Independent Risk Factors For Sudden Cardiac Death Research Articles

Risk of Sudden Cardiac Death in Patients Undergoing Cancer Treatment

The risk of sudden cardiac death (SCD) in patients with cancer receiving cancer therapies is not well defined. In this study we aimed to (1) evaluate the risk of SCD during the first 6 months of cancer treatment and (2) identify risk factors (RFs) for SCD in patients who underwent active cancer treatment. The study population comprised 8,356 patients who received any cancer treatment at the University of Rochester Medical Center from 2011 to 2020. The primary end point was the occurrence of SCD within 6 months of cancer treatment. SCD was defined by using the modified Hinkle-Thaler classification. The mean age at the time of cancer treatment was 64 ± 14 years and 49% were women. All-cause mortality occurred in 834 patients (10%), of whom 51 (6%) were identified as SCD. The cumulative probability of SCD at 6 months was 0.6%. Age <74 years (0.042), history of congestive heart failure (0.058) and lung cancer (0.004) were identified as independent RFs for SCD in the multivariate Cox regression models. The cumulative probability of SCD at 6 months from cancer treatment initiation was significantly higher in patients with ≥2 RFs (1.6%) than in patients with 0 or 1 RF (0.5%) (log-rank p <0.001). In conclusion, our findings suggest that active cancer treatment is associated with SCD risk that is more pronounced in younger patients (< 74 years), patients with cancer and a history of heart failure, and those who underwent treatment for lung cancer. Future studies should address appropriate modalities for prevention and protection in this high-risk population.

High-Sensitivity Cardiac Troponin T Elevation in Hypertrophic Cardiomyopathy Is Associated With Ventricular Arrhythmias

ObjectiveTo investigate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) levels and sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). MethodsA referral HCM population with prospectively obtained hs-cTnT concentration from March 1, 2018, to April 23, 2020, was reviewed. Patients with end-stage renal disease or an abnormal hs-cTnT level not collected in an outpatient protocolled fashion were excluded. The hs-cTnT level was compared with demographic characteristics, comorbidities, conventional HCM-associated SCD risk factors, imaging, exercise testing, and prior cardiac events. ResultsOf 112 included patients, 69 (62%) had an elevated hs-cTnT concentration. The level of hs-cTnT correlated with known risk factors for SCD, including nonsustained ventricular tachycardia (P=.049) and septal thickness (P=.02). When patients were stratified by having a normal vs an elevated hs-cTnT concentration, patients with elevated hs-cTnT concentration were more likely to have experienced an implantable cardioverter-defibrillator discharge for ventricular arrhythmia, ventricular arrhythmia with hemodynamic instability, or cardiac arrest (incidence rate ratio, 2.96; 95% CI, 1.11 to 10.2). When sex-specific hs-cTnT cutoffs were removed, this association was no longer present (incidence rate ratio, 1.50; 95% CI, 0.66 to 3.60). ConclusionIn a protocolized, outpatient HCM population, hs-cTnT elevations were common and were associated with more arrhythmic expressivity of the HCM substrate as indicated by previous ventricular arrhythmias and appropriate implantable cardioverter-defibrillator shocks only when sex-specific hs-cTnT cutoffs were used. Further research should use different hs-cTnT reference values by sex to determine whether an elevated hs-cTnT value is an independent risk factor for SCD in patients with HCM.

Genetic risk factors for dilated cardiomyopathy

Aim. To study the diagnostic significance of genetic testing in patients with dilated cardiomyopathy (DCM), identify predictors of life-threatening ventricular tachyarrhythmias (VTAs) and assess adverse clinical outcomes in different genetic groups.Material and methods. The study included 126 unrelated patients with verified DCM as follows: 70 (55,6%) probands with criteria for familial DCM and 56 (44,4%) individuals with a probable hereditary component. All patients (age, 43,1±11,3 years; men, 92 (73%); left ventricular ejection fraction, 30,6±8,43%; left ventricular enddiastolic diameter, 68,3±8,36 mm; follow-up period — median, 49 months) receive a complex of diagnostic investigations, including genetic screening using nextgeneration sequencing, followed by verification of variants by the Sanger method.Results. Pathogenic and likely pathogenic genetic variants were found in 61 (48,4%) of 126 patients with DCM. The dominant mutations were titin-truncating variants (TTNtvs), identified in 16 individuals (12,7%), and variants of lamin A/C (LMNA), identified in 13 probands (10,3%). Mutations in the other 19 genes were found in 32 (25,4%) patients. The following primary endpoints were assessed: sudden cardiac death (SCD), episodes of VTA (sustained ventricular tachycardia/ventricular fibrillation) and appropriate shocks of implanted cardiac resynchronization therapy (CRT)/cardioverter defibrillators (CVD) devices. As a result of ROC analysis, the following independent risk factors for SCD were identified: mutations in the LMNA gene (AUC, 0,760; p=0,0001) and non-sustained ventricular tachycardia (cut-off heart rate ≥161 bpm: AUC, 0,788; p=0,0001). When comparing the phenotypes and genotypes of DCM, TTNtv genotype was associated with a lower prevalence of complete left bundle branch block (χ2=7,46; p=0,024), a lower need for CRT/CVD implantation (χ2=5,70; p=0,017) and more rare episodes of sustained ventricular tachycardia/ventricular fibrillation (χ2=30,1; p=0,0001) compared with LMNA carriers. Kaplan-Meier analysis showed the worst prognosis in carriers of LMNA mutations both in relation to life-threatening VTA (log rang χ2=88,5; p=0,0001) and in achieving all unfavorable outcomes (χ2=27,8; p=0,0001) compared with groups of genenegative individuals, carriers of TTNtv and other genotypes.Conclusion. The phenotypes of DCM with TTNtv did not significantly differ in the incidence of VTAs and adverse outcomes compared with the gene-negative group and other genotypes (with the exception of LMNA). The contribution of the associations of LMNA mutations with VTAs on prognosis was confirmed, which shows the important role of LMNA genotype diagnosis for SCD risk stratification in patients with DCM.

Left ventricular hypertrophy and sudden cardiac death

Sudden cardiac death (SCD) is among the leading causes of death worldwide, and it remains a public health problem, as it involves young subjects. Current guideline-directed risk stratification for primary prevention is largely based on left ventricular (LV) ejection fraction (LVEF), and preventive strategies such as implantation of a cardiac defibrillator (ICD) are justified only for documented low LVEF (i.e., ≤ 35%). Unfortunately, only a small percentage of primary prevention ICDs, implanted on the basis of a low LVEF, will deliver life-saving therapies on an annual basis. On the other hand, the vast majority of patients that experience SCD have LVEF > 35%, which is clamoring for better understanding of the underlying mechanisms. It is mandatory that additional variables be considered, both independently and in combination with the EF, to improve SCD risk prediction. LV hypertrophy (LVH) is a strong independent risk factor for SCD regardless of the etiology and the severity of symptoms. Concentric and eccentric LV hypertrophy, and even earlier concentric remodeling without hypertrophy, are all associated with increased risk of SCD. In this paper, we summarize the physiology and physiopathology of LVH, review the epidemiological evidence supporting the association between LVH and SCD, briefly discuss the mechanisms linking LVH with SCD, and emphasize the need to evaluate LV geometry as a potential risk stratification tool regardless of the LVEF.

Abstract 14760: Myocardial Scarring by Magnetic Resonance Predicts Sudden Cardiac Death in Pediatric Patients With Hypertrophic Cardiomyopathy

Introduction: Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) has been shown to be an independent predictor of sudden cardiac death (SCD) in adults with hypertrophic cardiomyopathy (HCM). The clinical significance of LGE in pediatric HCM patients is unknown. Hypothesis: LGE improves the SCD risk prediction in children with HCM. Methods: We retrospectively analyzed the CMR images and reviewed the outcomes pediatric HCM patients. Results: Amongst the 720 patients from 30 centers, 73% were male, with a mean age of 14.2±4.8 years. During a mean follow up of 2.6±2.7 years (range 0-14.8 years), 34 experienced an episode of SCD or equivalent. LGE (Figure 1A) was present in 34%, with a mean burden of 14±21g, or 2.5±8.2g/m2 (6.2±7.7% of LV myocardium). The presence of ≥1 adult traditional risk factor (family history of SCD, syncope, LV thickness &gt;30mm, non-sustained ventricular tachycardia on Holter) was associated with an increased risk of SCD (HR=4.6, p&lt;0.0001). The HCM Risk-Kids score predicted SCD (p=0.002). The presence of LGE was strongly associated with an increased risk (HR=3.8, p=0.0003), even after adjusting for traditional risk factors (HR adj =3.2, p=0.003) or the HCM Risk-Kids score (HR adj =3.5, p=0.003). Furthermore, the burden of LGE was associated with increased risk (HR=2.1/10% LGE, p&lt;0.0001). LGE burden remained independently associated with an increased risk for SCD after adjusting for traditional risk factors (HRadj=1.5/10% LGE, p=0.04) or HCM Risk-Kids (HRadj=1.9/10% LGE, p=0.0018, Figure 1B). The addition of LGE burden improved the predictive model using traditional risk markers (C statistic 0.67 vs 0.77, p=0.003) and HCM Risk-Kids (C statistic 0.68 vs 0.74, p=0.045). Conclusions: Quantitative LGE is an independent risk factor for SCD in pediatric patients with HCM and improves the performance of traditional risk markers and the HCM Risk-Kids Score for SCD risk stratification in this population.

Heartbeat: time to treat the whole patient, not just the valve, when calcific aortic stenosis is present

A key consideration in timing of aortic valve replacement (AVR) for patients with aortic stenosis (AS) is whether there is an increased risk of sudden cardiac death (SCD) that might...

Abstract P110: High Serum Urate Levels are Associated With an Increased Risk for Sudden Cardiac Death in the Reasons for Geographic and Racial Differences in Stroke (regards) Study

Background: Higher serum urate (SU) levels were shown to causally increase the risk for sudden cardiac death (SCD) in a Mendelian randomization analysis of white adults, most of whom had coronary heart disease (CHD). It is unclear if these results are generalizable to more racially diverse adults without CHD. Objective: To assess the risk for SCD and incident CHD associated with SU levels in adults without a history of CHD using data from a large, population-based cohort of US black and white men and women ≥45 years of age, the REason for Geographic And Racial Differences in Stroke (REGARDS) study. Methods: We conducted a case-cohort analysis of REGARDS study participants without a history of CHD at baseline between 2003 and 2007. Participants were followed for SCD or incident CHD (i.e., myocardial infarction or CHD death excluding SCD) from baseline through December 31, 2013. Baseline SU levels were measured in a random sample of participants (n=840) and among 235 participants with SCD and 851 participants with incident CHD. Results: Participants with higher SU levels were older and more likely to be black and male. The crude hazard ratio (95%CI) per 1 mg/dL higher SU level was 1.26 (1.14, 1.40) for SCD and 1.17 (1.09, 1.26) for incident CHD. Analyses modeling SU levels using splines supported that these associations were linear. After multivariable adjustment, higher SU levels remained associated with an increased risk for SCD, but not for incident CHD ( Table ). There was no effect modification in the association of SU levels with SCD or incident CHD by either age, gender, race or chronic kidney disease. However, the increased risk for SCD associated with higher SU levels was present in whites but not among blacks. Limitations: The study has limited statistical power for subgroup comparisons. Race differences in the association between SU levels and SCD require further investigation. Conclusions: In adults without a history of CHD, higher SU levels appear to be an independent risk factor for SCD, but no association was detected with incident CHD.

Antihypertensive therapy and sudden cardiac death, should we expect the unexpected?

Hypertension (HTN) and sudden cardiac death (SCD) constitute major public health problems accounting for millions of deaths each year worldwide. Both HTN and HTN-induced left ventricular hypertrophy (LVH) have been shown to be independent risk factors for SCD. However, the association between antihypertensive pharmacotherapy and risk of SCD has been under-investigated. Given that antihypertensive pharmacotherapy effectively reduces overall cardiovascular mortality, it would be expected to protect patients from SCD. Nevertheless, available data demonstrate that antihypertensive medications (primarily thiazide diuretics), while effective in reducing the incidence of myocardial infarction, do not confer protection from SCD. The purpose of this review was to present the relationship between HTN, LVH, and SCD and to describe the potential association between antihypertensive pharmacotherapy and risk of SCD.

Dialysis modality-related disparities in sudden cardiac death: hemodialysis versus peritoneal dialysis.

BackgroundPatients require risk stratification and preventive strategies for sudden cardiac death (SCD) based on the dialysis modality because the process of dialysis is a risk factor for SCD. This study aimed to compare the risk of SCD in patients undergoing hemodialysis (HD) versus peritoneal dialysis (PD).MethodsPatients on HD and PD were included in the end-stage renal disease registry of the Korean Society of Nephrology between 1985 and 2017. The incidence and associated factors of SCD were analyzed based on the dialysis modality.ResultsOf 132,083 patients, 34,632 (26.2%) died during 94.8 ± 73.6 months of follow-up. In patients on HD and PD, 22.2% and 19.6% of total deaths were SCDs. In the propensity score-matched population, SCD accounted for 21.7% and 19.6% of total deaths in patients on HD and PD, respectively. HD was independently associated with SCD even after adjusting for age and significant comorbidities. Hypertension, coronary artery disease, and congestive heart failure, and age at the time of death < 65 years were independent risk factors for SCD in patients on HD but not in those on PD. Diabetes was significantly associated with SCD regardless of the dialysis modality.ConclusionCompared with patients on PD, Korean patients on HD have a higher risk of SCD, which is attributable to cardiac comorbidities.

Association of HIV Infection and Antiretroviral Therapy With Sudden Cardiac Death.

HIV infection potentially increases coronary artery disease and heart failure risks. However, the association between HIV infection and sudden cardiac death (SCD) has not been extensively studied. This nationwide cohort study aimed to determine SCD risks in Taiwanese patients with and without HIV infection. Adult people living with HIV/AIDS (PLWHA) since January 1, 2003, were identified from the Taiwan Centers for Disease Control HIV surveillance system. HIV-infected individuals were defined as positive HIV-1 Western blot. A control cohort without HIV infection, matched for age and sex, was selected for comparison from the Taiwan National Health Insurance Research Database. All patients were followed up until SCD, mortality for another cause, or till December 31, 2014. A time-dependent Cox proportional hazards model was used to determine the association of HIV and antiretroviral therapy (ART) with SCD. During a mean 5.86-year follow-up, 5342 (4.40%) of 121,530 patients (24,306 PLWHA and 97,224 matched controls) died; among them, 150 (0.12%) died of SCD. Among 150 SCD events, 97 (64.7%) and 53 (33.3%) occurred in PLWHA and controls, respectively, which corresponded to incidences of 68.31 in PLWHA and 9.31 per 100,000 person-years in controls (P < 0.001). After adjusting for age, sex, and comorbidities, HIV infection was an independent risk factor for SCD (adjusted hazard ratio, 8.15; 95% confidence interval: 5.58 to 11.90). SCD incidence was significantly lower in PLWHA receiving ART (adjusted hazard ratio 0.53; 95% confidence interval: 0.32 to 0.87). HIV infection is an independent risk factor for SCD. SCD rates are low in PLWHA receiving ART.

Prolonged Tpeak -Tend interval is a risk factor for sudden cardiac death in adults with congenital heart disease.

ObjectiveAdult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). However, methods for risk stratification are not yet well‐defined. The Tpeak‐Tend (TpTe) interval, a measure of dispersion of ventricular repolarization, is a risk factor for SCD in non‐ACHD patients. We aim to evaluate whether TpTe can be used in risk stratification for SCD in ACHD patients.DesignFrom an international multicenter cohort of 25 790 ACHD patients, we identified all SCD cases. Cases were matched to controls by age, gender, congenital defect, and (surgical) intervention.Outcome MeasuresTpTe was measured on a standard 12‐lead ECG. The maximum TpTe of all ECG leads (TpTe‐max), mean (TpTe‐mean), and TpTe dispersion (maximum minus minimum) were obtained. Odds ratios (OR) for SCD cases vs controls were calculated using conditional logistic regression analysis.ResultsECGs were available for 147 cases (median age at death 33.5 years (quartiles 26.2, 48.7), 66% male) and 267 controls. The mean TpTe‐max was 97 ± 24 ms in cases vs 84 ± 17 ms in controls (P < .001); TpTe‐mean was 70 ± 16 vs 63 ± 10 ms (P < .001); and dispersion was 51 ± 22 ms vs 41 ± 16 ms (P = .02), respectively. Assessing each ECG lead separately, TpTe in lead aVR predicted SCD most accurately. TpTe in lead aVR was 71 ± 23 ms in cases vs 61 ± 13 ms in controls (P < .001). After adjusting for impaired ventricular function, heart failure symptoms, and prolonged QRS duration, the OR of SCD of TpTe in lead aVR at an optimal cutoff of 80 ms was 5.8 (95% CI 2.7‐12.4, P < .001).ConclusionsThe TpTe interval is associated with SCD in ACHD patients. Particularly, TpTe in lead aVR can be used as an independent risk factor for SCD in ACHD patients and may, therefore, add precision to current risk prediction models.

TpTe and TpTe/QT: novel markers to predict sudden cardiac death in ESRD?

ABSTRACTIntroduction:Reliable markers to predict sudden cardiac death (SCD) in patients with end stage renal disease (ESRD) remain elusive, but echocardiogram (ECG) parameters may help stratify patients. Given their roles as markers for myocardial dispersion especially in high risk populations such as those with Brugada syndrome, we hypothesized that the Tpeak to Tend (TpTe) interval and TpTe/QT are independent risk factors for SCD in ESRD.Methods:Retrospective chart review was conducted on a cohort of patients with ESRD starting hemodialysis. Patients were US veterans who utilized the Veterans Affairs medical centers for health care. Average age of all participants was 66 years and the majority were males, consistent with a US veteran population. ECGs that were performed within 18 months of dialysis initiation were manually evaluated for TpTe and TpTe/QT. The primary outcomes were SCD and all-cause mortality, and these were assessed up to 5 years following dialysis initiation.Results:After exclusion criteria, 205 patients were identified, of whom 94 had a prolonged TpTe, and 61 had a prolonged TpTe/QT interval (not mutually exclusive). Overall mortality was 70.2% at 5 years and SCD was 15.2%. No significant difference was observed in the primary outcomes when examining TpTe (SCD: prolonged 16.0% vs. normal 14.4%, p=0.73; all-cause mortality: prolonged 55.3% vs. normal 47.7%, p=0.43). Likewise, no significant difference was found for TpTe/QT (SCD: prolonged 15.4% vs. normal 15.0%, p=0.51; all-cause mortality: prolonged 80.7% vs. normal 66.7%, p=0.39).Conclusions:In ESRD patients on hemodialysis, prolonged TpTe or TpTe/QT was not associated with a significant increase in SCD or all-cause mortality.

131 Left ventricular indexed mass associated with ventricular arrhythmias in patients with hypertrophic cardiomyopathy – a tertiary centre mri registry

BackgroundHypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition. Multiple factors have been identified towards high risk of sudden cardiac death (SCD) as outlined in the ESC guidelines. LV wall...

Risk of Sudden Cardiac Death in Chronic Kidney Disease

The review discusses the epidemiology and the possible underlying mechanisms of sudden cardiac death (SCD) in chronic kidney disease (CKD), and highlights the unmet clinical need for noninvasive risk stratification strategies in these patients. Although renal dysfunction shares common risk factors and often coexists with atherosclerotic cardiovascular disease, the presence of renal impairment increases the risk of arrhythmic complications to an extent that cannot be explained by the severity of the atherosclerotic process. Renal impairment is an independent risk factor for SCD from the early stages of CKD; the risk increases as renal function declines and reaches very high levels in patients with end-stage renal disease on dialysis. Autonomic imbalance, uremic cardiomyopathy, and electrolyte disturbances likely play a role in increasing the arrhythmic risk and can be potential targets for treatment. Cardioverter defibrillator treatment could be offered as lifesaving treatment in selected patients, although selection strategies for this treatment mode are presently problematic in dialyzed patients. The review also examines the current experience with risk stratification tools in renal patients and suggests that noninvasive electrophysiological testing during dialysis may be of clinical value as it provides the necessary standardized environment for reproducible measurements for risk stratification purposes.

Obstructive Sleep Apnea and the Risk of Sudden Cardiac Death: A Longitudinal Study of 10,701 Adults

This study sought to identify the risk of sudden cardiac death (SCD) associated with obstructive sleep apnea (OSA). Risk stratification for SCD, a major cause of mortality, is difficult. OSA is linked to cardiovascular disease and arrhythmias and has been shown to increase the risk of nocturnal SCD. It is unknown if OSA independently increases the risk of SCD. We included 10,701 consecutive adults undergoing their first diagnostic polysomnogram between July 1987 and July 2003. During follow-up up to 15 years, we assessed incident resuscitated or fatal SCD in relation to the presence of OSA, physiological data including the apnea-hypopnea index (AHI), and nocturnal oxygen saturation (O 2 sat) parameters, and relevant comorbidities. During an average follow-up of 5.3 years, 142 patients had resuscitated or fatal SCD (annual rate 0.27%). In multivariate analysis, independent risk factors for SCD were age, hypertension, coronary artery disease, cardiomyopathy or heart failure, ventricular ectopy or nonsustained ventricular tachycardia, and lowest nocturnal O 2 sat (per 10% decrease, hazard ratio [HR]: 1.14; p = 0.029). SCD was best predicted by age >60 years (HR: 5.53), apnea-hypopnea index >20 (HR: 1.60), mean nocturnal O 2 sat <93% (HR: 2.93), and lowest nocturnal O 2 sat <78% (HR: 2.60; all p < 0.0001). In a population of 10,701 adults referred for polysomnography, OSA predicted incident SCD, and the magnitude of risk was predicted by multiple parameters characterizing OSA severity. Nocturnal hypoxemia, an important pathophysiological feature of OSA, strongly predicted SCD independently of well-established risk factors. These findings implicate OSA, a prevalent condition, as a novel risk factor for SCD.

Risk Factors for Sudden Cardiac Death in Post-Menopausal Women

The aim of this study was to estimate the annual incidence rate of sudden cardiac death (SCD) and to identify risk factors for SCD in post-menopausal women. With the aging U.S. population, post-menopausal women now have the greatest population burden of cardiovascular disease including SCD. We examined 161,808 women who participated in the Women's Health Initiative clinical trials and observational study. The women were recruited at 40 clinical sites across the United States, enrolled between 1993 and 1998, and followed until August 2009. Our primary endpoint is incident SCD, defined as death occurring within 1 h of symptom onset or within 1 h after the participant was last seen without symptoms and death that occurred in the absence of a potentially lethal non-coronary disease process. Four hundred eighteen women experienced adjudicated SCD. The incidence rate of SCD was 2.4/10,000 women/year (95% confidence interval: 2.2 to 2.7). We identified the following independent risk factors for SCD: older age, African-American race, tobacco use, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, history of heart failure, diabetes, history of myocardial infarction, previous carotid artery disease, and hypertension. Population-attributable fractions were greatest for hypertension, waist-to-hip ratio, and myocardial infarction. Besides traditional risk factors for coronary heart disease, risk factors for sudden cardiac death in post-menopausal women include African-American race, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, and heart failure. Nearly one-half of women who experienced sudden cardiac death had no previous diagnosis of coronary heart disease.

Plasma Biomarkers for Prediction of Sudden Cardiac Death

Sudden cardiac death (SCD) accounts for most cardiovascular deaths in the United States, claiming an estimated 300 000 lives per year.1 Despite intense efforts to develop resuscitation techniques, survival rates are still low, at ≈5%.2 This has led to a renewed focus in this field directed toward optimizing risk prediction to identify the candidate that would qualify for prophylactic or preventive interventions.3 At present, the clinical risk stratification is largely limited to the use of left ventricular ejection fraction (LVEF) for identifying primary prophylaxis candidates, but specificity of this predictor is modest.4 Moreover, the absolute numbers of these high-risk patients in the general population are low. Instead, the highest prevalence of SCD is likely observed among previously asymptomatic individuals, even though it is well-known that coronary artery disease (CAD) is present in most SCD cases.5 This underscores the need for the development of risk stratification models that can be applied to the general population where the largest health benefit is likely to be realized. The underpinnings of SCD are complex, and it is reasonable to believe that the risk stratification instrument of the future is likely to involve other components beyond clinical risk markers. Novel genomic variants show promise but are still in early phases of development as risk stratification targets. However, the “unbiased” approaches made possible through genomewide association studies have led to the recent identification of specific genetic variants that could predict SCD.6,7 This has reignited the interest in plasma biomarkers as a means for risk stratification. This article will review the emerging evidence and role of plasma biomarkers in predicting SCD in the general population and suggest a blueprint for future studies of potential utility. ### Uniform Definition of SCD Given the complexity and dynamic nature of the condition, there has been some variability …

Foreword

The aim of this study was to estimate the annual incidence rate of sudden cardiac death (SCD) and to identify risk factors for SCD in post-menopausal women.With the aging U.S. population, post-menopausal women now have the greatest population burden of cardiovascular disease including SCD.We examined 161,808 women who participated in the Women's Health Initiative clinical trials and observational study. The women were recruited at 40 clinical sites across the United States, enrolled between 1993 and 1998, and followed until August 2009. Our primary endpoint is incident SCD, defined as death occurring within 1 h of symptom onset or within 1 h after the participant was last seen without symptoms and death that occurred in the absence of a potentially lethal non-coronary disease process.Four hundred eighteen women experienced adjudicated SCD. The incidence rate of SCD was 2.4/10,000 women/year (95% confidence interval: 2.2 to 2.7). We identified the following independent risk factors for SCD: older age, African-American race, tobacco use, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, history of heart failure, diabetes, history of myocardial infarction, previous carotid artery disease, and hypertension. Population-attributable fractions were greatest for hypertension, waist-to-hip ratio, and myocardial infarction.Besides traditional risk factors for coronary heart disease, risk factors for sudden cardiac death in post-menopausal women include African-American race, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, and heart failure. Nearly one-half of women who experienced sudden cardiac death had no previous diagnosis of coronary heart disease.

Risk factors for sudden cardiac death in middle-aged British men.

Risk factors specific to sudden cardiac death (SCD), ie, death within 1 hour after onset of symptoms, have been poorly identified, although recent findings from the present study incriminate heavy drinking and elevated heart rate. This paper examines the relations between a wide range of established and potential risk factors for ischemic heart disease (IHD) and SCD to identify independent risk factors for SCD and factors that might particularly or specifically relate to SCD. We present a prospective study of a cohort that was drawn from general practices in 24 British towns of 7735 middle-aged men who were followed up for 8 years. During 8 years of follow-up, the men experienced 488 major IHD events (nonfatal and fatal), of which 117 (24%) were classified as SCD. Age, preexisting IHD, arrhythmia, systolic blood pressure, blood cholesterol, elevated heart rate (> or = 90 beats per minute), physical activity (all, P < .05), and, to a lesser extent, smoking (P = .06), HDL cholesterol (P < .07), and elevated hematocrit (> or = 46%, P < .09) emerged as independent risk factors for SCD after adjustment for a wide range of factors. Diabetes was not found to be associated with SCD, and forced expiratory volume in 1 second, body mass index, white blood cell count, and antihypertensive drugs were not associated with risk of SCD after adjustment. When examined in relation to non-sudden IHD deaths and nonfatal myocardial infarction, elevated heart rate, heavy drinking, and arrhythmia emerged as factors that appear to be specific or particular to SCD. These three factors and age and blood cholesterol were associated with an increased risk of SCD in men both with and without preexisting IHD. Physical activity, systolic blood pressure, and current smoking were associated with SCD only in men without preexisting IHD. HDL cholesterol and hematocrit were strong predictors of SCD only in men with preexisting IHD. Three risk factors appear to be specific or particular to the risk of SCD, and these and other risk factors operate differently in patients with versus those without preexisting IHD. These findings have implications for the causes and prevention of SCD.