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Prolonged heart rate-corrected QT interval (QTc) on the electrocardiogram (ECG) is maybe associated with the occurrence of cardiovascular diseases (CVD), but the evidence is inconsistent. Therefore, we investigated whether baseline prolongation of the QTc interval is associated with CVD morbidity and mortality and its subtypes and whether glucose tolerance modifies this association in a population-based cohort study with a mean follow-up of 10.8 years. We analyzed a glucose tolerance stratified sample (N = 487) from the longitudinal population-based Hoorn Study cohort (age 64 ± 7 years, 48% female). Cox regression was used to investigate the association between sex-specific baseline QTc quartiles and CVD morbidity and mortality. The risk was also estimated per 10 ms increase in QTc. All analyses were adjusted for age, sex, smoking status, systolic blood pressure, prevalent CVD, glucose tolerance status, hypertension and total cholesterol. In addition, stratified analyses were conducted for glucose tolerance status. During a mean follow-up of 10.8 years, 351 CVD events were observed. The adjusted hazard ratios (95% CI) for each 10 ms increase in QTc interval were 1.06 (95% CI: 1.02–1.10) for CVD, 1.06 (95% CI: 0.97–1.15) for acute myocardial infarction, 1.07 (95% CI: 1.01–1.13) for stroke, 1.12 (95% CI: 1.06–1.19) for heart failure, 1.04 (95% CI: 0.96–1.12) for peripheral arterial disease and 1.01 (95% CI:0.95–1.08) for coronary heart disease. Glucose tolerance status did not modify the association (P > 0.2). Prolongation of the QTc interval is associated with morbidity and mortality due to general CVD. Glucose tolerance status did not modify these associations. • QTc prolongation was associated with CVD morbidity and mortality • QTc prolongation was associated with stroke and heart failure • No association was found for coronary heart disease • No association was found for acute myocardial infarction • No association was found for peripheral arterial disease [ABSTRACT FROM AUTHOR]

Sudden cardiac death is responsible for 10% to 20% of all deaths in Europe. The current study investigates how well the risk of sudden cardiac death can be predicted. To this end, we validated a previously developed prediction model for sudden cardiac death from the Atherosclerosis Risk in Communities study (USA). Data from participants of the Copenhagen City Heart Study (CCHS) (n=9988) was used to externally validate the previously developed prediction model for sudden cardiac death. The model's performance was assessed through discrimination (C-statistic) and calibration by the Hosmer-Lemeshow goodness-of-fit (HL) statistics suited for censored data and visual inspection of calibration plots. Additional validation was performed using data from the Hoorn Study (N=2045), employing the same methods. During ten years of follow-up of CCHS participants (mean age: 58.7 years, 56.2% women), 425 experienced SCD (4.2%). The prediction model showed good discrimination for sudden cardiac death risk (C-statistic: 0.81, 95% CI: 0.79-0.83). Calibration was robust (HL statistic: P =0.8). Visual inspection of the calibration plot showed that the calibration could be improved. Sensitivity was 89.8%, and specificity was 60.6%. The positive and negative predictive values were 10.1% and 99.2%. Model performance was similar in the Hoorn Study (C-statistic: 0.81, 95% CI: 0.77-0.85 and the HL statistic: 1.00). Our study showed that the previously developed prediction model in North American adults performs equally well in identifying those at risk for sudden cardiac death in a general North-West European population. However, the positive predictive value is low. [ABSTRACT FROM AUTHOR]

• QTc prolongation was associated with atrial fibrillation. • QTc prolongation was associated with stroke and sudden cardiac death. • No association was found for myocardial infarction. Conflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease. To identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations. A systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models. Of the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33–2.12; I 2 = 69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08–1.50; I 2 = 38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26–3.39; I 2 = 78%); stroke (HR 1.59, 95% CI 1.29–1.96; I 2 = 45%); sudden cardiac death (HR 1.60, 95% CI 1.14–2.25; I 2 = 68%); and atrial fibrillation (HR 1.55, 95% CI 1.31–1.83; I 2 = 0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population. QTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population. [ABSTRACT FROM AUTHOR]

Background: The burden of sudden cardiac death (SCD) in the general population is substantial and SCD frequently occurs among people with few or no known risk factors for cardiac disease. Reported incidences of SCD vary due to differences in definitions and methodology between cohorts. This study aimed to develop a method for adjudicating SCD cases in research settings and to describe uniform case definitions of SCD in an international consortium harmonizing multiple longitudinal study cohorts.Methods: The harmonized SCD definitions include both case definitions using data from multiple sources (eg, autopsy reports, medical history, eyewitnesses) as well as a method using only information from registers (eg, cause of death registers, ICD-10 codes). Validation of the register-based method was done within the consortium using the multiple sources definition as gold standard and presenting sensitivity, specificity, accuracy and positive predictive value.Results: Consensus definitions of "definite," "possible" and "probable" SCD for longitudinal study cohorts were reached. The definitions are based on a stratified approach to reflect the level of certainty of diagnosis and degree of information. The definitions can be applied to both multisource and register-based methods. Validation of the method using register-information in a cohort comprising 1335 cases yielded a sensitivity of 74%, specificity of 88%, accuracy of 86%, and positive predictive value of 54%.Conclusions: This study demonstrated that a harmonization of SCD classification across different methodological approaches is feasible. The developed classification can be used to study SCD in longitudinal cohorts and to merge cohorts with different levels of information. [ABSTRACT FROM AUTHOR]

Background and Aims: Data on the prospective relationship of alcohol consumption at more moderate levels with systolic and diastolic function are scarce. We aimed to examine the prospective association of alcohol consumption with echocardiographic measures of cardiac structure and function, in individuals with and without type 2 diabetes (T2DM).Methods and Results: We included 778 participants from the Hoorn Study (aged 68.4 ± 7.2 years, 49% women), a population-based prospective cohort study, oversampled for people with impaired glucose metabolism or T2DM. Self-reported alcohol consumption was collected at baseline with a validated food-frequency questionnaire and categorized into: none (0/week), light (>0-≤30 g/week), light-to-moderate (>30-≤70 g/week), moderate (>70-≤140 g/week), and heavy drinkers (>140 g/week). Echocardiography was performed at baseline (N = 778) and after 8 years follow-up (N = 404). Multiple linear regression was used to study the association between alcohol consumption and echocardiographic measures (left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI)), adjusted for confounders. Moderate and heavy alcohol consumption were associated with a decreased LVEF of -3.91% (CI: -7.13;-0.69) for moderate and -4.77% (-8.18;-1.36) for heavy drinkers compared to light drinkers. No associations were found between alcohol consumption, LVMI and LAVI. Modified Poisson regression showed a trend that higher alcohol consumption amounts were associated with a higher risk of incident systolic dysfunction (LVEF≤50%) (P-for-trend 0.058).Conclusion: The findings provide longitudinal evidence that moderate and heavy alcohol consumption are associated with decreased LVEF and trend towards a higher risk of incident LV systolic dysfunction, compared to light drinkers. [ABSTRACT FROM AUTHOR]

Antibodies to the 65 kD isoform of glutamic acid decarboxylase (GAD65) have been associated with incident Type 2 Diabetes Mellitus, however results are inconsistent. To assess the association between GAD65 antibody positivity and incident Type 2 Diabetes Mellitus in a non-diabetic adult (≥18 years) population, in a systematic review and meta-analysis. A systematic literature search was conducted in Pubmed (MEDLINE) and Embase until January 14th, 2019. Included studies were 1) prospective studies on the association between GAD65 antibodies and incident Type 2 Diabetes Mellitus; 2) in a non-diabetic adult (≥18 years) population. To strengthen the review, unpublished data from 1302 Hoorn Study participants were included. Data extraction and quality assessment were performed independently by two observers. Ten studies were rated for methodological quality and seven were pooled using a random-effects meta-analysis, of which 2 strong, 2 moderate and 3 of low methodological quality. The pooled risk estimate of incident Type 2 Diabetes Mellitus for GAD65 antibody positivity, compared to GAD65 antibody negativity was 3.36 (95% CI: 1.9–5.9). This result was robust to sensitivity analyses. Heterogeneity between studies was significant with I2 statistic of 79% (p < 0.0001). However, excluding one study showed a decrease of I2 to 19% (p < 0.0001), explaining a large part of the heterogeneity. GAD65 antibody positivity was associated with an increased risk of future Type 2 Diabetes Mellitus in adults. • Ten papers on GAD65 antibodies and incident T2DM were identified from the literature. • In a meta-analysis, GAD65 antibody positivity was associated with >3 times increased risk of incident T2DM. • This finding was robust to sensitivity analyses. • One study explained a large part of the observed heterogeneity. [ABSTRACT FROM AUTHOR]