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Objectives ‒ Previous studies have suggested that experimental pain sensitivity is associated with cognitive function. The aim of this study is to assess this relationship in a large population-based sample. Methods ‒ We included 5,753 participants (aged 40–84 years) from the seventh wave of the population-based Tromsø Study who had been examined with cognitive tests and experimental pain assessments, and for whom information on covariates were available. Cox regression models were fitted using standardized scores on cognitive tests (12- word immediate recall test, digit symbol coding test, and Mini-Mental State Examination [MMS-E]) as the independent variable and cold pressor or cuff pressure pain tolerance as the dependent variables. Statistical adjustment was made for putative confounders, namely, age, sex, education, smoking, exercise, systolic blood pressure, body mass index, symptoms indicating anxiety or depression, analgesic use, and chronic pain. Results ‒ In multivariate analysis, cold pressor tolerance time was significantly associated with test scores on the 12- word immediate recall test (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90–0.97, p < 0.001), the digit symbol coding test (HR 0.94, 95% CI 0.89–0.98, p = 0.004), and the MMS-E (HR 0.93, 95% CI 0.90–0.96 p < 0.001). Tolerance to cuff pressure algometry was significantly associated with 12-word immediate recall (HR 0.94–0.97, p < 0.001) and Digit Symbol Coding test scores (HR 0.93, 95% CI 0.89–0.96, p < 0.001) while there was no significant association with Mini Mental State Examination test score (HR 0.98, 95% CI 0.95–1.00, p = 0.082). Conclusion ‒ Lower pain tolerance was associated with poorer performance on cognitive tests. [ABSTRACT FROM AUTHOR]

Aim: To assess whether stroke diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for the Tromsø Study, a population-based epidemiological study. Method: Using the Tromsø Study Cardiovascular Disease Register for 2013–2014 as the gold standard, we calculated correctness (defined as positive predictive value, PPV) and completeness (defined as sensitivity) of stroke cases in four different data subsets derived from the Norwegian Patient Register and the Norwegian Stroke Register. We calculated the sensitivity and PPV with 95% confidence intervals (CIs) assuming a normal approximation of the binomial distribution. Results: In the Norwegian Stroke Register we found a sensitivity of 79.8% (95% CI 74.2–85.4) and a PPV of 97.5% (95% CI 95.1–99.9). In the Norwegian Patient Register the sensitivity was 86.4% (95% CI 81.6–91.1) and the PPV was 84.2% (95% CI 79.2–89.2). The overall highest levels were found in a subset based on a linkage between the Norwegian Stroke Register and the Norwegian Patient Register, with a sensitivity of 88.9% (95% CI 84.5–93.3), and a PPV of 89.3% (95% CI 85.0–93.6). Conclusions: Data from the Norwegian Patient Register and from the linked data set between the Norwegian Patient Register and the Norwegian Stroke Register had acceptable levels of correctness and completeness to be considered as endpoint sources for the Tromsø Study Cardiovascular Disease Register. The benefits of using data from national registers as endpoints in epidemiological studies must be weighed against the impact of potentially decreased data quality. [ABSTRACT FROM AUTHOR]

Background: Stroke lesions might alter pain processing and modulation by affecting the widely distributed network of brain regions involved. We aimed to compare pain tolerance in stroke survivors and stroke‐free persons in the general population, with and without chronic pain. Methods: We included all participants of the sixth and seventh wave of the population‐based Tromsø Study who had been tested with the cold pressor test (hand in cold water bath, 3°C, maximum time 106 s in the sixth wave and 120 s in the seventh) and who had information on previous stroke status and covariates. Data on stroke status were obtained from the Tromsø Study Cardiovascular Disease Register and the Norwegian Stroke Register. Cox regression models were fitted using stroke prior to study attendance as the independent variable, cold pressor endurance time as time variable and hand withdrawal from cold water as event. Statistical adjustments were made for age, sex, diabetes, hypertension, hyperlipidaemia, body mass index and smoking. Results: In total 21,837 participants were included, 311 of them with previous stroke. Stroke was associated with decreased cold pain tolerance time, with 28% increased hazard of hand withdrawal (hazard ratio [HR] 1.28, 95% CI 1.10–1.50). The effect was similar in participants with (HR 1.28, 95% CI 0.99–1.66) and without chronic pain (HR 1.29, 95% CI 1.04–1.59). Conclusions: Stroke survivors, with and without chronic pain, had lower cold pressor pain tolerance, with possible clinical implications for pain in this group. Significance: We found lower pain tolerance in participants with previous stroke compared to stroke‐free participants of a large, population‐based study. The association was present both in those with and without chronic pain. The results may warrant increased awareness by health professionals towards pain experienced by stroke patients in response to injuries, diseases and procedures. [ABSTRACT FROM AUTHOR]

Aims To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables. Methods and results In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82–2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13–1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10–1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02–1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index. Conclusion Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively. [ABSTRACT FROM AUTHOR]

Objectives. Urinary albumin excretion is a risk marker for cardiovascular disease (CVD). Studies suggest that urinary orosomucoid may be a more sensitive marker of general endothelial dysfunction than albuminuria. The aim of this population-based cross-sectional study was to examine the associations between urinary orosomucoid to creatinine ratio (UOCR), urinary albumin to creatinine ratio (UACR) and subclinical CVD. Design. From the Tromsø Study (2007/2008), we included all men and women who had measurements of urinary orosomucoid (n = 7181). Among these, 6963 were examined with ultrasound of the right carotid artery and 2245 with echocardiography. We assessed the associations between urinary markers and subclinical CVD measured as intima media thickness of the carotid artery, presence and area of carotid plaque and diastolic dysfunction (DD). UOCR and UACR were dichotomized as upper quartile versus the three lowest. Results. High UOCR, adjusted for UACR, age, cardiovascular risk factors and kidney function, was associated with presence of DD in men (OR: 3.18, 95% CI [1.27, 7.95], p =.013), and presence of plaque (OR: 1.20, 95% CI [1.01, 1.44], p =.038) and intima media thickness in women (OR: 1.34, 95% CI [1.09, 1.65], p =.005). Analyses showed no significant interaction between sex and UOCR for any endpoints. UACR was not significantly associated with DD, but the associations with intima media thickness and plaque were of magnitudes comparable to those observed for UOCR. Conclusions. UOCR was positively associated with subclinical CVD. We need prospective studies to confirm whether UOCR is a clinically useful biomarker and to study possible sex differences. [ABSTRACT FROM AUTHOR]

Background: Management of incidental unruptured intracranial aneurysms (UIAs) remains challenging and depends on their risk of rupture, estimated from the assumed prevalence of aneurysms and the incidence of aneurysmal subarachnoid haemorrhage. Reported prevalence varies, and consistent criteria for definition of UIAs are lacking. We aimed to study the prevalence of UIAs in a general population according to different definitions of aneurysm.Methods: Cross-sectional population-based study using 3-dimensional time-of-flight 3 Tesla MR angiography to identify size, type and location of UIAs in 1862 adults aged 40-84 years. Size was measured as the maximal distance between any two points in the aneurysm sac. Prevalence was estimated for different diameter cutoffs (≥1, 2 and 3 mm) with and without inclusion of extradural aneurysms.Results: The overall prevalence of intradural saccular aneurysms ≥2 mm was 6.6% (95% CI 5.4% to 7.6%), 7.5% (95% CI 5.9% to 9.2%) in women and 5.5% (95% CI 4.1% to 7.2%) in men. Depending on the definition of an aneurysm, the overall prevalence ranged from 3.8% (95% CI 3.0% to 4.8%) for intradural aneurysms ≥3 mm to 8.3% (95% CI 7.1% to 9.7%) when both intradural and extradural aneurysms ≥1 mm were included.Conclusion: Prevalence in this study was higher than previously observed in other Western populations and was substantially influenced by definitions according to size and extradural or intradural location. The high prevalence of UIAs sized <5 mm may suggest lower rupture risk than previously estimated. Consensus on more robust and consistent radiological definitions of UIAs is warranted. [ABSTRACT FROM AUTHOR]

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings.Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding.Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting.Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Trial Registration: ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 . [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Patients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT. Methods/design: TWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase (n=300) versus standard care (n=300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0-6) at three months. Discussion: TWISTaims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT. Trial registration: ClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80 [ABSTRACT FROM AUTHOR]

Purpose: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study. Patients and Methods: Using the Tromsø Study Cardiovascular Disease Register for 2013– 2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test. Results: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8– 99.2) and a sensitivity of 88.2% (95% CI 82.0– 92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6– 98.8) and the sensitivity was 85.6% (95% CI 79.0– 90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1– 98.9) and a sensitivity of 91.5% (95% CI 85.9– 95.4). Conclusion: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromsø Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area. [ABSTRACT FROM AUTHOR]

Aims  There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts. Methods and results  In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11–1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF. Conclusions  In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention. [ABSTRACT FROM AUTHOR]

Objectives Large differences exist in the burden of cardiovascular disease (CVD) between Russia and Western European countries including Norway. Obesity prevalence may contribute to the differences. We investigated whether difference in the level of adiposity, assessed using body mass index and waist-to-hip ratio(WHR), could explain intercountry differences in the burden of carotid plaque, a measure of atherosclerosis, in the populations. Design Cross-sectional analysis. Logistic and linear regression models were used. Setting We used population-based cross-sectional Know Your Heart (KYH) study in Russia and the Tromsø 7 study (Tromsø 7) in Norway. Participants 3262 and 1800 men and women aged 40–69 years in KYH and Tromsø 7, respectively. Primary and secondary outcome The presence of carotid plaques and plaque score assessed using ultrasound. Results The presence of carotid plaques and plaque score were higher in KYH than Tromsø 7 regardless of age group and sex. A positive association between carotid plaque burden and adiposity was found (OR of having at least one plaque per SD in WHR 1.18 (95% CI 1.06 to 1.31) for men; 1.15 (1.06 to 1.25) for women)) adjusted for age, smoking and education in a pooled analysis of the two studies. There was little evidence of the interaction between study and adiposity. These effects did not differ between the two studies. However, neither adiposity nor CVD risk factors (smoking, systolic blood pressure, cholesterol, glycosylated haemoglobin) explained the higher carotid plaque burden in KYH compared with Tromsø 7. Conclusion Adiposity, especially abdominal adiposity, is a risk factor for carotid plaque in Russia and Norway, although neither adiposity nor established CVD risk factors explained the higher plaque burden in Russia. To reduce the CVD burden in Russia, beyond prevention and treatment of adiposity, further research is required to understand why Russia has a high burden of atherosclerosis. [ABSTRACT FROM AUTHOR]

Aims To explore sex-specific associations between long-term individual blood pressure (BP) patterns and risk of incident atrial fibrillation (AF) in the general population. Methods and results Blood pressure was measured in 8376 women and 7670 men who attended at least two of the three population-based Tromsø Study surveys conducted in 1986–87, 1994–95, and 2001. Participants were followed for incident AF throughout 2013. Latent mixed modelling was used to identify long-term trajectories of systolic BP and hypertension. Cox regression was used to estimate associations between the identified trajectories and incident AF. Elevated systolic BP throughout the exposure period (1986–2001) independently and differentially increased risk of AF in women and men. In women, having elevated systolic BP trajectories doubled AF risk compared to having persistently low levels, irrespective of whether systolic BP increased, decreased, or was persistently high over time, with hazard ratios of 1.88 (95% confidence interval 1.37–2.58), 2.32 (1.61–3.35), and 1.94 (1.28–2.94), respectively. In men, those with elevated systolic BP that continued to increase over time had a 50% increased AF risk: 1.51 (1.09–2.10). When compared to those persistently normotensive, women developing hypertension during the exposure period, and women and men with hypertension throughout the exposure period had 1.40 (1.06–1.86), 2.75 (1.99–3.80), and 1.36 (1.10–1.68) times increased risk of AF, respectively. Conclusion Long-term BP and hypertension trajectories were associated with increased incidence of AF in both women and men, but the associations were stronger in women. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Aims: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality.Methods and Results: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001).Conclusion: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes. [ABSTRACT FROM AUTHOR]

Background: Few reports are available on the contribution of general and abdominal obesity to the progression of carotid atherosclerosis in late adulthood. This study investigated the impact of four simple anthropometric measures of general and abdominal obesity on the progression of carotid atherosclerosis and the extent to which the association between adiposity and the progression of plaque burden is mediated by cardiometabolic markers.Methods: Four thousand three hundred forty-five adults (median age 60) from the population-based Tromsø Study were followed over 7 years from the first carotid ultrasound screening to the next. The progression of carotid atherosclerosis was measured in three ways: incidence of plaques in previously plaque-free participants; change in the number of plaques; and total plaque area (TPA). We used generalised linear models to investigate the association between each adiposity measure - body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) - and each outcome. Models were adjusted for potential confounders (age, sex, smoking, education, physical activity). The pathways through which any associations observed might operate were investigated by further adjusting for cardiometabolic mediators (systolic blood pressure, cholesterol, and HbA1c).Results: There was little evidence that adiposity was related to the formation of new plaques during follow-up. However, abdominal adiposity was associated with TPA progression. WHtR showed the largest effect size (mean change in TPA per one standard deviation (SD) increase in WHtR of 0.665 mm2, 95% confidence interval 0.198, 1.133) while BMI showed the smallest. Effect sizes were substantially reduced after the adjustment for potential mediators.Conclusions: Abdominal obesity indirectly measured with WC seems more strongly associated with the progression of TPA than general obesity. These associations appear to be largely mediated by known cardiometabolic markers. [ABSTRACT FROM AUTHOR]

The article reports about how carotid intima–media thickness (cIMT) together with the carotid plaque are accurate predictors of cardiovascular (CV). Topics include increased cIMT being considered as a manifestation of subclinical atherosclerosis and has been comprised in the list of organ damage conditions in the European Hypertension Guideline; and cIMT being biologically and genetically distinct from plaque burden and failure to distinguish between two different approaches to measuring cIMT.

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. [ABSTRACT FROM AUTHOR]

The effects of interventions on multiple lifestyle and metabolic risk factors, initiated in midlife or later in a healthy population, on the long-term risk of first-ever stroke is not known. A particular methodological challenge in observational studies is to estimate the unbiased effect of a time-varying exposure in presence of time-varying confounders, if those confounders are affected by prior exposure. In such cases, the parametric g-formula can be applied to estimate an unbiased effect. We applied the parametric g-formula to estimate the 18-years (1994-2012) cumulative stroke risk under different scenarios of hypothetical interventions on levels of blood pressure, cholesterol, weight, physical activity, smoking and alcohol intake; and compared these to the observed scenario, to calculate the population risk ratios and risk differences. Among 14,796 eligible participants in the prospective, population-based Tromsø study (baseline mean age 46.1 years, 51% women), the observed 18-years stroke risk was 5.9%. A feasible joint hypothetical intervention on six lifestyle and metabolic risk factors would reduce the 18-year stroke risk by 32% (95% confidence interval 16, 44). A combination of more intensive interventions reduced the estimated 18-years stroke risk by 64% (95% confidence interval 40, 80). Blood pressure reduction and quitting smoking significantly reduced the risk when applied separately. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives Elevated blood cholesterol is a modifiable risk factor for cardiovascular disease. Cholesterol level surveillance is necessary to study population disease burden, consider priorities for prevention and intervention and understand the effect of diet, lifestyle and treatment. Previous studies show a cholesterol decline in recent decades but lack data to follow individuals born in different decades throughout life. Methods We investigated changes in age-specific and birth cohort-specific total cholesterol (TC) levels in 43 710 women and men born in 1905-1977 (aged 20-95 years at screening) in the population-based Tromsø Study. Fifty-nine per cent of the participants had more than one and up to six repeated TC measurements during 1979-2016. Linear mixed models were used to test for time trends. Results Mean TC decreased during 1979-2016 in both women and men and in all age groups. The decrease in TC in age group 40-49 years was 1.2 mmol/L in women and 1.0 mmol/L in men. Both the 80th and the 20th percentile of the population TC distribution decreased in both sexes and all age groups. Longitudinal analysis showed that TC increased with age to a peak around middle age followed by a decrease. At any given age, TC significantly decreased with increase in year born. Lipid-lowering drug use was rare in 1994, increased thereafter, but was low (<3% in women and <5% in men) among those younger than 50 years in all surveys. Between 1994 and 2016, lipid-lowering drug treatment in individuals 50 years and older explained 21% and 28% of the decrease in TC levels in women and men, respectively. Conclusions We found a substantial decrease in mean TC levels in the general population between 1979 and 2016 in all age groups. In birth cohorts, TC increased with age to a peak around middle age followed by a decrease. [ABSTRACT FROM AUTHOR]

Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population.~Aims~Unassigned~Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption.~Methods~Unassigned~The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (<5 g per day) had significantly lower common CIMT values than those consuming >10 g per day, after adjusting for a range of confounding factors.~Results~Unassigned~In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT.~Conclusion~Unassigned [ABSTRACT FROM AUTHOR]

Purpose To provide sex-stratified normative data on retinal thickness and study the relationship with sex, age and refractive status. Methods Population-based study including 2617 women and 1891 men, aged 38-87 (mean 61 ± 8) years, without diabetes, glaucoma and retinal diseases, and spherical equivalent refraction ( SER) within ±6 dioptres. Retinal thickness was measured with optical coherence tomography (spectral domain Cirrus HD- OCT). Results Women had thinner retina than men. Retinal thickness was significantly associated with refraction, where mean change in retinal thickness per 1 D increase in SER was −1.3 (0.2) μm in the fovea, 0.7 (0.1) μm in the pericentral ring and 1.4 (0.1) μm in the peripheral ring. In the fovea, there was a non-monotonic curved relationship between retinal thickness and age in both sexes with a maximum at about 60 years (p < 0.001). In the pericentral ring, the mean reduction in retinal thickness per 10-year increase was 2.7 (0.3) μm in women and 4.0 (0.4) μm in men and corresponding results in the peripheral ring were 2.3 (0.3) μm in women and 2.6 (0.4) μm in men. In both regions, there was evidence for a nonlinear pattern with an increased rate of change with higher age. There was a significant interaction between sex and age for retinal thickness of the pericentral ring (p = 0.041). Conclusion Women had thinner retina than men, and thickness varied with refractive status. Retinal thickness was associated with age in all macular regions, and the rate of change in retinal thickness varied at different ages. [ABSTRACT FROM AUTHOR]

Background: The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation. Methods: Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group. Results: Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women. Conclusion: Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality. Methods: In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488. Findings: We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00–1.29), 1.33 (1.16–1.51), and 1.67 (1.44–1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L. Interpretation: In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths. [ABSTRACT FROM AUTHOR]

Background: Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. Methods: We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounderswere used to study the association between OPG and eGFR. Analyseswere stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. Results: In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73m2) eGFR increased by 0.35 mL/min/1.73m2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73m2), eGFR decreased by 1.54 (95% CI - 2.06 to - 1.01) per 1 SD increase in serum OPG. Conclusions: OPGwas associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]