Females Display Lower Risk of Myocardial Infarction From Higher Estimated Cardiorespiratory Fitness Than Males: The Tromsø Study 1994-2014.

Objective: To examine the dose-response association between estimated cardiorespiratory fitness (eCRF) and risk of myocardial infarction (MI). Patients and Methods: Adults who attended Tromsø Study surveys 4-6 (Janurary 1,1994-December 20, 2008) with no previous cardiovascular disease were followed up through December 31, 2014 for incident MI. Associations were examined using restricted cubic splines Fine and Gray regressions, adjusted for education, smoking, alcohol, diet, sex, adiposity, physical activity, study survey, and age (timescale) in the total cohort and subsamples with hyperlipidemia (n=2956), hypertension (n=8290), obesity (n=5784), metabolic syndrome (n=1410), smokers (n=3823), and poor diet (n=3463) and in those who were physically inactive (n=6255). Results: Of 14,285 participants (mean age ± SD, 53.7±11.4 years), 979 (6.9%) experienced MI during follow-up (median, 7.2 years; 25th-75th, 5.3-14.6 years). Females with median eCRF (32 mL/kg/min) had 43% lower MI risk (subdistributed hazard ratio [SHR], 0.57; 95% CI, 0.48-0.68) than those at the 10th percentile (25 mL/kg/min) as reference. The lowest MI risk was observed at 47 mL/kg/min (SHR, 0.02; 95% CI, 0.01-0.11). Males had 26% lower MI risk at median eCRF (40 mL/kg/min; SHR, 0.74; 95% CI, 0.63-0.86) than those at the 10th percentile (32 mL/kg/min), and the lowest risk was 69% (SHR, 0.31; 95% CI, 0.14-0.71) at 60 mL/kg/min. The associations were similar in subsamples with cardiovascular disease risk factors. Conclusion: Higher eCRF associated with lower MI risk in females and males, but associations were more pronounced among females than those in males. This suggest eCRF as a vital estimate to implement in medical care to identify individuals at high risk of future MI, especially for females.

Sex-specific time trends in incident atrial fibrillation and the contribution of risk factors: the Tromsø Study 1994-2016.

AIMS: To explore sex-specific time trends in atrial fibrillation (AF) incidence and to estimate the impact of changes in risk factor levels using individual participant-level data from the population-based Tromsø Study 1994-2016. METHODS AND RESULTS: A total of 14 818 women and 13 225 men aged 25 years or older without AF were enrolled in the Tromsø Study between 1994 and 2008 and followed up for incident AF throughout 2016. Poisson regression was used for statistical analyses. During follow-up, age-adjusted AF incidence rates in women decreased from 1.19 to 0.71 per 1000 person-years. In men, AF incidence increased from 1.18 to 2.82 per 1000 person-years in 2004, and then declined to 1.94 per 1000 person-years in 2016. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), physical activity, smoking and alcohol consumption together accounted for 10.9% [95% confidence interval (CI): -2.4 to 28.6] of the AF incidence decline in women and for 44.7% (95% CI: 19.2; 100.0) of the AF incidence increase in men. Reduction in SBP and DBP had the largest contribution to the decrease in AF incidence in women. Increase in BMI had the largest contribution to the increase in AF incidence in men. CONCLUSION: In the population-based Tromsø Study 1994-2016, AF incidence decreased in women and increased following a reverse U-shape in men. Individual changes in SBP and DBP in women and individual changes in BMI in men were the most important risk factors contributing to the AF incidence trends.

Lifestyle factors as mediators of area-level socio-economic differentials in cardiovascular disease risk factors. The Tromsø Study.

Introduction: Cardiovascular disease (CVD) is a leading cause of death and disability and living in areas with low socio-economic status (SES) is associated with increased risk of CVD. Lifestyle factors such as smoking, physical inactivity, an unhealthy diet and harmful alcohol use are main risk factors that contribute to other modifiable risk factors, such as hypertension, raised blood cholesterol, obesity, and diabetes. The potential impact of area-level socio-economic status (ASES) on metabolic CVD risk factors via lifestyle behaviors independent of individual SES has not been investigated previously. Aims: To estimate associations of ASES with CVD risk factors and the mediating role of lifestyle behaviors independent of individual-level SES. Methods: In this cross-sectional study, we included 19,415 participants (52% women) from the seventh survey of the Tromsø Study (2015-2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) at the geographical subdivision level. Individual-level SES data and geographical subdivision of Tromsø municipality (36 areas) were obtained from Statistics Norway. Variables from questionnaires and clinical examinations obtained from Tromsø7 were used as mediators (smoking, snuff, alcohol, and physical activity), while the outcome variables were body mass index (BMI), total/high-density lipoprotein (HDL) cholesterol ratio, waist circumference, hypertension, diabetes. Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex. Results: ASES was significantly associated with all outcome variables. CVD risk factor level declined with an increase in ASES. These associations were mediated by differences in smoking habits, alcohol use and physical activity. The associations of ASES with total/HDL cholesterol ratio and waist circumference (women) were moderated by age, and the moderating effects were mediated by smoking and physical activity in both sexes. The largest mediated effects were seen in the associations of ASES with total/HDL cholesterol ratio, with the mediators accounting for 43% of the observed effects. Conclusions: Living in lower SES areas is associated with increased CVD risk due to unhealthy lifestyle behaviors, such as smoking, alcohol use and physical inactivity. These associations were stronger in women and among older participants.

Achievements of primary prevention targets in individuals with high risk of cardiovascular disease: an 8-year follow-up of the Tromsø study.

Aims: To study change over 8 years in cardiovascular risk, achievement of national guideline-based treatment targets of lipids, blood pressure (BP) and smoking in primary prevention of cardiovascular disease (CVD), medication use, and characteristics associated with target achievement among individuals with high CVD risk in a general population. Methods and results: We followed 2524 women and men aged 40-79 years with high risk of CVD attending the population-based Tromsø study in 2007-08 (Tromsø6) to their participation in the next survey in 2015-16 (Tromsø7). We used descriptive statistics and regression models to study change in CVD risk and medication use, and characteristics associated with treatment target achievement. In total, 71.4% reported use of BP- and/or lipid-lowering medication at second screening. Overall, CVD risk decreased during follow-up, with a larger decrease among medication users compared with non-users. Treatment target achievement was 31.0% for total cholesterol <5 mmol/L, 27.3% for LDL cholesterol <3 mmol/L, 43.4% for BP <140/90 (<135/85 if diabetes) mmHg, and 85.4% for non-smoking. A total of 9.8% reached all treatment targets combined. Baseline risk factor levels and current medication use had the strongest associations with treatment target achievement. Conclusion: We found an overall improvement in CVD risk factors among high-risk individuals over 8 years. However, guideline-based treatment target achievement was relatively low for all risk factors except smoking. Medication use was the strongest characteristic associated with achieving treatment targets. This study has demonstrated that primary prevention of CVD continues to remain a major challenge.

Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study.

AIM: To test the association of alcohol consumption with total and cause-specific mortality risk. DESIGN: Prospective observational multi-centre population-based study. SETTING: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. PARTICIPANTS: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). MEASUREMENTS: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. FINDINGS: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7-14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7-20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10-35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. CONCLUSIONS: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.

Treatment target achievement after myocardial infarction and ischaemic stroke: cardiovascular risk factors, medication use, and lifestyle: the Tromsø Study 2015-16.

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.

Association of iron deficiency with incident cardiovascular diseases and mortality in the general population.

AIMS: Although absolute (AID) and functional iron deficiency (FID) are known risk factors for patients with cardiovascular (CV) disease, their relevance for the general population is unknown. The aim was to assess the association between AID/FID with incident CV disease and mortality in the general population. METHODS AND RESULTS: In 12 164 individuals from three European population-based cohorts, AID was defined as ferritin < 100 µg/L or as ferritin < 30 µg/L (severe AID), and FID was defined as ferritin < 100 µg/L or ferritin 100-299 µg/L and transferrin saturation < 20%. The association between iron deficiency and incident coronary heart disease (CHD), CV mortality, and all-cause mortality was evaluated by Cox regression models. Population attributable fraction (PAF) was estimated. Median age was 59 (45-68) years; 45.2% were male. AID, severe AID, and FID were prevalent in 60.0%, 16.4%, and 64.3% of individuals. AID was associated with CHD [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39, P = 0.01], but not with mortality. Severe AID was associated with all-cause mortality (HR 1.28, 95% CI 1.12-1.46, P < 0.01), but not with CV mortality/CHD. FID was associated with CHD (HR 1.24, 95% CI 1.07-1.43, P < 0.01), CV mortality (HR 1.26, 95% CI 1.03-1.54, P = 0.03), and all-cause mortality (HR 1.12, 95% CI 1.01-1.24, P = 0.03). Overall, 5.4% of all deaths, 11.7% of all CV deaths, and 10.7% of CHD were attributable to FID. CONCLUSIONS: In the general population, FID was highly prevalent, was associated with incident CHD, CV death, and all-cause death, and had the highest PAF for these events, whereas AID was only associated with CHD and severe AID only with all-cause mortality. This indicates that FID is a relevant risk factor for CV diseases in the general population.

Long-Term Survival, Causes of Death, and Trends in 5-Year Mortality After Intracerebral Hemorrhage: The Tromsø Study.

BACKGROUND AND PURPOSE: Data on long-term survival after intracerebral hemorrhage (ICH) are scarce. In a population-based nested case-control study, we compared long-term survival and causes of death within 5 years in 30-day survivors of first-ever ICH and controls, assessed the impact of cardiovascular risk factors on 5-year mortality, and analyzed time trend in 5-year mortality in ICH patients over 2 decades. METHODS: We included 219 participants from the population-based Tromsø Study, who after the baseline participation had a first-ever ICH between 1994 to 2013 and 1095 age- and sex-matched participants without ICH. Cumulative survival was presented using the Kaplan-Meier method. Hazard ratios (HRs) for mortality and for the association between cardiovascular risk factors and 5-year mortality in 30-day survivors were estimated by stratified Cox proportional hazards models. Trend in 5-year mortality was assessed by logistic regression. RESULTS: Risk of death during follow-up (median time, 4.8 years) was increased in the ICH group compared with controls (HR, 1.62 [95% CI, 1.27-2.06]). Cardiovascular disease was the leading cause of death, with a higher proportion in ICH patients (22.9% versus 9.0%; P<0.001). Smoking increased the risk of 5-year mortality in cases and controls (HR, 1.59 [95% CI, 1.15-2.19]), whereas serum cholesterol was associated with 5-year mortality in cases only (HR, 1.39 [95% CI, 1.04-1.86]). Use of anticoagulants at ICH onset increased the risk of death (HR, 2.09 [95% CI, 1.09-4.00]). There was no difference according to ICH location (HR, 1.15 [95% CI, 0.56-2.37]). Five-year mortality did not change during the study period (odds ratio per calendar year, 1.01 [95% CI, 0.93-1.09]). CONCLUSIONS: Survival rates were significantly lower in cases than in controls, driven by a 2-fold increased risk of cardiovascular death. Smoking, serum cholesterol, and use of anticoagulant drugs were associated with increased risk of death in ICH patients. Five-year mortality rates in ICH patients remained stable over time.

Age-specific atrial fibrillation incidence, attributable risk factors and risk of stroke and mortality: results from the MORGAM Consortium.

BACKGROUND: The main aim was to examine age-specific risk factor associations with incident atrial fibrillation (AF) and their attributable fraction in a large European cohort. Additionally, we aimed to examine risk of stroke and mortality in relation to new-onset AF across age. METHODS: We used individual-level data (n=66 951, 49.1% men, age range 40-98 years at baseline) from five European cohorts of the MOnica Risk, Genetics, Archiving and Monograph Consortium. The participants were followed for incident AF for up to 10 years and the association with modifiable risk factors from the baseline examinations (body mass index (BMI), hypertension, diabetes, daily smoking, alcohol consumption and history of stroke and myocardial infarction (MI)) was examined. Additionally, the participants were followed up for incident stroke and all-cause mortality after new-onset AF. RESULTS: AF incidence increased from 0.9 per 1000 person-years at baseline age 40-49 years, to 17.7 at baseline age ≥70 years. Multivariable-adjusted Cox models showed that higher BMI, hypertension, high alcohol consumption and a history of stroke or MI were associated with increased risk of AF across age groups (p<0.05). Between 30% and 40% of the AF risk could be attributed to BMI, hypertension and a history of stroke or MI. New-onset AF was associated with a twofold increase in risk of stroke and death at ages≥70 years (p≤0.001). CONCLUSION: In this large European cohort aged 40 years and above, risk of AF was largely attributed to BMI, high alcohol consumption and a history MI or stroke from middle age. Thus, preventive measures for AF should target risk factors such as obesity and hypertension from early age and continue throughout life.

Is the ongoing obesity epidemic partly explained by concurrent decline in cigarette smoking? Insights from a longitudinal population study. The Tromsø Study 1994-2016.

The increase of obesity coincides with a substantial decrease in cigarette smoking. We assessed post-cessation weight change and its contribution to the obesity epidemic in a general population in Norway. A total of 14,453 participants (52.6% women), aged 25-54 years in 1994, who attended at least two of four surveys in the Tromsø Study between 1994 and 2016, were included in the analysis. Hereof 77% participated in both the first and the last survey. Temporal trends in mean body mass index (BMI), prevalence of obesity (BMI ≥ 30 kg/m2) and daily smoking were estimated with generalized estimation equations. We assessed BMI change by smoking status (ex-smoker, quitter, never smoker, daily smoker), and also under a scenario where none quit smoking. In total, the prevalence of daily smoking was reduced over the 21 years between Tromsø 4 (1994-1995) and Tromsø 7 (2015-2016) by 22 percentage points. Prevalence of obesity increased from 5 - 12% in 1994-1995 to 21-26% in 2015-2016, where obesity in the youngest (age 25-44 in 1994) increased more than in the oldest (p < 0.0001). Those who quit smoking had a larger BMI gain compared to the other three smoking subgroups over the 21 years (p < 0.0001). The scenario where none quit smoking would imply a 13% reduction in BMI gain in the population, though substantial age-related differences were noted. We conclude that smoking cessation contributed to the increase in obesity in the population, but was probably not the most important factor. Public health interventions should continue to target smoking cessation, and also target obesity prevention.

Hypothetical interventions and risk of myocardial infarction in a general population: application of the parametric g-formula in a longitudinal cohort study-the Tromsø Study.

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.

Does Estimated Pulse Wave Velocity Add Prognostic Information?: MORGAM Prospective Cohort Project.

The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.

Secular and longitudinal trends in cardiovascular risk in a general population using a national risk model: The Tromsø Study.

BACKGROUND: Primary prevention guidelines promote the use of risk assessment tools to estimate total cardiovascular risk. We aimed to study trends in cardiovascular risk and contribution of single risk factors, using the newly developed NORRISK 2 risk score, which estimates 10-year risk of fatal and non-fatal cardiovascular events. DESIGN: Prospective population-based study. METHODS: We included women and men aged 45-74 years attending the sixth and seventh survey of the Tromsø Study (Tromsø 6, 2007-2008, n = 7284 and Tromsø 7, 2015-2016, n = 14,858) to study secular trends in NORRISK 2 score. To study longitudinal trends, we followed participants born 1941-1962 attending both surveys (n = 4534). We calculated NORRISK 2 score and used linear regression models to study the relative contribution (%R2) of each single risk factor to the total score. RESULTS: Mean NORRISK 2 score decreased and distribution in risk categories moved from higher to lower risk in both sexes and all age-groups between the first and second surveys (p < 0.001). In birth cohorts, when age was set to baseline in NORRISK 2 calculations, risk score decreased during follow-up. Main contributors to NORRISK 2 were systolic blood pressure, smoking and total cholesterol, with some sex, age and birth cohort differences. CONCLUSION: We found significant favourable secular and longitudinal trends in total cardiovascular risk and single risk factors during the last decade. Change in systolic blood pressure, smoking and cholesterol were the main contributors to risk score change; however, the impact of single risk factors on the total score differed by sex, age and birth cohort.

The association between red cell distribution width and venous thromboembolism is not explained by myocardial infarction, stroke, or cancer.

BACKGROUND: Red cell distribution width (RDW) is a risk marker of venous thromboembolism (VTE), myocardial infarction (MI), stroke, and cancer. Due to interrelations between these diseases, the association between RDW and VTE may be explained by MI, stroke, or cancer. OBJECTIVE: To investigate whether the effect of RDW on VTE could be explained by intermediate development of MI, stroke, or cancer. METHODS: RDW was measured in 24 363 participants of the Tromsø Study in 1994-1995. Incident VTE, MI, stroke, and cancer were registered until December 31, 2010. Conventional and cause-specific Cox-regression models were used to estimate hazard ratios (HR) for VTE with 95% confidence intervals (CI) across categories of RDW. RESULTS: There were 502 first VTEs during a median follow-up of 16 years. In conventional Cox regression analysis, RDW in the highest quartile was associated with a 71% (HR 1.71, 95% CI 1.09-2.67) and 27% (HR 1.27, 95% CI 0.88-1.85) higher risk of VTE in men and women, respectively, compared to subjects in the lowest quartiles. The risk of VTE among subjects with RDW in the highest quartile was similar for men and women of postmenopausal age. In cause-specific analysis, where each individual contributed with person-time until the first occurring event only, the risk estimates were similar to those of the conventional Cox-regression analysis. CONCLUSION: Our findings suggest that the association between RDW and future risk of VTE is not explained by intermediate development of MI, stroke, or cancer.

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies. FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

Association of occasional smoking with total mortality in the population-based Tromsø study, 2001-2015.

OBJECTIVES: There is a shift in the smoking population from daily smokers to light or occasional smokers. The knowledge about possible adverse health effects of this new smoking pattern is limited. We investigated smoking habits with focus on occasional smoking in relation to total mortality in a follow-up study of a Norwegian general population. SETTING: A population study in Tromsø, Norway. METHODS: We collected smoking habits and relevant risk factors in 4020 women and 3033 men aged 30-89 years in the Tromsø Study in 2001. The subjects were followed up regarding total mortality through June 2015. RESULTS: Among the participants, there were 7% occasional smokers. Occasional smokers were younger, more educated and used alcohol more frequently than other participants. A total of 766 women and 882 men died during the follow-up. After the adjustment for confounders, we found that occasional smoking significantly increased mortality by 38% (95% CI 8% to 76%) compared with never smokers. We report a dose-response relationship in the hazards of smoking (daily, occasional, former and never smoking). CONCLUSIONS: Occasional smoking is not a safe smoking alternative. There is a need for information to the general public and health workers about the health hazards of occasional smoking. More work should be done to motivate this often well-educated group to quit smoking completely.

Data on gender contrasts in the risk of incident myocardial infarction by age. The Tromsø Study 1979-2012.

The data presented in this article relate to the research article entitled "Risk of incident myocardial infarction by gender: Interactions with serum lipids, blood pressure and smoking. The Tromsø Study 1979-2012" (Albrektsen et al., 2017) [1]. Data quantify the gender differences in the risk of myocardial infarction (MI) in terms of incidence rate ratios (IRR), in subgroups defined by serum lipids, blood pressure and smoking among persons aged 35-54 years, 55-74 years and 75-94 years, respectively. Data also describe the age- and gender-specific linear associations with the coronary heart disease (CHD) risk factors. IRRs for combined categories of age, gender and a CHD risk factor, with each category compared to the same reference group, are also shown. IRRs were calculated as estimates of relative risk in Poisson regression analyses of person-years at risk. Among 33,859 individuals at risk, a total of 622, 1308 and 816 were diagnosed with MI at ages 35-54, 55-74 and 75-94 years, respectively.

Risk of incident myocardial infarction by gender: Interactions with serum lipids, blood pressure and smoking. The Tromsø Study 1979-2012.

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.