Jonas Andersson

Objectives: To examine the 36-year trends in tobacco use in northern Sweden. Design and outcome measure: Cross-sectional analysis of the eight population-based surveys that constitute the northern Sweden MONICA study (1986, 1990, 1994, 1999, 2004, 2009, 2014 and 2022). Cigarette smoking and snus use were self-reported via questionnaires, and age-adjusted percentages of cigarette smoking (including occasional use) and snus use were calculated via logit models. Setting: General population of Norrbotten and Västerbotten (the two northernmost counties of Sweden). Participants: 6678 women and 6320 men, aged 25 to 74 years, were included for analysis. A total of 191 participants were excluded due to missing data on either cigarette smoking or snus use. Results: Cigarette smoking decreased on a survey-to-survey basis, reaching a minimum in 2022 of 4.9% among men and 9.7% among women, corresponding to a percentage point change of 26.3 and 20.8, respectively, compared with 1986 (p _within-group within-group within-group between-group <0.01). Conclusions: A substantial decline in cigarette smoking has occurred over time in northern Sweden, particularly among men and more notably in Västerbotten. In contrast, snus use has become increasingly common in both sexes and in both counties.

Background: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self‐reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. Methods and Results: We used data from the population‐based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self‐report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self‐report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self‐report tool (n=14 variables) and the clinical tool (n=23 variables) showed high‐to‐excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P <0.001). The tools showed a larger net benefit in clinical decision‐making at relevant threshold probabilities. The self‐report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest‐risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. Conclusions: We have developed a self‐report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self‐report tool may serve as prescreening tool toward a cost‐effective computed tomography‐based screening program for high‐risk individuals.

Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case–control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10⁻⁷). GPR15 expression correlated with intima-media thickness (β = 0.8498, p = 0.111), C-reactive protein (β = 0.2238, p = 0.0052), ejection fraction (β = −0.9991, p = 0.0281) and smoking (β = 0.7259, p = 2.79 × 10⁻¹⁰). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10⁻⁵) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10⁻⁶/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15^gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.

Tobacco consumption is a renal risk factor, but the effects on the estimated glomerular filtration rate (eGFR) remain unclear. We aimed to evaluate the possible impact of using tobacco products (smoking and snus) on eGFR based on creatinine or cystatin C. We used a first cohort with 949 participants and a second cohort with 995 participants; none had pre-existing renal disease. All subjects donated a blood sample and completed a questionnaire, including questions about tobacco use. To assess the effect on eGFR, hierarchical multiple linear regression models were used. Active smoking associated independently with a higher eGFR_creatinine in all subjects (p < 0.001; β = 0.11). Further analyses stratified for sex, showed similar findings for men (p < 0.001; β = 0.14) and for women (p = 0.026; β = 0.10). eGFR_{cystatin C} was significantly associated with active smoking in all subjects (p = 0.040; β = −0.05), but no association was seen after stratification for sex. Snus did not associate with eGFR. In conclusion, smoking associated significantly with a higher eGFR_creatinine. The mechanism may be renal hyperfiltration of smaller molecules such as creatinine. This is probably caused by substances from smoked tobacco other than nicotine, as no effect was seen for snus.

Impaired renal function is associated both with the development of cardiovascular disease and its prognosis. A new syndrome called ′Shrunken Pore Syndrome′ has been suggested, as the estimated glomerular filtration rate for cystatin C (eGFR_{cystatin C}) is affected earlier due to differences in molecular size compared to eGFR_creatinine. The aim was to investigate if a lower eGFR_{cystatin C}/eGFR_creatinine ratio in a prospective setting increases the risk of later developing a first-ever myocardial infarction (MI) independently of other cardiovascular risk factors. We used a nested case-referent study design within the Northern Sweden Health and Disease Study, and 545 subjects (29.0% women) were identified who prospectively developed a first-ever MI, and their 1054 matched referents. For women, but not for men, one standard deviation (SD) increase of ln z-scores of eGFR_{cystatin C}/eGFR_creatinine ratio was associated with a lower risk of a future MI: odds ratio [95% confidence interval] 0.58 [0.34–0.99], adjusted for apolipoprotein B/A1 ratio, CRP, homocysteine, systolic blood pressure, body mass index, and diabetes. Furthermore, a high eGFR_creatinine associated independently with an increased risk of future MI in men only: OR 1.25 [1.05–1.48]. Thus, for women, a lower eGFR_{cystatin C}/eGFR_creatinine ratio is associated with a higher risk of having a future first-ever MI, and it may be a valuable, easily implemented biomarker for risk of cardiovascular disease.

Background: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). Methods: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. Results: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06–1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09–1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89–0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86–0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88–0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non–high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non–high-density lipoprotein cholesterol. Conclusions: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non–high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.