The current annual incidence of sudden cardiac death in the US is likely to be in the range of 180-250,000 per year. Coinciding with the decreased mortality from coronary artery disease, there is evidence pointing toward a significant decrease in rates of sudden cardiac death in the US during the second half of the twentieth century. However the alarming rise in prevalence of obesity and diabetes in the first decade of the new millennium both in the US and worldwide, would indicate that this favorable trend is unlikely to persist. We are likely to witness a resurgence of coronary artery disease and heart failure, as a result of which sudden cardiac death will have to be confronted as a shared and indiscriminate, worldwide public health problem. There is also increasing recognition of the fact that discovery of meaningful and relevant risk stratification and prevention methodologies will require careful prospective community-wide analyses, with access to large archives of DNA, serum and tissue that link with well-phenotyped databases. The purpose of this review is to summarize current knowledge of sudden cardiac death epidemiology. We will discuss the significance and strengths of community-wide evaluations of sudden cardiac death, summarize recent observations from such studies, and finally highlight specific potential predictors that warrant further evaluation as determinants of sudden cardiac death in the general population.

Background Early studies indicate that prolongation of the interval between the peak and end of the T wave (Tpeak to Tend, TpTe) on the 12-lead ECG, is a marker of ventricular arrhythmogenesis. However, community-based studies have not been conducted. Methods and Results TpTe and other ECG predictors were evaluated in the ongoing Oregon Sudden Unexpected Death Study based in the Portland, Oregon metropolitan area using a case-control design. Cases had sudden cardiac death (SCD), and were compared to living controls with coronary artery disease (CAD) from the same region. Analysis of TpTe and selected ECG intervals was limited to sinus rhythm 12-lead ECGs; for cases, these were obtained prior to and unrelated to SCD. Independent-samples t tests and multiple logistic regression were used. Mean TpTe was significantly greater in cases [89.4 (87.7 – 91.2) ms, p <0.0001; n=353, 66.6 (65.1 – 68.1) yr, 67% male] vs. controls [76.1 (74.8 – 77.4) ms; n=342, 64.7 (63.4 – 66.0) yr, 69% male)]. The other ECG intervals [Corrected QT interval (QTc), QRS duration (QRSD), and TpTe/QT ratio) were also significantly prolonged among cases vs. controls (p≤0.01). TpTe remained a significant predictor of SCD after adjusting for age, gender, QTc, QRSD and left ventricular function. Odds of SCD increased more with a one standard deviation increase in TpTe (12 ms) among subjects with prolonged QRSD [OR 3.49, 95% CI (2.06-5.91)] than with a one SD increase in TpTe among subjects with normal QRSD [OR1.96, 95% CI (1.65-2.32)]. TpTe remained significantly associated with SCD in subjects with normal QTc. Conclusions Prolongation of the TpTe interval measured in lead V5 was independently associated with SCD, with particular utility when the QTc was normal or not measurable due to prolonged QRSD.

Background-In a recent cohort study, prolongation of the corrected QT interval (QTc) was associated with an independent increased risk of sudden cardiac death (SCD). We evaluated determinants of prolonged QTc and the relationship of prolonged QTc to SCD risk among patients with coronary artery disease in the general population. Methods and Results-A case-control design was used. Cases were SCD patients with coronary artery disease among a metropolitan area of 1 000 000 residents (2002 to 2006); controls were area residents with coronary artery disease but no history of SCD. All cases were required to have an ECG suitable for QTc analysis before and unrelated to the occurrence of SCD. A total of 373 cases and 309 controls met criteria for analysis. Mean QTc was significantly longer in cases than in controls (450Ϯ45 versus 433Ϯ37 ms; PϽ0.0001). In a multivariate model, gender, diabetes mellitus, and QTc-prolonging drugs were significant determinants of QTc prolongation in controls. In a logistic regression model predicting SCD, diabetes mellitus (odds ratio, 1.97; 95% confidence interval, 1.32 to 2.96) and use of QTc-prolonging drugs (odds ratio, 2.90; 95% confidence interval, 1.92 to 4.37) were significant predictors of SCD among subjects with normal or borderline QTc. However, abnormally prolonged QTc in the absence of diabetes and QT-prolonging medications was the strongest predictor of SCD (odds ratio, 5.53; 95% confidence interval, 3.20 to 9.57). Conclusions-Diabetes mellitus and QTc-affecting drugs determined QTc prolongation and were predictors of SCD in coronary artery disease. However, idiopathic abnormal QTc prolongation was associated with 5-fold increased odds of SCD. A continued search for novel determinants of QTc prolongation such as genomic factors is likely to enhance risk stratification for SCD in coronary artery disease. (Circulation. 2009;119:663-670.)

The potential etiologic role of household pesticide exposures was examined in the Northern California Childhood Leukemia Study. A total of 162 patients (0-14 years old) with newly diagnosed leukemia were rapidly ascertained during 1995-1999, and 162 matched control subjects were randomly selected from the birth registry. The use of professional pest control services at any time from 1 year before birth to 3 years after was associated with a significantly increased risk of childhood leukemia [odds ratio (OR) = 2.8; 95% confidence interval (CI), 1.4-5.7], and the exposure during year 2 was associated with the highest risk (OR = 3.6; 95% CI, 1.6-8.3). The ORs for exposure to insecticides during the 3 months before pregnancy, pregnancy, and years 1, 2, and 3 were 1.8 (95% CI, 1.1-3.1), 2.1 (95% CI, 1.3-3.5), 1.7 (95% CI, 1.0-2.9), 1.6 (95% CI, 1.0-2.7), and 1.2 (95% CI, 0.7-2.1), respectively. Insecticide exposures early in life appear to be more significant than later exposures, and the highest risk was observed for exposure during pregnancy. Additionally, more frequent exposure to insecticides was associated with a higher risk. In contrast to insecticides, the association between herbicides and leukemia was weak and nonsignificant. Pesticides were also grouped based on where they were applied. Exposure to indoor pesticides was associated with an increased risk, whereas no significant association was observed for exposure to outdoor pesticides. The findings suggest that exposure to household pesticides is associated with an elevated risk of childhood leukemia and further indicate the importance of the timing and location of exposure.