impaired awakening, daytime sleepiness, and nightmares. Case fatality, defined as death within 28 days of initial AMI, and new cardiovascular events within up to 10 y of follow-up were identified through national registries. In women, disturbed sleep showed a consistently higher risk of long-term cardiovascular events: AMI (hazard ratio [HR] = 1.69; 95% confidence interval [CI] 0.95-3.00), stroke (HR = 2.61; 95% CI: 1.19-5.76), and heart failure (HR = 2.43; 95% CI: 1.18-4.97), whereas no clear effect of impaired sleep on case fatality was found in women. In men, a strong effect on case fatality (odds ratio = 3.27; 95% CI: 1.76-6.06) was observed in regard to impaired awakening; however, no consistent effect of impaired sleep was seen on long-term cardiovascular prognosis. Results suggest sex-specific effects of impaired sleep that differ by short- and long-term prognosis. Sleep complaints are frequent, easily recognizable, and potentially manageable. Evaluation of sleep complaints may, even if they represent prognostic markers rather than risk factors, provide additional information in clinical risk assessment that could benefit secondary cardiovascular prevention.

Association of interleukin 8 with myocardial infarction: Results from the Stockholm Heart Epidemiology Program

BackgroundInterleukin 8 (IL8) has been contradictorily associated with the risk of myocardial infarction (MI). AimTo investigate the association of IL8 serum levels with the risk of MI and the association of the IL8 (IL8) and IL8 receptors (CXCR1 and CXCR2) genetic variants with IL8 levels and MI risk in a large case control study, the Stockholm Heart Epidemiology Program. Methods and resultsIL8 levels (pg/mL) were divided into quartiles and the MI risk was calculated by logistic regression and expressed as odds ratio (OR) and 95% CI. Two IL8 SNPs (rs4073A/T, rs2227306C/T) and three SNPs tagging CXCR1 and CXCR2 (rs4674258C/T, rs1008563C/T, rs6723449T/C) were analyzed for association with IL8 levels and with MI risk.Multivariate adjusted ORs for MI risk by IL8 levels in the highest quartiles indicated reduced point estimates in both women (OR 0.37; 95% CI 0.2–0.8) and men when compared to the lowest quartile. In female cases, IL8 levels decreased progressively in the six months after MI (p=0.03). IL8, CXCR1 and CXCR2 genetic variants were not associated with IL8 levels. In men, the T allele at the IL8 SNP rs4073 was associated with a slight increase in the MI risk under an additive and a recessive model of inheritance. ConclusionsIL8 serum levels were associated with a reduced occurrence of MI among women, whereas IL8 was associated with a slightly increased risk among men, possibly through different mechanisms. These data suggest that the biological effects of IL8 on MI risk may vary over time and warrant further cohort studies with repetitive IL8 measurements.

The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism

ObjectiveAn elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic...

Interaction between air pollution exposure and genes in relation to levels of inflammatory markers and risk of myocardial infarction

ObjectivesAir pollution exposure induces cardiovascular effects, possibly via systemic inflammation and coagulation misbalance. Genetic variation may determine individual susceptibility. Our aim was to investigate effect modification by inflammation (Interleukin6 (IL6),...

Interleukin 8 serum levels and the risk of myocardial infarction. Results from the Stockholm Heart Epidemiology program

Since its discovery during the late 80s, a large body of evidence suggests a key role of interleukin 8 (IL8) in the natural history of atherosclerosis from the early stages of vascular inflammation to the remodeling after myocardial infarction (MI). The aim of the present study was to evaluate the association of IL8 serum levels with the risk of MI in men and women from the Stockholm Heart Epidemiology Program (SHEEP), a case-control population with 2774 subjects (cases n=1213 and controls n=1561). Cases were identified as patients having been diagnosed with a non-fatal MI and controls were sex and age-matched subjects. Blood samplings were performed at least three months after the MI. IL8 (pg/ml) was measured in serum samples from 1133 controls and 714 cases using the Meso Scale Discovery's Multi-Array. IL8 serum levels were divided in quartiles according to IL8 distribution in controls (Q1≤ 8.3, Q2>8.3≤13.6, Q3>13.6≤20.9, Q4>20.9) In women, serum IL8 levels were higher in controls 14.2 (8.7-22.1) than in cases 11.6 (6.6-18.0) p= 0.0002 and strongly related to a protective effect of first time MI. Women with IL8 serum levels in the highest quartile (Q4) had an unadjusted OR of 0.44 (95% CI, 0.3-0.7), as compared to women exposed to low IL8 (Q1). Adjustments by insulin, BMI and CRP (OR [95% CI] = 0.41 [0.2-0.7]) and additional adjustment for the traditional cardiovascular risk factors (OR [95% CI] = 0.35 [0.2-0.6]) and by drug therapy (OR [95% CI] = 0.37 [0.2-0.8]) did not significantly change the risk estimates. In men serum levels of IL8 were higher in controls than in cases and associated with a reduced, however non-significant, MI risk. We report the largest investigation performed so far on the association between IL8 serum levels and the risk of MI. Our data demonstrates that in women high IL8 serum levels are associated with a reduced risk of MI. This may reflect a shift in the IL-8 properties during the different stages of the atherosclerotic process from a pro-inflammatory to an anti-inflammatory, pro-angiogenetic cytokine.

Chromosome 1p13 genetic variants antagonize the risk of myocardial infarction associated with high ApoB serum levels

BackgroundGenetic variation at 1p13 modulates serum lipid levels and the risk of coronary heart disease through the regulation of serum lipid levels. Here we investigate if the interaction between genetic variants at 1p13 and serum lipid levels affects the risk of non-fatal myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP), a large population based case control study.MethodsIn the present study only non fatal MI cases (n = 1213, men/women: 852/361) and controls (n = 1516, men/women =1054/507) matched by age, sex and residential area, were included. Three SNPs 12740374 G/T, rs599839A/G and rs646776T/C mapping at 1p13 were analysed for association with serum lipid levels and the risk of MI by a weighted least square regression and logistic regression analyses, respectively. To analyse the effect of the interaction between genetic variants and serum lipid levels on the risk of MI, we applied the biological model of interaction that estimates the difference in risk, expressed as OR (95%CI), observed in the presence and in the absence of both exposures. One derived measure is the Synergy index (S) and 95%CI, where S > 1 indicates synergy and S < 1 antagonism between the two interaction terms.ResultsRs12740374G/T and rs646776T/C were in strong linkage disequilibrium (LD) (r2 = 0.99), therefore only rs599839A/G and rs646776 were included in the analysis. Consistently with published data, presence of the rare genotypes was associated with reduced total-, LDL-cholesterol and ApoB serum levels (all p < 0.05) as compared to the reference genotype, but was not associated with the risk of MI.However, the increased risk of MI observed in individual exposed to high (≥75th percentile) serum lipid levels was offset in subjects carrying the rare alleles G and C. In particular, the risk of MI associated with high ApoB serum levels OR (95%CI) 2.27 (1.86-2.77) was reduced to 1.76 (1.33-2.34) in the presence of the G allele at rs599839 with an S of 0.47 (0.20-0.90).ConclusionsThese results indicate that an antagonism between ApoB serum levels and genetic variants at 1p13 contributes to reduce the risk of non-fatal MI in the presence of high ApoB serum levels.

Job insecurity and prognosis after myocardial infarction: The SHEEP Study

BackgroundThe prognostic role of job insecurity in coronary heart disease is unknown. We aimed to analyze whether job insecurity predicts mortality and recurrent events after a first acute myocardial infarction (AMI). MethodsWe studied non-fatal AMI cases involved in the Stockholm Heart Epidemiology Program who were in paid employment and younger than 65years (n=676). Shortly after their AMI, patients completed a questionnaire about job insecurity, demographic, work-related, clinical and lifestyle factors and participated in a clinical examination three months after discharge from the hospital. They were followed for 8.5years for mortality and cardiovascular events. ResultsAfter adjusting for previous morbidity, demographic and work-related factors, job insecurity was associated with an increased risk of the combined endpoint of cardiac death and non-fatal AMI, of total mortality and of heart failure; the hazard ratios (HR) and the 95% confidence intervals (CI) were 1.50 (1.02-2.22), 1.69 (1.04-2.75) and 1.62 (1.07-2.44), respectively. Similar associations, but with less statistical power were observed between job insecurity and cardiac death (HR (95% CI): 1.57 (0.80-3.09)) and stroke (HR (95% CI): 1.46 (0.71-3.02)), respectively. Adjustment for potential mediators, i.e. sleep problems, health behaviour, hypertension, blood lipids, glucose, inflammatory and coagulation factors did not alter considerably the relationship between job insecurity and the combination of cardiac mortality and non-fatal AMI. ConclusionsOur results suggest that job insecurity is an adverse prognostic factor in patients with a first AMI. Future studies are needed to confirm this finding and to determine the mechanisms underlying the observed relationship.

Sexual Activity and Cardiovascular Disease

Sexual activity is an important component of patient and partner quality of life for men and women with cardiovascular disease (CVD), including many elderly patients.1 Decreased sexual activity and function are common in patients with CVD and are often interrelated to anxiety and depression.2,3 The intent of this American Heart Association Scientific Statement is to synthesize and summarize data relevant to sexual activity and heart disease in order to provide recommendations and foster physician and other healthcare professional communication with patients about sexual activity. Recommendations in this document are based on published studies, the Princeton Consensus Panel,4,5 the 36th Bethesda Conference,6–10 European Society of Cardiology recommendations on physical activity and sports participation for patients with CVD,11–13 practice guidelines from the American College of Cardiology/American Heart Association14–16 and other organizations,17 and the multidisciplinary expertise of the writing group. The classification of recommendations in this document are based on established ACCF/AHA criteria (Table). View this table: Table. Applying Classification of Recommendation and Level of Evidence Numerous studies have examined the cardiovascular and neuroendocrine response to sexual arousal and intercourse, with most assessing male physiological responses during heterosexual vaginal intercourse.18–24 During foreplay, systolic and diastolic systemic arterial blood pressure and heart rate increase mildly, with more modest increases occurring transiently during sexual arousal. The greatest increases occur during the 10 to 15 seconds of orgasm, with a rapid return to baseline systemic blood pressure and heart rate thereafter. Men and women have similar neuroendocrine, blood pressure, and heart rate responses to sexual activity.24,25 Studies conducted primarily in young married men showed that sexual activity with a person's usual partner is comparable to mild to moderate physical activity in the range of 3 to …

Impaired fibrinolytic capacity and increased fibrin formation associate with myocardial infarction

We assessed whether abnormality of haemostasis measured by a newly developed global method is associated with risk of a first myocardial infarction (MI). The global markers coagulation activation profile (Cp), fibrinolysis activation profile (Fp) and sum of fibrin optical density over time (Fibrin OD-sum) were determined in plasma from 800 MI cases and 1,123 controls included in the Stockholm Heart Epidemiology Program. Clot lysis time (CLT) was also determined based on raw data of fibrin OD from the global assay. Odds ratios (OR) of MI with 95% confidence intervals (CI) were calculated using logistic regression. A Fp value <10th percentile value in controls was significantly associated with increased MI risk; OR after multivariate adjustments for conventional cardiovascular risk factors 1.66 (95% CI 1.22-2.27). For an abnormally long CLT (>90th percentile value in controls) the adjusted OR of MI was 2.62 (95% CI 1.87-3.66) and for a high Fibrin OD-sum value (>90th percentile in controls) it was 1.86 (95% CI 1.37-2.53). A high Cp value was not significantly associated with MI. In conclusion, we found that abnormal haemostasis in platelet-poor plasma, reflected either as an attenuated fibrinolytic capacity or the resulting increase of fibrin formation, was associated with increased MI risk.

Apolipoprotein C-I genotype and serum levels of triglycerides, C-reactive protein and coronary heart disease

Apolipoprotein C-I (apoCI) is implicated in lipid metabolism and inflammatory response, both important risk factors for human heart disease. However, most findings come from in vitro or animal studies, whereas data on human apoCI are sparse. To elucidate the role of apoCI in human disease, we analyzed a functional polymorphism in the promoter region of the apoCI gene in relation to blood lipids, C-reactive protein (CRP), coronary artery disease (CAD), and myocardial infarction (MI). Rs11568822 is a 4–base pair insertion/deletion (Ins/Del) polymorphism, and the Ins allele leads to a higher transcription in vitro compared with the Del allele. This polymorphism was analyzed in the Intergene study, a case-control study for CAD (N = 1236), and the Stockholm Heart Epidemiology Program, a case-control study for MI (N = 2774). Subjects homozygous for the Ins genotype had significantly higher serum levels of triglycerides ( P = .01 and P = .006) and lower serum levels of CRP ( P = .02 and P < .0001) compared with all other subjects in both studies. Similar results were obtained when analyzing only the controls of both studies ( P = .002 and P = .0002, triglycerides; P = .002 and P < .0001, CRP). However, apoCI was not associated with CAD or MI. In conclusion, our data show that apoCI genotype is associated with serum levels of triglycerides and CRP, confirming the role of apoCI in lipid metabolism and suggesting that it also influences inflammation.

The Interaction between Coagulation Factor 2 Receptor and Interleukin 6 Haplotypes Increases the Risk of Myocardial Infarction in Men

The aim of the study was to investigate if the interaction between the coagulation factor 2 receptor (F2R) and the interleukin 6 (IL6) haplotypes modulates the risk of myocardial infarction (MI) in the Stockholm Heart Epidemiology Program (SHEEP). Seven SNPs at the F2R locus and three SNPs at the IL6 locus were genotyped. Haplotypes and haplotype pairs (IL6*F2R) were generated. A logistic regression analysis was performed to analyze the association of the haplotypes and haplotype pairs with the MI risk. Presence of an interaction between the two haplotypes in each haplotype pair was calculated using two different methods: the statistical, on a multiplicative scale, which includes the cross product of the two factors into the logistic regression model; the biological, on an additive scale, which evaluates the relative risk associated with the joint presence of both factors. The ratio between the observed and the predicted effect of the joint exposure, the synergy index (S), indicates the presence of a synergy (S>1) or of an antagonism (S<1). None of the haplotypes within the two loci was associated with the risk of MI. Out of 22 different haplotype pairs, the haplotype pair 17 GGG*ADGTCCT was associated with an increased risk of MI with an OR (95%CI) of 1.58 (1.05–2.41) (p = 0.02) in the crude and an OR of 1.72 (1.11–2.67) (p = 0.01) in the adjusted analysis. We observed the presence of an interaction on a multiplicative scale with an OR (95%CI) of 2.24 (1.27–3.95) (p = 0.005) and a slight interactive effect between the two haplotypes on an additive scale with an OR (95%CI) of 1.56 (1.02–2.37) (p = 0.03) and S of 1.66 (0.89–31). In conclusion, our results support the hypothesis that the interaction between these two functionally related genes may influence the risk of MI and suggest new mechanisms involved in the genetic susceptibility to MI.

Job strain predicts recurrent events after a first acute myocardial infarction: the Stockholm Heart Epidemiology Program

Studies investigating the prognostic role of job stress in coronary heart disease are sparse and have inconclusive findings. We aimed (i) to investigate whether job strain predicts recurrent events after acute myocardial infarction (AMI) and if so (ii) to determine behavioural and biological factors that contribute to the explanation of this association. Prospective study. Ten emergency hospitals in the larger Stockholm area, Sweden. Non-fatal AMI cases from the Stockholm Heart Epidemiology Program case-control study who were employed and younger than 65 years at the time of their hospitalization (n = 676). During the 8.5 year follow-up, 155 patients experienced cardiac death or non-fatal AMI; totally 96 patients died, 52 of cardiac causes. After adjustment for potential confounders, patients with high job strain had an increased risk for the combination of cardiac death and non-fatal AMI relative to those with low job strain, the hazard ratio (HR) and the 95% confidence interval (CI) being 1.73 (1.06-2.83). Results were similar for cardiac [HR (95% CI): 2.81 (1.16-6.82)] and total mortality [HR (95% CI): 1.65 (0.91-2.98)]. We found no evidence for mediation from lifestyle, sleep, lipids, glucose, inflammatory and coagulation markers on the association between job strain and the combination of cardiac death and non-fatal AMI. Job strain was associated with poor long-term prognosis after a first myocardial infarction. Interventions focusing on reducing stressors at the workplace or on improving coping with work stress in cardiac patients might improve their survival post-AMI.