Background Cardiac troponins represent a sensitive index of subclinical myocardial injury and are associated with increased risk of cardiovascular events in the general population. Despite positive associations with cardiovascular risk of both cardiac troponins and cigarette smoking, concentrations of cardiac troponin I measured by high‐sensitivity assays (hs‐cTnI) are paradoxically lower in current smokers than in never‐smokers. The impact of smoking intensity and time from smoking cessation on hs‐cTnI remains unknown. Methods and Results hs‐cTnI concentrations were measured in 32028 subjects free from cardiovascular disease enrolled in the prospective, population‐based HUNT (Trøndelag Health Study). Tobacco habits were self‐reported and classified as never (n=14 559), former (n=14 248), and current (n=3221) smokers. Current smokers exhibited significantly lower concentrations of hs‐cTnI than never‐smokers ( P <0.001). In adjusted models, both current smoking (−17.3%; 95% CI, −20.6 to −13.9%) and former smoking (−6.6%; 95% CI, −8.7 to −4.5%) were associated with significantly lower hs‐cTnI concentrations. Among former smokers, higher smoking burden (>10 pack‐years) were associated with lower concentrations of hs‐cTnI. Time since smoking cessation was associated with increasing concentrations of hs‐cTnI in a dose‐dependent manner ( P for trend<0.001), and subjects who quit smoking >30 years ago had concentrations of hs‐cTnI comparable with those of never‐smokers. Conclusions In the general population, both current and former cigarette smoking is associated with lower concentrations of hs‐cTnI. In former smokers, there was a dose‐response relationship between pack‐years of smoking, and hs‐cTnI. Time since smoking cessation was associated with increasing concentrations of hs‐cTnI, indicating a continuum of hs‐cTnI from current smoker to never‐smokers.
To evaluate the association between self-reported alcohol consumption and phosphatidylethanol (PEth) concentrations in blood in a large general population study, and discuss optimal cut-off PEth concentrations for defined levels of alcohol consumption.Population based, longitudinal cohort study including 24,574 adults from The Trøndelag Health Study 4 (HUNT4) conducted in Trøndelag County, Norway. Data included PEth concentration, self-reported alcohol consumption and CAGE score.PEth levels in whole blood increased with the number of alcohol units consumed, the frequency of alcohol consumption, the frequency of binge drinking and the CAGE score (lifetime, i.e. 'have you ever'). The cut-off concentrations with highest combined sensitivity and specificity were 0.057 μmol/l (40 ng/ml) for identification of those consuming >1 alcohol unit per day (sensitivity 86%, specificity 76%), 0.087 μmol/l (61 ng/ml) for consuming >2 units per day (sensitivity 87%, specificity 81%) and 0.122 μmol/l (86 ng/ml) for consuming >3 alcohol units per day (sensitivity 80%, specificity 86%). By defining a CAGE score ≥ 2 as potentially harmful consumption, a cut-off of 0.100 μmol/l (70 ng/ml) identified 52% of all those subjects.Cut-off limits of PEth concentrations should take into account the indication for sampling. Using cut-offs for the PEth concentrations of about 0.05 μmol/l (35 ng/ml) and 0.08 μmol/l (56 ng/ml) would identify about 90% of the subjects consuming more than 1 and 2 alcohol units per day, respectively. Concentrations above these cut-offs should lead to a more detailed interview related to alcohol use.
We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.
Summary Cerebrovascular accident (stroke) is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, which could be due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ancestries to study the genetic contributions underlying ischemic stroke (60,176 cases, 1,310,725 controls) as part of the Global Biobank Meta-analysis Initiative (GBMI). Two novel loci associated ischemic stroke with plausible candidate genes, FGF5 and CENPQ/MUT , were identified after replication in four additional datasets. One locus showed significant ancestry heterogeneity ( PDE3A ) and two loci showed significant sex-heterogeneity ( SH3PXD2A and ALDH2 ). The ALDH2 locus had a male-specific association for stroke in GBMI (P-value males = 1.67e-24, P-value females = 0.126). To test whether we would see a difference in the predictive power of sex-specific polygenic risk scores (PRSs), we compared the C-indexes for sex-specific and sex-combined PRSs in HUNT dataset. A sex-combined PRS was more successful at predicting stroke cases than a sex-specific PRS, most likely due to more stable effect estimates from the sex-combined summary-statistics. These approaches can be applied to further unravel the genetic underpinnings of stroke and other complex diseases.
OBJECTIVE To assess the association between use of sodium–glucose cotransporter 2 (SGLT2) inhibitors and the risk of new-onset atrial fibrillation (AF) in routine clinical practice. RESEARCH DESIGN AND METHODS We used nationwide registers in Denmark, Norway, and Sweden from 2013 to 2018 in order to include patients without a history of AF who were newly prescribed an SGLT2 inhibitor or an active comparator (glucagon-like peptide 1 [GLP-1] receptor agonist). We performed a cohort study to assess new-onset AF in intention-to-treat analyses using Cox regression, adjusted for baseline covariates with propensity score weighting. RESULTS We identified 79,343 new users of SGLT2 inhibitors (59.2% dapagliflozin, 40.0% empagliflozin, 0.8% canagliflozin, <0.1% ertugliflozin) and 57,613 new users of GLP-1 receptor agonists. Mean age of the study cohort was 61 years and 60% were men. The adjusted incidence rate of new-onset AF was 8.6 per 1,000 person-years for new users of SGLT2 inhibitors compared with 10.0 per 1,000 person-years for new users of GLP-1 receptor agonists. The adjusted hazard ratio (aHR) was 0.89 (95% CI 0.81–0.96), and the rate difference was 1.4 fewer events per 1,000 person-years (95% CI 0.6–2.1). Using an as-treated exposure definition, the aHR for new-onset AF was 0.87 (95% CI 0.76–0.99). No statistically significant heterogeneity of the aHRs was observed between subgroups of patients with and without a history of heart failure or major cardiovascular disease. CONCLUSIONS In this cohort study using nationwide data from three countries, use of SGLT2 inhibitors, compared with GLP-1 receptor agonists, was associated with a modestly reduced risk of new-onset AF.
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