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IMPORTANCE: Risk stratification strategies in primary prevention of coronary events lack precision.

OBJECTIVE: To determine whether prediction of first coronary events is improved by adding information on coronary atherosclerosis from coronary computed tomography angiography (CCTA) to a model using the pooled cohort equation (PCE) risk score tool and the coronary artery calcification score (CACS).

DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study including individuals aged 50 to 64 years randomly recruited from the general population and examined at 6 university hospitals in Sweden from 2013 to 2018, with a median follow-up of 7.8 years. A sample of 30 154 individuals underwent cardiopulmonary imaging, physical examinations, routine laboratory tests, questionnaires, and/or functional tests. This study included 24 791 individuals without previous cardiovascular disease for whom high-quality CCTA images were available. Events were followed up via registers until September 2024.

EXPOSURES: The information used from the CCTA images was the extent of coronary atherosclerosis (segment involvement score), presence of noncalcified atherosclerosis, and presence of coronary obstructive disease (stenosis ≥50%).

MAIN OUTCOMES AND MEASURES: The outcome was a composite of first occurrence of nonfatal myocardial infarction or death from coronary heart disease.

RESULTS: During follow-up, 304 coronary events occurred. Segment involvement scores of 3 to 4 and greater than 4 and presence of noncalcified atherosclerosis were associated with hazard ratios of 2.71 (95% CI, 1.34-5.44), 5.27 (95% CI, 2.50-11.07), and 1.66 (95% CI, 1.23-2.22), respectively. In a model based on the PCE and CACS, CCTA-derived data improved risk discrimination (C statistic improved from 0.764 to 0.779; P = .004) and risk reclassification (net reclassification improvement of 0.133 [95% CI, 0.031-0.165]), conferred a net correct upward reclassification of 14.2% in those with events and incorrectly classified 1.6% of participants not experiencing an event into a higher-risk category. Because of the low event rate in the cohort, reclassification mainly occurred in the group classified as at low risk (<5%) according to the PCE.

CONCLUSIONS AND RELEVANCE: Information on coronary atherosclerosis from CCTA modestly improved risk prediction beyond traditional risk factors and CACS in identifying individuals at risk of coronary events and in need of primary prevention.

Inter-arm blood pressure differences (IABPDs) can be caused by atherosclerosis. We investigated 29 921 men and women aged 50-64 years from the nationwide population-based Swedish CArdio Pulmonary bioImage Study (SCAPIS) to evaluate if IABPD is related to risk factors for atherosclerosis and can be used as a marker of atherosclerosis as evaluated by coronary artery calcium score, arterial segment involvement score on computed tomography, carotid ultrasound, and ankle-brachial index (ABI).

The overall prevalence of systolic IABPD at least 10 mmHg was 2110/29 921 (7.1%). Individuals with IABPD at least 10 mmHg were significantly ( P  < 0.001) older, more often women, had higher BMI, nonhigh-density lipoprotein cholesterol, triglycerides, SBP and DBPs, and were more likely to have diabetes. In unadjusted analyses, IABPD at least 10 mmHg was associated with presence of coronary atherosclerosis, with more carotid arteries with plaque, and with pathological ABI. These associations were largely attenuated after adjustment for cardiovascular risk factors (age, sex, nonhigh-density lipoprotein cholesterol, systolic BP, smoking, diabetes, and the use of BP lowering drugs). Only ABI retained significance after these adjustments.

In conclusion, a systolic IABPD of at least 10 mmHg in middle aged men and women is common in the general population, and can be used as a screening tool for subclinical atherosclerotic changes in coronary, carotid, and lower extremity arteries. However, these relationships were largely explained by correlations between IABPD and traditional cardiovascular risk factors.

Aims: Deleterious effects of Lipoprotein (a) (Lp(a)) might be mitigated by overall cardiovascular (CV) risk reduction. However, data on the relationship between increased Lp(a) and incident coronary heart disease (CHD) according to the distribution of modifiable CV risk factors (CVRF) at baseline are still scarce. We investigated the association between high Lp(a) and incident CHD in the general population, depending on the presence/absence of four major CVRFs (hypertension, diabetes, hypercholesterolemia, smoking) at baseline.

Methods and results: Overall 66 495 CHD-free individuals from eight European prospective population-based cohorts were included. The cohort was stratified according to CVRF burden at baseline in ‘0/1 CVRF’ (low risk; n = 41 770) and ‘≥2 CVRFs’ (increased risk; n = 24 725). Fine and Gray competing risk-adjusted models were calculated for the association between Lp(a) mass (<90th vs. ≥90th percentile (pctl.); cut-off 43.2 mg/dL) and future CHD events. During a median follow-up of 9.7 years, 3467 incident CHD events occurred. Despite being at very low absolute risk based on traditional CVRF, individuals with 0/1CVRF demonstrated a strong association between increased Lp(a) mass (≥90th pctl.) and future CHD events, which was comparable to the association observed among individuals with ≥2 CVRFs. The fully-adjusted sub-distribution Hazard Ratios [sHRs] for elevated Lp(a) were 1.38 (95% CI, 1.12–1.71) vs. 1.27 (95% CI, 1.10–1.46) in those having 0/1 vs. ≥2 CVRFs at baseline (P_interaction 0.50).

Conclusion: Among CHD-free subjects, high Lp(a) was related to adverse outcome even in individuals with no or only one CVRF at baseline, thereby generating substantial challenges in mitigating Lp(a)-associated CHD risk in very low risk populations.

Background and Aims: This study aimed to investigate the association between normal BP, (blood pressure [BP] 120–129/80–84 mmHg), and high normal BP, (BP 130–139/85–89 mmHg), compared to optimal BP, and risk of atrial fibrillation (AF).

Methods: A population-based cohort study was performed including inhabitants of Västerbotten County, Sweden, aged 30–60 years without AF at inclusion who participated in health examinations in 1988–2014. Approximately 40% of participants had ≥ 2 health examinations. The health examination included a questionnaire and measurement of BP, weight, height, and glucose. Cox regression with time-updated covariates was used to estimate the association between BP and AF risk. Restricted cubic spline analyses were performed.

Results: The cohort included 109,697 persons with 162,982 observations and a mean follow-up of 13.6 years. Incident AF was diagnosed in 5260 participants. We found an increased risk of incident AF associated with normal BP (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.01–1.27) and high normal BP (HR 1.23, 95% CI 1.10–1.38) compared to optimal BP after multivariable adjustment. Systolic BP and diastolic BP in 10 mmHg increments were associated with risk of incident AF, with HRs of 1.11 (95% CI 1.10–1.13) and 1.13 (95% CI 1.09–1.16), respectively, in multivariable models. A restricted cubic spline analysis indicated that the AF risk increased gradually with increasing systolic and diastolic BP.

Conclusion: Individuals with both normal BP and high normal BP have an increased risk of developing incident AF. The risk of AF increased gradually with increasing systolic and diastolic BP.

Aims: Helicobacter pylori (H. pylori) and its cytotoxin-associated gene A (CagA) have been associated with myocardial infarction (MI), but existing data are conflicting possibly due to limitations in study designs and lack of data on important confounders. The aim of this study was to determine whether H. pylori or CagA seropositivity is associated with incident MI, including MI phenotypes, and to describe temporal trends.

Methods: We used the Northern Sweden Health and Disease study, a prospective biobank with data from residents enrolled in a population-based cohort from health examinations between 1986 and 2006. A total of 826 first time MI cases with available blood samples from their index health examination were identified up to 2006. Each case was 1:2 matched with controls by age, sex, sample date and geographical area. Blood samples were analysed using ELISA to determine seroprevalence of H. pylori and CagA, which were then used to study the association with incident MI.

Results: The median age at baseline was 50 years, and 71% of participants were male. Seroprevalence of H. pylori and CagA was 46.5% and 32.1% in cases, respectively, compared to 43.7% and 30.6% in controls. Overall, H. pylori prevalence decreased over the study period. After multivariable adjustments, no significant association was observed between H. pylori seropositivity and incident MI (odds ratio: 1.15, 95% CI 0.94–1.42) nor between CagA-positive H. pylori and incident MI.

Conclusion: In a Swedish population-based cohort, no significant association was observed between H. pylori or CagA seropositivity and incidence of MI.

To investigate whether coronary artery disease (CAD) burden is associated with plasma levels of the myocardial biomarkers Troponin I (TropI) and NT-proBNP in a large population-based sample using a cross-sectional design. Coronary computerized tomography (CT) angiography was performed in 25,859 subjects without a history of atherosclerotic disease from SCAPIS study (age 50–65, 52% women). TropI and NT-proBNP were measured in plasma. Segment involvement score (SIS) was the primary exposure and TropI the primary outcome. Both SIS and coronary artery calcium score, were associated with TropI levels following adjustment for age, sex and multiple confounders (p < 0.001), with similar relationships in men and women. Proximal segments from all three coronary arteries were related to TropI levels independently of one another. Adding TropI to traditional risk factors marginally increased discrimination of atherosclerosis as compared to risk factors alone (C-statistics + 0.0005, p = 0.014). SIS was related also to NT-proBNP levels, mainly in men, but with lower estimates than TropI. The burden of CAD was related to TropI levels in both men and women. All three major coronary arteries contributed to this relationship. Adding TropI to traditional risk factors resulted in only marginally improved discrimination of coronary atherosclerosis.

Background and Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.

Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L).

Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024).

Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.

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.

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<0.01). With respect to snus, the use increased steeply up until 1999 among men, after which it persisted around 25% to 30% (26.2% in 2022), with percentage point changes between 6.6 and 13.4 compared with 1986 (p_within-group<0.01). The percentage of female snus users was extremely low in the first surveys but increased continuously over time, reaching a maximum of 13.0% in 2022 and a percentage point change of 12.5 since 1986 (p_within-group<0.01). Cigarette smoking—but not snus use—was more common in Norrbotten than in Västerbotten in 2022 (p_{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.

Objectives: Cystathionine-gamma-lyase (CSE) in the transsulfuration pathway generates hydrogen sulfide (H2S), suggested regulating cardiovascular function. The G1208T polymorphism in the CTH gene, rs1021737, has, in addition to MTHFR, been found to increase homocysteine, related to myocardial infarction (MI) risk. This study aimed, for the first time, to investigate the associations of the polymorphisms CTH G1208T, MTHFR C677T, and A1298C with the prospective risk of developing a fatal or non-fatal first MI.

Methods: This case-referent study included 545 cases later developing a first-ever MI and 1,054 referents from the Northern Sweden Health and Disease Study. Fatal MI was defined as death within 28 days after MI symptoms.

Results: Women, but not men, had a positive association between fatal MI and the CTH G1208T, odds ratio [95% confidence interval] 3.14 [1.16-8.54] for heterozygotes, and the dominant model 3.22 [1.22-8.51], and for the MTHFR A1298C heterozygotes 3.24 [1.26-8.34] and the dominant model 2.63 [1.06-6.50]. The MTHFR C677T polymorphism was not related to MI.

Conclusions: This study indicates that the minor alleles of CTH G1208T and MTHFR A1298C polymorphisms are associated with a higher risk for a fatal MI among women but not for non-fatal MI. No association was found in men.