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Background: Myocardial infarction is likely to be experienced as a life-threatening and potentially traumatic event. Approximately one-third of patients with myocardial infarction experience clinically significant symptoms of anxiety/depression. However, it is unclear how many of these patients experience these symptoms because of post-traumatic stress disorder (PTSD). We conducted a clinical screening of individuals with a confirmed myocardial infarction diagnosis. Our goal was to examine the prevalence of PTSD in myocardial infarction patients and study how PTSD symptoms were associated with exposure to potentially traumatic events., Method: This is epidemiological research with a cross-sectional design following up participants from the Tromsø Study with a confirmed diagnosis of myocardial infarction. We sent invitations to participants in the Tromsø Study with clinically significant self-reported anxiety or depression symptoms following myocardial infarction. A cross-sectional sample of N = 79 participants (61 men and 18 women) was collected. During an interview, participants completed the Stressful Life Events Screening Questionnaire and the PTSD checklist PCL-5., Results: We found nine participants (11.6%) with probable PTSD. This was significantly higher than the postulated population prevalence in Norway (p < 0.015). We found no direct association between myocardial infarction as illness trauma and symptom levels (p = 0.123). However, we found a significant linear trend (p = 0.002), indicating that symptom severity increased proportionately as the number of post-traumatic events increased., Conclusion: PTSD prevalence in myocardial infarction patients was related to lifetime exposure to traumatic events, not the myocardial infarction event alone. More research is required to examine the interaction between myocardial infarction and PTSD. Clinicians should be aware that anxiety or depression symptoms after MI could be secondary symptoms of PTSD., (© 2023. The Author(s).)

Background The atherosclerotic effect of an adverse lipid profile is assumed to accumulate throughout life, leading to increased risk of myocardial infarction (MI). Still, little is known about age at onset and duration of unfavorable lipid levels before MI. Methods and Results Longitudinal data on serum lipid levels for 26 130 individuals (50.5% women, aged 20-89 years) were obtained from 7 population-based health surveys in Tromsø, Norway. Diagnoses of MI were obtained from national registers. A linear mixed model was applied to compare age- and sex-specific mean values of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride concentration by MI status (MI versus non-MI). Already from young adulthood, 20 to 35 years before the incident MI, individuals with a subsequent incident MI had on average more adverse lipid levels than individuals of the same age and sex without MI. Analogous to a dose-response relationship, there was a clear trend toward more severe adverse lipid levels the lower the age at incident MI ( P <0.001, test for trend through ordered categories <55, 55-74, ≥75 years). This trend was particularly pronounced for high-density lipoprotein cholesterol in percentage of total cholesterol (both sexes) and for the relative relationship between triglyceride, high-density lipoprotein cholesterol, and total cholesterol level (women). The difference in mean lipid level by MI status was just as large in women as in men, but the age pattern differed ( P ≤0.05, tests of 3-way interaction). Conclusions Compared with general population mean levels, adverse lipid levels were seen 20 to 35 years before the incident MI in both men and women.

Objective: Antidepressants are thought to affect the risk of cardiovascular disease, although the nature of the association is unclear. Men and women have unique cardiovascular risk factors, and sex differences in depression as well as the efficacy of antidepressants are important to consider. We examined whether antidepressant use was associated with risk of having a myocardial infarction (MI) and whether this association was sex-specific., Methods: Data from The Trøndelag Health Study were used, gathered from a population in Norway ( N = 31,765), collected from 1995 to 2008. These data were combined with the Norwegian Cause of Death Registry and the Norwegian Prescription Database. We performed logistic regression models to examine the association of antidepressant use on risk of having a fatal or nonfatal MI, adjusting for depression, anxiety, diabetes, systolic blood pressure, cholesterol, waist-hip ratio, smoking, age, and sex. Results are presented as odds ratios (ORs) and 95% confidence intervals in parentheses., Results: The results indicated that antidepressant use was associated with a reduced risk of having MI at a later date (OR = 0.49 [0.38-0.64]). Although this association was somewhat stronger for women (OR = 0.46 [0.31-0.68]) compared with men (OR = 0.53 [0.37-0.75]), analysis did not identify a sex-specific association of antidepressant use on MI. Follow-up analyses on different subtypes of antidepressants showed that both selective serotonin reuptake inhibitor and tricyclic antidepressant were associated with a reduced risk of MI., Conclusions: In this population study, the use of antidepressants was associated with a reduced risk of MI. This association was stronger for women, although we detected no interaction between sex and antidepressant use in terms of reduced risk of MI. Although limitations apply regarding causality, especially concerning a dose-response relationship, the results suggest that antidepressant use might reduce the risk of MI among both men and women., (Copyright © 2022 by the American Psychosomatic Society.)

Background: Myocardial infarction (MI) is associated with an increased risk of venous thromboembolism (VTE). Obesity is a recognized risk factor for both MI and VTE. Whether obesity further increases the risk of VTE in MI patients is scarcely investigated., Aim: To study the joint effect of MI and obesity on the risk of VTE., Methods: Study participants (n = 29 410) were recruited from three surveys of the Tromsø Study (conducted in 1994-1995, 2001, and 2007-2008) and followed up through 2014. All incident MI and VTE cases during follow-up were recorded. Cox regression models with MI as a time-dependent variable were used to estimate hazard ratios (HRs) of VTE (adjusted for age and sex) by combinations of MI exposure and obesity status. Joint effects were assessed by calculating relative excess risk and attributable proportion (AP) due to interaction., Results: During a median of 19.6 years of follow-up, 2090 study participants experienced an MI and 784 experienced a VTE. Among those with MI, 55 developed a subsequent VTE, yielding an overall incidence rate (IR) of VTE of 5.3 per 1000 person-years (95% confidence interval [CI]: 4.1-6.9). In the combined exposure group (MI+/Obesity+), the IR was 11.3 per 1000 person-years, and the adjusted HR indicated a 3-fold increased risk of VTE (HR 3.16, 95% CI: 1.99-4.99) compared to the reference group (MI-/Obesity-). The corresponding AP was 0.46 (95% CI: 0.17-0.74)., Conclusions: The combination of MI and obesity yielded a supra-additive effect on VTE risk of which 46% of the VTE events were attributed to the interaction., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood. Methods and Results In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all-cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population-based cohorts. During a maximum follow-up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03-2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31-2.34) both significantly increased overall mortality risk. Conclusions We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.

Objectives: The increased survival rate of cardiovascular disease (CVD) implies a higher proportion of individuals who live with CVD. Using data from the Tromsø Study, we aimed to investigate mental health symptom trajectories before and after myocardial infarction, atrial fibrillation or stroke in a general population and to explore factors that contribute to the association., Design: Cohort study., Setting: Sample drawn from inhabitants of the municipality of Tromsø, Norway, who participated in the Tromsø Study (1994-2016)., Participants: A total of 18 719 participants (52.3% women) were included, and of these 2098 (32.9% women) were diagnosed with myocardial infarction, 1896 (41.9% women) with atrial fibrillation and 1263 (42.9% women) with stroke., Primary Outcome Measures: Mental health symptoms were assessed using the Hopkins Symptom Checklist-10 and the Conor Mental Health Index., Results: The participants who were diagnosed with either myocardial infarction or stroke had a significant monotonous increase in mental health symptoms before myocardial infarction (p=0.029) and stroke (p=0.029) that intensified at the time of diagnosis. After the event, the study found a higher prevalence of mental health symptoms with a decline in symptom levels over time for myocardial infarction (p<0.001) and stroke (p=0.004), but not for atrial fibrillation (before: p=0.180, after: p=0.410). The risk of elevated mental health symptoms with myocardial infarction, atrial fibrillation and stroke was associated with sex (p<0.001), age (p<0.01), physical activity (p<0.001), diabetes (p<0.05) and other comorbidities (p<0.001)., Conclusion: The study indicates that mental health problems among individuals with myocardial infarction, atrial fibrillation and stroke may have started to develop several years before the cardiovascular event and suggests that successful CVD rehabilitation may need to consider previous life factors. Future research is recommended to examine whether health promotion measures in a general population also create mental health resilience after a CVD event., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate European guideline treatment target achievement in cardiovascular risk factors, medication use, and lifestyle, after myocardial infarction (MI) or ischaemic stroke, in women and men living in Norway., Methods and Results: In the population-based Tromsø Study 2015-16 (attendance 65%), 904 participants had previous validated MI and/or stroke. Cross-sectionally, we investigated target achievement for blood pressure (<140/90 mmHg, <130/80 mmHg if diabetes), LDL cholesterol (<1.8 mmol/L), HbA1c (<7.0% if diabetes), overweight (body mass index (BMI) <25 kg/m2, waist circumference women <80 cm, men <94 cm), smoking (non-smoking), physical activity (self-reported >sedentary, accelerometer-measured moderate-to-vigorous ≥150 min/week), diet (intake of fruits ≥200 g/day, vegetables ≥200 g/day, fish ≥200 g/week, saturated fat <10E%, fibre ≥30 g/day, alcohol women ≤10 g/day, men ≤20 g/day), and medication use (antihypertensives, lipid-lowering drugs, antithrombotics, and antidiabetics), using regression models. Proportion of target achievement was for blood pressure 55.2%, LDL cholesterol 9.0%, HbA1c 42.5%, BMI 21.1%, waist circumference 15.7%, non-smoking 86.7%, self-reported physical activity 79%, objectively measured physical activity 11.8%, intake of fruit 64.4%, vegetables 40.7%, fish 96.7%, saturated fat 24.3%, fibre 29.9%, and alcohol 78.5%, use of antidiabetics 83.6%, lipid-lowering drugs 81.0%, antihypertensives 75.9%, and antithrombotics 74.6%. Only 0.7% achieved all cardiovascular risk factor targets combined. Largely, there was little difference between the sexes, and in characteristics, medication use, and lifestyle among target achievers compared to non-achievers., Conclusion: Secondary prevention of cardiovascular disease was suboptimal. A negligible proportion achieved the treatment target for all risk factors. Improvement in follow-up care and treatment after MI and stroke is needed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To assess the association between past level of physical activity (PA) and risk for death during the acute phase of myocardial infarction (MI) in a pooled analysis of cohort studies., Methods and Results: European cohorts including participants with a baseline assessment of PA, conventional cardiovascular (CV) risk factors, and available follow-up on MI and death were eligible. Patients with an incident MI were included. Leisure-time PA was grouped as sedentary (<7 MET-hours), low (7-16 MET-hours), moderate (16.1-32 MET-hours), or high (>32 MET-hours) based on calculated net weekly energy expenditure. The main outcome measures were instant and 28-day case fatality of MI. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate random-effects models. Adjustments for age, sex, CV risk factors, alcohol consumption, and socioeconomic status were made. From 10 cohorts including a total of 1 495 254 participants, 28 140 patients with an incident MI comprised the study population. A total of 4976 (17.7%) died within 28 days-of these 3101 (62.3%) were classified as instant fatal MI. Compared with sedentary individuals, those with a higher level of PA had lower adjusted odds of instant fatal MI: low PA [OR, 0.79 (95% CI, 0.60-1.04)], moderate PA [0.67 (0.51-0.89)], and high PA [0.55 (0.40-0.76)]. Similar results were found for 28-day fatal MI: low PA [0.85 (0.71-1.03)], moderate PA [0.64 (0.51-0.80)], and high PA [0.72 (0.51-1.00)]. A low-to-moderate degree of heterogeneity was detected in the analysis of instant fatal MI (I2 = 47.3%), but not in that of 28-day fatal MI (I2 = 0.0%)., Conclusion: A moderate-to-high level of PA was associated with a lower risk of instant and 28-day death in relation to a MI., (© The Author(s) 2021. Published on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3-vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death. Methods and Results We identified 9576 participants in the Tromsø Study (2007-2008) who completed the cold-pressor pain test, and had no prior history of CAD. The median follow-up time was 10.4 years. We applied Cox-regression models with age as time-scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03-1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01-1.47]) adjusted by age as time-scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09-2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19-1.64]). Conclusions Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.

Objectives: The aim of this study was to use the parametric g-formula to estimate the 19-year risk of myocardial infarction (MI) under hypothetical interventions on six cardiovascular risk factors., Design and Setting: A populations-based cohort study with repeated measurements, the Tromsø Study., Primary Outcome Measure: Myocardial infarction., Participants: We estimated the relative and absolute risk reduction under feasible and intensive risk reduction strategies for smoking, physical activity, alcohol drinking, body mass index, total serum cholesterol and systolic blood pressure in 14 965 men and women with 19 years of follow-up (1994-2013)., Results: The estimated 19-year risk of MI under no intervention was 7.5% in individuals with baseline mean age 49.3 years (range 25-69). This risk was reduced by 30% (95% CI 19% to 39%) under joint feasible interventions on all risk factors, and 70% (60%, 78%) under a set of more intensive interventions. The most effective interventions were lowering of total cholesterol to 5.18 mmol/L and lowering of systolic blood pressure to 120 mm Hg (33% and 37% lower MI risk, respectively). The absolute risk reductions were significantly larger in men, in older participants, in smokers and in those with low education., Conclusion: Modification of population levels of cardiovascular risk factors could have prevented close to one-third of the cases of MI in the municipality of Tromsø during 19 years of follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Cardiovascular disease is a common cause of morbidity and mortality, with gender differences in pathophysiology. The endothelial glycocalyx maintains vascular integrity, and glycocalyx shedding reflects endothelial dysfunction and early atherosclerosis. Syndecan-1 and -4 are components of the glycocalyx, and increased serum levels indicate glycocalyx damage. We hypothesised that increased serum syndecan-1 and -4 were independently associated with myocardial infarction (MI), ischaemic stroke and all-cause mortality in men and women from a general population., Methods: Using a case-cohort design, we included 1495 participants from the Tromsø Study 2001-02. Syndecan-1 and -4 were measured in serum. Baseline variables also included age, gender, cardiovascular risk factors and urinary albumin-creatinine ratio (ACR). Hazard ratios were assessed using multivariable Cox regression models., Results: Between baseline in 2001-02 and December 2007 fatal or non-fatal MI was experienced by 328 and ischaemic stroke by 191 subjects, and 423 participants died. Syndecan-4 was independently associated with MI (hazard ratio per 10 ng/mL increase 1.32; 95% confidence interval 1.06-1.63), but not ischaemic stroke and mortality, and the associations were unchanged by adjustment for urinary ACR. Interaction between syndecan-4 and sex was borderline significant, and in gender-specific analysis, syndecan-4 was associated with MI in women only. Syndecan-1 was not associated with any endpoint., Conclusions: Syndecan-4 was associated with incident MI, and the association was stronger in women than in men. This suggests a link between endothelial glycocalyx shedding and coronary heart disease in women. Use of syndecan-4 as a risk marker in clinical setting needs further investigation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Physical activity and overweight are associated with myocardial infarction (MI). However, their joint association with MI remains unclear. Our objective was to examine the independent and joint association between leisure-time physical activity (LTPA), body mass index (BMI) and MI. This prospective cohort study included 16,572 men and women (47.5% women) aged 20-54 years who took part in the second Tromsø Study. At baseline in 1979-80 LTPA was assessed by questionnaire. Data on MI was collected and adjudicated through hospital and causes of death registries between 1979 and 2013. Cox proportional hazards models were used to examine the independent and joint associations between LTPA, BMI and MI. The final sample included 16,104 individuals. During a median follow up of 34 years, 1613 incident cases of MI were recorded. Physical inactivity and elevated BMI were both independently associated with MI (p for trend 0.02 and <0.001). In joint analyses, normal weight, inactive individuals had a 20% higher risk of MI compared to their active counterparts (hazard ratio (HR) 1.20 (1.02-1.41)). The highest risk of MI was seen in obese, inactive individuals when compared to normal weight, active individuals (HR 3.20 (2.30-4.44)). The risk of MI increased with increasing BMI regardless of the activity level. HRs were lower for active compared to inactive individuals within the same BMI category. The findings suggest that LTPA and BMI are independently associated with risk of MI. LTPA seems to attenuate but not eliminate the risk of MI associated with excess bodyweight., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported., Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study., Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994-1995 and 8483 participants (55% women) attending the Tromsø Study 2007-2008 for first-ever MI up to their participation in 2007-2008 and 2015-2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels., Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994-2008 and 2007-2013, respectively. Mean change in total cholesterol was -2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was -1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was -0.33 (95% confidence interval [CI] -0.51 to -0.14) for total cholesterol and -0.21 (95% CI -0.37 to -0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15-2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II., Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.

Background: Unrecognized myocardial infarction (MI) is a frequent condition with unknown underlying reason. We hypothesized the lack of recognition of MI is related to pathophysiology, specifically differences in underlying small and large vessel disease., Methods: 6128 participants were examined with retinal photography, ultrasound of the carotid artery and a 12‑lead electrocardiography (ECG). Small vessel disease was defined as narrower retinal arterioles and/or wider retinal venules measured on retinal photographs. Large vessel disease was defined as carotid artery pathology. We defined unrecognized MI as ECG-evidence of MI without a clinically recognized event. We analyzed the cross-sectional relationship between MI recognition and markers of small and large vessel disease, adjusted for age and sex., Results: Unrecognized MI was present in 502 (8.2%) and recognized MI in 326 (5.3%) of the 6128 participants. Compared to recognized MI, unrecognized MI was associated with small vessel disease indicated by narrower retinal arterioles (OR 1.66, 95% CI 1.05-2.62, highest vs. lowest quartile). Unrecognized MI was less associated with wider retinal venules (OR 0.55, 95% CI 0.35-0.87, lowest vs. highest quartile). Compared to recognized MI, unrecognized MI was less associated with large vessel disease indicated by presence of plaque in the carotid artery (OR for presence of carotid artery plaque in unrecognized MI 0.51, 95% CI 0.37-0.69). No significant sex interaction was present., Conclusions: Unrecognized MI was more associated with small vessel disease and less associated with large vessel disease compared to recognized MI. These findings suggest that the pathophysiology behind unrecognized and recognized MI may differ., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background Unrecognized myocardial infarction (MI) is a frequent and intriguing entity associated with a similar risk of death as recognized MI. Previous studies have not fully addressed whether the poor prognosis is explained by traditional cardiovascular risk factors. We investigated whether electrocardiographically detected unrecognized MI was independently associated with cardiovascular events and death and whether it improved prediction for future MI in a general population. Design Prospective cohort study. Methods We studied 5686 women and men without clinically recognized MI at baseline in 2007-2008. We assessed the risk of future MI, stroke and all-cause mortality in persons with unrecognized MI compared with persons with no MI during 31,051 person-years of follow-up. Results In the unadjusted analyses, unrecognized MI was associated with increased risk of future recognized MI (hazard ratio 1.84, 95% confidence interval (CI) 1.15-2.96) and all-cause mortality (hazard ratio 1.78, 95% CI 1.21-2.61), but not stroke (hazard ratio 1.09, 95% CI 0.56-2.17). The associations did not remain significant after adjustment for traditional risk factors (hazard ratio 1.25, 95% CI 0.76-2.06 and hazard ratio 1.38, 95% CI 0.93-2.05) for MI and all-cause mortality respectively. Unrecognized MI did not improve risk prediction for future recognized MI using the Framingham Risk Score ( p = 0.96) or the European Systematic COronary Risk Evaluation ( p = 0.65). There was no significant sex interaction regarding any of the endpoints. Conclusion Electrocardiographic unrecognized MI was not significantly associated with future risk of MI, stroke or all-cause mortality in the general population after adjustment for the traditional cardiovascular risk factors, and it did not improve prediction of future MI.

Background and Aims: Overall, men have roughly twice the risk of myocardial infarction (MI) compared to women, but what causes this contrast is unclear. Identification of subgroups where the gender contrast in risk is particularly low or high, may provide new insight. In the search for such subgroups, we focus on gender-specific effects of established coronary heart disease (CHD) risk factors. Heterogeneity across age groups is also explored., Methods: Population-based prospective study from Tromsø, Norway, comprising 33,859 individuals (51% women); 2746 individuals (854 women) received a diagnosis of MI during follow-up at ages 35-94 years. Incidence rate ratios (IRR) were calculated as estimates of relative risk in Poisson regression analyses., Results: The association between total cholesterol and risk of MI was stronger for men than women, and IRR for men vs. women accordingly increased with increasing cholesterol, but the risk was higher for men in all subgroups (IRR in range 1.63-3.27), except among older people with low cholesterol levels. The adverse effect of increasing blood pressure (BP) was stronger for women, and IRR for gender diminished with increasing systolic (from 3.90 to 1.38) and diastolic BP (from 2.87 to 1.54). The gender contrast in risk was also substantially reduced in smokers ≥75 years. Associations with high-density lipoprotein cholesterol (HDL-C) did not differ between genders., Conclusions: Gender heterogeneity in associations with total cholesterol but not HDL-C indicates gender differences in associations with non-HDL-C. The stronger association with BP in women may relate to more severe hypertension-induced left ventricular hypertrophy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background Resting heart rate is an established risk factor for cardiovascular disease, but long-term individual resting heart rate trajectories and their effect on cardiovascular disease morbidity and mortality have not yet been described. Methods This large population-based longitudinal study included 14,208 men and women aged 20 years or older, not pregnant and not using blood pressure medications, who attended at least two of the three Tromsø Study surveys conducted between 1986-2001. Resting heart rate was measured using an automated Dinamap device. Participants were followed up from 2001 to 2012 with respect to myocardial infarction, atrial fibrillation, ischaemic stroke, cardiovascular disease death and total death. The Proc Traj statistical procedure was used to identify resting heart rate trajectories. Results Five common long-term resting heart rate trajectories were identified: low, moderate, decreasing, increasing and elevated. In men, an elevated resting heart rate trajectory was independently associated with an increased risk of myocardial infarction when low resting heart rate trajectory was used as a reference (hazard ratio 1.83, 95% confidence interval 1.11-3.02). Risk of total death in men was lowest in the low resting heart rate trajectory group and highest in the increasing and elevated resting heart rate trajectory groups. In women, the association between resting heart rate trajectories and myocardial infarction was similar to that in men, but it was not significant. Conclusions Among the five long-term resting heart rate trajectories we identified, increasing and elevated trajectories were associated with an increased risk of myocardial infarction and total death in men. Our results suggest that changes in long-term individual resting heart rate in the general population may provide additional prognostic information.

The association between myocardial infarction (MI) and future risk of incident cancer is scarcely investigated. Therefore, we aimed to study the risk of cancer after a first time MI in a large cohort recruited from a general population. Participants in a large population-based study without a previous history of MI or cancer (n = 28,763) were included and followed from baseline to date of cancer, death, migration or study end. Crude incidence rates (IRs) and hazard ratios (HRs) for cancer after MI were calculated. During a median follow-up of 15.7 years, 1747 subjects developed incident MI, and of these, 146 suffered from a subsequent cancer. In the multivariable-adjusted model (adjusted for age, sex, BMI, systolic blood pressure, diabetes mellitus, HDL cholesterol, smoking, physical activity and education level), MI patients had 46% (HR 1.46; 95% CI: 1.21-1.77) higher hazard ratio of cancer compared to those without MI. The increased cancer incidence was highest during the first 6 months after the MI, with a 2.2-fold higher HR (2.15; 95% CI: 1.29-3.58) compared with subjects without MI. After a 2-year period without higher incidence rate, MI patients displayed 60% (HR 1.60; 95% CI: 1.27-2.03) higher HR of future cancer more than 3 years after the event. The increased IRs were higher in women than men. Patients with MI had a higher short- and long-term incidence rate of cancer compared to subjects without MI. Our findings suggest that occult cancer and shared risk factors of MI and cancer may partly explain the association.

Importance: 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., Objective: To quantify the difference in risk of incident myocardial infarction (MI) between men and women., Design, Setting and Participants: 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., Exposures: Sex, age, birth cohort, serum lipid levels, blood pressure, lifestyle factors, diabetes., Main Outcomes and Measures: Incident MI., Results: 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., Conclusions and Relevance: 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.

Background: Single measurements of modifiable risk factors may underestimate associations with outcomes in cohorts. We aimed to compare risk estimates of myocardial infarction (MI) and venous thromboembolism (VTE) by atherosclerotic risk factors during long follow-up using time-fixed analyses without and with correction for regression dilution and time-varying analyses., Methods: The study included 5970 subjects enrolled in the fourth survey of the Tromsø Study (1994/95). Blood pressure, lipid levels, body mass index (BMI), diabetes and smoking status were measured at baseline, and subjects still alive at the fifth (2001/02, n = 5179) and sixth (2007/08, n = 4391) survey were re-measured. Incident events of MI (n = 714) and VTE (n = 214) were recorded until December 2010. Time-fixed and time-varying Cox regression models were used to estimate hazard ratios (HR) for MI and VTE adjusted for age and sex., Results: Variations in BMI, blood pressure and lipid levels were small, and did not alter the risk estimates when time-varying analyses were compared to time-fixed analyses. For MI, variables that changed considerably over time yielded the greatest changes in risk estimates (HR for smoking changed from 1.80 (95% CI 1.55-2.10) to 2.08 (95% CI 1.78-2.42)). For VTE, only BMI was associated with increased risk in both time-fixed and time-varying analysis, but the risk estimates weakened in the time-varying analysis. Correction of time-fixed HRs with Rosner´s method tended to overestimate risk estimates compared to time-varying analysis., Comment: For MI and VTE, risk estimates based on baseline and repeated measures corresponded well, whereas correction for regression dilution tended to overestimate risks., Competing Interests: The authors have declared that no competing interests exist.

Background: Elevated resting heart rate (RHR) increases risk of death overall, but a comprehensive picture of the associations between RHR, cardiovascular morbidity and mortality events has not yet been presented. We aimed to investigate the effect of RHR on the risk of 5 cardiovascular events: incident myocardial infarction (MI), incident atrial fibrillation (AF), incident ischaemic stroke, total death and cardiovascular death in a general population from Norway., Methods: We followed 24 489 men and women from the Tromsø Study 1994-1995, a population-based cohort study, for 18 years, and analysed the association between RHR and the investigated cardiovascular events. Sex-specific Cox regression with time-dependent covariates was applied with the best-fitting fractional polynomials of RHR., Results: Among men, an independent positive relationship was observed for MI and AF (adjusted HR for AF per 20 bpm increase=1.14; 95% CI 1.02 to 1.27). In women, the corresponding HR for MI was 1.23 (1.09 to 1.40). A J-shaped association was observed for ischaemic stroke in women when compared with a RHR of 70 bpm (HR for 50 bpm=1.31; 0.90 to 1.90; HR for 100 bpm=1.32; 1.04 to 1.69). Total and cardiovascular death showed a strong positive association with RHR in men. In women, the pattern for total death was similar., Conclusions: RHR is an independent risk factor for several cardiovascular events. A novel finding is the positive association between RHR and AF in men and the sex difference in association with ischaemic stroke., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Though the associations between low serum 25-hydroxyvitamin D (25(OH)D) levels and health outcomes such as type 2 diabetes (T2D), myocardial infarction (MI), cancer, and mortality are well-studied, the effect of supplementation with vitamin D is uncertain. This may be related to genetic differences. Thus, rs7968585, a single nucleotide polymorphism (SNP) of the vitamin D receptor (VDR), has recently been reported as a predictor of composite health outcome. We therefore aimed to evaluate whether rs7968585 predicts separate clinical outcomes such as T2D, MI, cancer, and mortality in a community-based Norwegian population., Methods and Findings: Measurements and DNA were obtained from the participants in the Tromsø Study in 1994-1995, registered with the outcomes of interest and a randomly selected control group. The impact of the rs7968585 genotypes was evaluated with Cox proportional hazards. A total of 8,461 subjects were included among whom 1,054 subjects were registered with T2D, 2,287 with MI, 3,166 with cancer, and 4,336 with death. Mean follow-up time from birth was 60.8 years for T2D and MI, 61.2 years for cancer, while mean follow-up time from examination date was 16.5 years for survival. Mean serum 25(OH)D levels did not differ across the rs7968585 genotypes. With the major homozygote genotype as reference, the minor homozygote subjects had hazard ratios of 1.25 (95% CI 1.05-1.49) for T2D and 1.14 (1.02-1.28) for MI (P = 0.011 and 0.023, respectively, without the Bonferroni correction). No significant interaction between serum 25(OH)D status and the rs7968585 genotype was found for any of the endpoints., Conclusions: The VDR-related SNP rs7968585 minor allele is a significant and positive predictor for T2D and possibly for MI. Since the functional mechanism of this SNP is not yet understood, and the association with T2D is reported for the first time, confirmatory studies are needed.

Background: Identification of individuals with high risk for first-ever myocardial infarction (MI) can be improved. The objectives of the study were to survey multiple protein biomarkers for association with the 10-year risk of incident MI and identify a clinically significant risk model that adds information to current common risk models., Methods and Results: We used an immunoassay platform that uses 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 case control design was used with 419 first-ever MI cases (169 females/250 males) and 398 controls (244 females/154 males). Of the proteins measured, 17 were predictors of MI when considered individually after adjustment for traditional risk factors either in men, women, or both. The 6 biomarkers adjusted for traditional risk factors that were selected in a multivariable model (odds ratios [OR] per standard deviation) using a stepwise procedure were apolipoprotein B/apolipoprotein A1 ratio (1.40), kallikrein (0.73), lipoprotein a (1.29), matrix metalloproteinase 9 (1.30), the interaction term IP-10/CXCL10×women (0.69), and the interaction term thrombospondin 4×men (1.38). The composite risk of these biomarkers added significantly to the traditional risk factor model with a net reclassification improvement of 14% (P=0.0002), whereas the receiver operating characteristic area increased from 0.757 to 0.791, P=0.0004., Conclusions: Novel protein biomarker models improve identification of 10-year MI risk above and beyond traditional risk factors with 14% better allocation to either high or low risk group., (© 2015 American Heart Association, Inc.)

Background: The American Heart Association has proposed an impact goal for the year 2020 to improve cardiovascular health by 20%. The objectives of the study were to assess the association between the proposed cardiovascular health metric score and incident myocardial infarction (MI) and to estimate the generalized impact fraction (GIF)., Methods: The health metric score was derived from ideal levels of six cardiovascular risk factors from the population-based Tromsø Study of 22,121 residents of Tromsø, Norway aged 30 to 79 years, examined in 1994-95, 2001, and 2007-08. Incident events of MI were recorded from the date of enrollment in 1994-95 to the end of 2010. Adjudication of hospitalized and out-of hospital events was performed by an independent endpoints committee based on data from hospital and out-of hospital journals, autopsy records and death certificates. Cox proportional hazard regression was used to estimate hazard ratios (HR). GIF was calculated from age stratified analysis using a case-load weighted-sum method. Bootstrapping was used to estimate 95% simulation intervals., Results: A total of 1652 MIs accrued over an average of 14.7 person-years of follow-up. Few men (0.96%) and women (3.6%) had ideal levels in all 6 metrics. 64.7% (men) and 55.7% (women) had ideal levels in 2 or 3 metrics. The age-adjusted HR per point increase in health score was 0.65 (95% confidence interval: 0.61, 0.70) in men and 0.59 (0.54, 0.64) in women. A shift of 30% of subjects from low score levels ≤3 to scores ≥4 was estimated to prevent 13.7% (11.2, 16.2) of incident MI in men and 15.9% (12.1, 19.4) in women., Conclusions: The association between the health metric score and MI indicate that close to 15% of incident MIs could be prevented by attainable and realistic improvements in the health metrics.

Genome-wide association studies have identified variants, primarily common, that are associated with coronary artery disease or myocardial infarction (MI), but have not tested the majority of the low frequency and rare variation in the genome. We explored the hypothesis that previously untested low frequency (1-5% minor allele frequency) and rare (<1% minor allele frequency) coding variants are associated with MI. We genotyped 2906 MI cases and 6738 non-MI controls from Norway using the Illumina HumanExome Beadchip, allowing for direct genotyping of 85 972 polymorphic coding variants as well as 48 known GWAS SNPs. We followed-up 34 coding variants in an additional 2350 MI cases and 2318 controls from Norway. We evaluated exome array coverage in a subset of these samples using whole exome sequencing (N = 151). The exome array provided successful genotyping for an estimated 72.5% of Norwegian loss-of-function or missense variants with frequency >1% and 66.2% of variants <1% frequency observed more than once. Despite 80% power in the two-stage study (N = 14 312) to detect association with low-frequency variants with high effect sizes [odds ratio (OR) >1.86 and >1.36 for 1 and 5% frequency, respectively], we did not identify any novel genes or single variants that reached significance. This suggests that low-frequency coding variants with large effect sizes (OR >2) may not exist for MI. Larger sample sizes may identify coding variants with more moderate effects., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Red cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, is associated with mortality and adverse outcome in selected populations with cardiovascular disease. It is scarcely known whether RDW is associated with incident myocardial infarction (MI). We aimed to investigate whether RDW was associated with risk of first-ever MI in a large cohort study with participants recruited from a general population., Methods and Results: Baseline characteristics, including RDW, were collected for 25 612 participants in the Tromsø Study in 1994-1995. Incident MI during follow-up was registered from inclusion through December 31, 2010. Cox regression models were used to calculate hazard ratios with 95% confidence intervals for MI, adjusted for age, sex, body mass index, smoking, hemoglobin, white blood cells, platelets, and other traditional cardiovascular risk factors. A total of 1779 participants experienced a first-ever MI during a median follow-up time of 15.8 years. There was a linear association between RDW and risk of MI, for which a 1% increment in RDW was associated with a 13% increased risk (hazard ratio 1.13; 95% CI, 1.07 to 1.19). Participants with RDW above the 95th percentile had 71% higher risk of MI compared with those with RDW in the lowest quintile (hazard ratio 1.71; 95% CI, 1.34 to 2.20). All effect estimates were essentially similar after exclusion of participants with anemia (n=1297) from the analyses., Conclusion: RDW is associated with incident MI in a general population independent of anemia and cardiovascular risk factors., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 × 10(-8)). One variant in TM6SF2 (encoding p.Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.

Objective: Recent studies have suggested that arterial and venous thrombosis share common risk factors. Although carotid atherosclerosis is associated with arterial cardiovascular events, its role in venous thromboembolic disease is unclear. We wanted to investigate and compare the effect of carotid atherosclerosis on the risk of myocardial infarction (MI) and venous thromboembolism (VTE) in a general population, taking into account competing risks., Approach and Results: Mean intima-media thickness and total plaque area in the right carotid artery were measured with ultrasound in 6257 people aged 25 to 84 years who participated in a population-based health study, the Tromsø Study, from 1994 to 1995. Incident MI and VTE events were registered from date of enrollment to end of follow-up on December 31, 2010. Cox proportional hazards regression models using age as time scale were used to estimate cause-specific hazard ratios with 95% confidence intervals for MI and VTE by increasing levels of intima-media thickness and total plaque area. There were 894 incident MI cases and 256 VTE events during a median of 15.4 years of follow-up. The risk of MI increased significantly across quartiles of mean intima-media thickness (P for trend <0.001) and with increasing total plaque area (P for trend <0.001), but neither intima-media thickness (P for trend=0.94) nor total plaque area (P for trend=0.45) was associated with VTE risk in multivariable-adjusted analysis., Conclusions: In this study, carotid atherosclerosis was strongly associated with future MI but not with VTE. Our findings suggest that carotid atherosclerosis does not represent a link between arterial and venous thrombosis.

Active smoking is a well-established risk factor for myocardial infarction, but less is known about the impact of passive smoking, and possible sex differences in risk related to passive smoking. We investigated active and passive smoking as risk factors for myocardial infarction in an 11-year follow-up of 11,762 men and 13,206 women included in the Tromsø Study. There were a total of 769 and 453 incident cases of myocardial infarction in men and women, respectively. We found linear age-adjusted relationships between both active and passive smoking and myocardial infarction incidence in both sexes. The relationships seem to be stronger for women than for men. Age-adjusted analyses indicated a stronger relationship with passive smoking in ever-smokers than in never-smokers. After adjustment for important confounders (body mass index, blood pressure, total cholesterol, HDL cholesterol and physical activity) the associations with active and passive smoking were still statistically significant. Adjusting for active smoking when assessing the effect of passive smoking and vice versa, indicated that the effect of passive smoking in men may be explained by their own active smoking. In women, living with a smoker ≥30 years after the age of 20 increased the myocardial infarction risk by 40 %, even after adjusting for active smoking. Passive smoking is a risk factor for myocardial infarction on its own, but whereas the effect for men seems to be explained by their own active smoking, the effect in females remains statistically significant.

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 2.50-2.60 mmol/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 2.20-2.29 mmol/L. For rs17251221 there was a mean difference in serum calcium of 0.05 mmol/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.

Background: Although the mortality of coronary heart disease (CHD) has declined in Western countries during the last decades, studies have suggested that the prevention and treatment of CHD may not have been as effective in women as in men. We examined gender- and age-specific trends in incidence, case fatality and the severity of first myocardial infarction (MI) in a large Norwegian population-based study., Design: Prospective population-based cohort study., Methods: A total of 31,323 participants enrolled between 1974 and 2001 were followed throughout 2004 for a total of 400,572 person-years. Suspected coronary events were adjudicated by a review of hospital records and death certificates. A total of 1669 events fulfilled standardized criteria of first-ever fatal or non-fatal MI., Results: In the age group 35-79 years, the age-adjusted incidence of MI declined significantly in men, whereas an increase was observed in women. For men and women ≥ 80 years the incidence rates remained unchanged. The severity of MI and the 28-day and 1-year case fatality rates declined significantly and similarly in men and women., Conclusion: Trends in MI incidence differed by sex and age; in the age group 35-79 years a marked decrease was observed among men but an increase was observed among women, while no change was observed among older patients. MI severity and case fatality were clearly reduced for both sexes. These data suggest that the burden of CHD is shifting from middle-aged men toward middle-aged women and elderly patients.

Introduction: The relationship between QT interval and cardiovascular disease is controversial., Methods: All male residents aged 20-61 years and female residents aged 20-56 years were invited to the Tromsø Study in 1986-1987. A total of 15,558 participants free of heart disease were prospectively followed over 20 years for myocardial infarction and death. QT interval at baseline was measured on lead I of the electrocardiogram. Hazard ratios (HRs) with 95% confidence intervals (CIs) per standard deviation change in QT interval were calculated using a Cox regression model., Results: We identified 756 cases of myocardial infarction and 1,183 all-cause deaths. Prolonged QT interval was present in 792 (5%) participants. QT interval was not associated with increased risk of myocardial infarction (HR: 0.95, 95% CI: 0.84-1.07, after adjustment for potential confounders). Heart-rate-corrected QT interval was a significant predictor for all-cause death in men (HR: 1.15, 95% CI: 1.03-1.29), but not in women (HR: 1.04, 95% CI: 0.91-1.18), after adjustment for potential confounders., Conclusions: The findings suggest that the previously observed relationship between QT interval and increased risk of cardiovascular death is not mediated by increased risk of myocardial infarction. The clinical utility of the QT interval to identify individuals at high risk for coronary events is limited in a general population without prior heart disease., (© 2011 Wiley Periodicals, Inc.)

Objective: Low serum 25(OH)D levels are associated with cardiovascular risk factors, and also predict future myocardial infarction (MI), type 2 diabetes (T2DM), cancer and all-cause mortality. Recently several single nucleotide polymorphisms (SNPs) associated with serum 25-hydroxyvitamin D (25(OH)D) level have been identified. If these relations are causal one would expect a similar association between these SNPs and health., Methods: DNA was prepared from subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death as well as a randomly selected control group. The endpoint registers were complete up to 2007-2010. Genotyping was performed for 17 SNPs related to the serum 25(OH)D level., Results: A total of 9528 subjects were selected for genetic analyses which were successfully performed for at least one SNP in 9471 subjects. Among these, 2025 were registered with MI, 1092 with T2DM, 2924 with cancer and 3828 had died. The mean differences in serum 25(OH)D levels between SNP genotypes with the lowest and highest serum 25(OH)D levels varied from 0.1 to 7.8 nmol/L. A genotype score based on weighted risk alleles regarding low serum 25(OH)D levels was established. There was no consistent association between the genotype score or individuals SNPs and MI, T2DM, cancer, mortality or risk factors for disease. However, for rs6013897 genotypes (located at the 24-hydroxylase gene (CYP24A1)) there was a significant association with breast cancer (P<0.05)., Conclusion: Our results do not support nor exclude a causal relationship between serum 25(OH)D levels and MI, T2DM, cancer or mortality, and our observation on breast cancer needs confirmation. Further genetic studies are warranted, particularly in populations with vitamin D deficiency., Trial Registration: ClinicalTrials.gov NCT01395303.

Background: A seasonal pattern with higher winter morbidity and mortality has been reported for acute myocardial infarction (MI). The magnitude of the difference between peak and nadir season has been associated with latitude, but results are inconsistent. Studies of seasonal variation of MI in population-based cohorts, based on adjudicated MI cases,are few.We investigated the monthly and seasonal variation in first-ever nonfatal and fatal MI in the population of Tromsø in northern Norway, a region with a harsh climate and extreme seasonal variation in daylight exposure., Design: Prospective population-based cohort study., Methods: A total of 37 392 participants from the Tromsø Study enrolled between 1974 and 2001 were followed throughout 2004. Each incident case of MI was validated by the review of medical records and death certificates. MI incidence rates for months and seasons were analyzed for seasonal patterns with Poisson regression and the Cosinor procedure. All analyses were stratified by sex, age and smoking status., Results: A total of 1893 first-ever MIs were registered, of which 592 were fatal. There was an 11 % (95% confidence interval: 1.00-1.23, P=0.04) increased risk of incident MI during winter (November-January) compared with non-winter seasons, with no statistically significant interaction with sex, age, smoking or calendar year. Other seasonal modelling gave similar but not statistically significant results., Conclusion: We found a small increase in risk of incident MI during the darkest winter months. Populations living in sub-Arctic areas may be adapted to face climate exposure during winter through behavioural protection.

Objective: To develop a cardiovascular risk model simulating different clinical settings using a staged approach., Design: Using data from 27,477 men and women from the Norwegian Tromsø Study in 1986-1987 and 1994-1995, Cox regression models for either myocardial infarction (MI) or stroke combined with a similar model for the competing event a risk model that assess ten-year risk of MI and stroke was developed. Explanatory variables (questions, simple examinations and blood samples) were added gradually. The model was validated using Hosmer-Lemeshow test, the Brier score, c-index, integrated discrimination improvement (IDI) and Net Reclassification Improvement (NRI)., Results: In total, 1,298 events of MI and 769 events of stroke were registered. For MI the model showed excellent discrimination in each step with c-index from 0.833 to 0.946. For stroke the c-index ranged between 0.817 and 0.898. IDI showed significant increases in discrimination. The Brier scores and goodness of fit test showed well calibrated models in all steps for all sex- and end-point specific models (p>0.05)., Conclusions: Although the predictive and discriminative ability of the models increased with each step, even the simplest model containing only data from questions or blood samples alone yielded valid estimates of cardiovascular risk.

Aim: Increased urinary albumin-excretion is a cardiovascular risk-factor. The cardiovascular risk of the metabolic syndrome (MetS) is debated. The aim of the present prospective, population-based study of non-diabetic individuals was to examine the association between low-grade urinary albumin-excretion, MetS, and cardiovascular morbidity and all-cause mortality., Methods: 5215 non-diabetic, non-proteinuric men and women participating in the Tromsø Study 1994-1995 were included. Urinary albumin-creatinine ratio (ACR) was measured in three urine samples. The participants were categorized into four groups by the presence/absence of MetS (the International Diabetes Federation definition) and ACR in the upper tertile (>or=0.75 mg/mmol)., Results: Median follow-up time was 9.6 years for first ever myocardial infarction, 9.7 years for ischemic stroke and 12.4 years for mortality. High ACR (upper tertile)/MetS was associated with increased risk of myocardial infarction (hazard ratio (HR) 1.75; 95% confidence interval (CI): 1.30-2.37, p<0.001), stroke (HR 2.48; 95% CI: 1.66-3.71, p<0.001), and all-cause mortality (HR 1.63; 95% CI: 1.32-2.01, p<0.001) compared to reference (low ACR/no MetS). Similar associations were found for the high ACR/no MetS group. Low ACR/MetS was associated with myocardial infarction only (HR 1.82; 95% CI: 1.39-2.37, p<0.001). MetS predicted neither stroke nor mortality. Adjusted for its individual components, MetS was not associated with any end-point., Conclusions: ACR>or=0.75 mg/mmol was associated with cardiovascular morbidity and all-cause mortality independently of MetS. MetS was not associated with any end-point beyond what was predicted from its components. Thus, low-grade albuminuria, but not MetS, may be used for risk stratification in non-diabetic subjects.

Background and Purpose: Ultrasound of carotid arteries provides measures of intima media thickness (IMT) and plaque, both widely used as surrogate measures of cardiovascular disease. Although IMT and plaques are highly intercorrelated, the relationship between carotid plaque and IMT and cardiovascular disease has been conflicting. In this prospective, population-based study, we measured carotid IMT, total plaque area, and plaque echogenicity as predictors for first-ever myocardial infarction (MI)., Methods: IMT, total plaque area, and plaque echogenicity were measured in 6226 men and women aged 25 to 84 years with no previous MI. The subjects were followed for 6 years and incident MI was registered., Results: During follow-up, MI occurred in 6.6% of men and 3.0% of women. The adjusted relative risk (RR; 95% CI) between the highest plaque area tertile versus no plaque was 1.56 (1.04 to 2.36) in men and 3.95 (2.16 to 7.19) in women. In women, there was a significant trend toward a higher MI risk with more echolucent plaque. The adjusted RR (95% CI) in the highest versus lowest IMT quartile was 1.73 (0.98 to 3.06) in men and 2.86 (1.07 to 7.65) in women. When we excluded bulb IMT from analyses, IMT did not predict MI in either sex., Conclusions: In a general population, carotid plaque area was a stronger predictor of first-ever MI than was IMT. Carotid atherosclerosis was a stronger risk factor for MI in women than in men. In women, the risk of MI increased with plaque echolucency.

Background The role of serum uric acid as an independent predictor of cardiovascular disease and death is uncertain in the general population. Adjustments for additional cardiovascular risk factors have not been consistent. We examined the association of serum uric acid with all-cause mortality, ischemic stroke and myocardial infarction in a prospective population based study, with several traditional and non-traditional risk factors for cardiovascular disease included in the model. Methods A population-based prospective cohort study was performed among 2696 men and 3004 women. Endpoints were all-cause mortality after 15 years, and fatal or non-fatal myocardial infarction (MI) and ischemic stroke after 12 years. Results 1433 deaths, 659 MIs and 430 ischemic strokes occurred during follow-up. Fully adjusted Cox regression analyses showed that per 1 SD (87 μmol/L) increase in serum uric acid level, the risk of all-cause mortality increased in both genders (hazard ratios, HR men; 1.11, 95% CI 1.02-1.20, women; 1.16, 1.05-1.29). HRs and 95% CI for stroke were 1.31, 1.14-1.50 in men, 1.13, 0.94-1.36 in women, and 1.22 (1.09, 1.35) in the overall population. No independent associations were observed with MI. Conclusion Serum uric acid was associated with all-cause mortality in men and women, even after adjustment for blood pressure, estimated GFR, urinary albumin/creatinine ratio, drug intake and traditional cardiovascular risk factors. After the same adjustments, serum uric acid was associated with 31% increased risk of stroke in men. [ABSTRACT FROM AUTHOR]

Background Glomerular filtration rate <60 mL/min/1.73m2 is associated with increased cardiovascular risk. Cystatin C is believed to be a better tool than creatinine for detection of mild renal dysfunction (>60 mL/min/1.73m2) and possibly a more sensitive marker for cardiovascular risk and all-cause mortality. We examined the association of cystatin C with cardiovascular morbidity and all-cause mortality in a prospective population-based study. Methods Cystatin C was measured in 2852 men and 3153 women in the Tromsø Study 1994/95. Gender-specific associations during 12 years of follow-up for all-cause mortality and 9.5 years for myocardial infarction (MI) and ischaemic stroke were assessed (Cox proportional hazard ratios, HRs). Results During follow-up, 591 MIs, 293 ischaemic strokes and 1262 deaths occurred. In women, HR for all-cause mortality was increased in the upper cystatin C quartile (≥0.93 mg/L) compared with the lowest quartile (≤0.73 mg/L); 1.38, 95% confidence interval 1.04–1.84. A significant interaction with gender was observed. One SD (0.17 mg/L) increase in cystatin C was associated with 9% higher risk of death in women, also when persons with a cancer history were excluded. Crude HRs for MI and ischaemic stroke were increased in both genders, but the associations did not persist after multivariable adjustments. No independent associations with end points were observed in non-gender-specific analyses. Conclusions Cystatin C was not independently associated with fatal and non-fatal MI or ischaemic stroke in the general population. However, cystatin C was a risk factor for all-cause mortality in women. [ABSTRACT FROM PUBLISHER]

Introduction: Diabetes is associated with increased risk of coronary heart disease (CHD). The relative risk has been found to be higher in women than men, and the more pronounced adverse effect has even been claimed to eliminate the female advantage in risk. However, few previous studies have quantified the difference in risk between men and women among individuals with diabetes. Aims: To evaluate interaction between gender and diabetes in relation to the risk of incident myocardial infarction (MI). Methods: Population-based prospective study of 33,859 individuals (51% women) in Tromsø, Norway. Median follow-up time at ages 35-94 years was 17.6 years; 2,746 individuals (854 women) were diagnosed with MI during follow-up. At their last visit, a total of 1063 individuals (3.1%) reported they had diabetes (530 men, 533 women); 170 (74 women) were later diagnosed with MI. Incidence rate ratios (IRR) were calculated as estimates of relative risk in Poisson regression analysis of person-years at risk. Interaction terms were included in the model to evaluate heterogeneity in risk estimates across subgroups. Results: Adjusted for age, gender and established CHD risk factors, diabetes was associated with a doubling in risk of MI (IRR=2.18, 95% CI=1.86-2.55). The adverse effect was slightly more pronounced for women than men (IRR of 2.55 vs. 1.96, p=0.11, test for interaction). Accordingly, the gender contrast in risk was less pronounced among individuals with diabetes (IRR of 1.63 vs 2.11), but the elevated risk in men remained significant. Considering combined categories of interacting factors, women with diabetes had a risk level close to men without diabetes, but men with diabetes had a risk about four times as high as women without diabetes. Some heterogeneity across age groups was seen, but risk estimates were imprecise. These results are preliminary. Gender heterogeneity in associations with adjustment factors may influence risk estimates. Analyses based on data with 5 year extended follow-up are planned. Conclusions: In terms of relative risk, the association between diabetes and risk of MI was more pronounced for women than men, but the female advantage in risk of MI was not erased in persons with diabetes. [ABSTRACT FROM AUTHOR]

Background: Few studies have used individual person data to study whether contemporary trends in the incidence of coronary heart disease are associated with changes in modifiable coronary risk factors.Methods and Results: We identified 29 582 healthy men and women ≥25 years of age who participated in 3 population surveys conducted between 1994 and 2008 in Tromsø, Norway. Age- and sex-adjusted incidence rates were calculated for coronary heart disease overall, out-of-hospital sudden death, and hospitalized ST-segment-elevation and non-ST-segment-elevation myocardial infarction. We measured coronary risk factors at each survey and estimated the relationship between changes in risk factors and changes in incidence trends. A total of 1845 participants had an incident acute coronary heart disease event during 375 064 person-years of follow-up from 1994 to 2010. The age- and sex-adjusted incidence of total coronary heart disease decreased by 3% (95% confidence interval, 2.0-4.0; P<0.001) each year. This decline was driven by decreases in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in coronary risk factors accounted for 66% (95% confidence interval, 48-97; P<0.001) of the decline in total coronary heart disease. Favorable changes in cholesterol contributed 32% to the decline, whereas blood pressure, smoking, and physical activity each contributed 14%, 13%, and 9%, respectively.Conclusions: We observed a substantial decline in the incidence of coronary heart disease that was driven by reductions in out-of-hospital sudden death and hospitalized ST-segment-elevation myocardial infarction. Changes in modifiable coronary risk factors accounted for 66% of the decline in coronary heart disease events. [ABSTRACT FROM AUTHOR]