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Cardiovascular Research 2001 50(2):186-196; doi:10.1016/S0008-6363(00)00319-9
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Copyright © 2001, European Society of Cardiology

Risk stratifiers for sudden cardiac death (SCD) in the community: primary prevention of SCD

Christine M Alberta,b,* and Jeremy N Ruskina

aCardiac Arrhythmia Service, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
bDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave East, Boston, MA 02215-1204, USA

* Corresponding author. Tel.: +1-617-732-8784; fax: +1-617-731-3843

Received 15 September 2000; accepted 4 December 2000

KEYWORDS Epidemiology; Sudden death; Ventricular arrhythmias


   1 Introduction
Top
 1 Introduction
2 Risk-stratifiers
 3 Conclusion
 References
 
There are currently 250,000 sudden cardiac deaths (SCD) in the United States every year constituting approximately 50% of all coronary heart disease (CHD) deaths [1]. Despite the decline in CHD mortality over the last decade, little proportionate change has been seen in the characteristics of CHD deaths. The majority of deaths are still sudden, occurring out-of-hospital and in the emergency room [2,3]. SCD is the most common cause of ischemic heart disease death in adults under the age of 65 years [2,3] and, therefore, is a major public health problem in the US and other industrialized countries [4,5]. Despite improved cardiopulmonary resuscitation, survival to hospital discharge is only 3–6% in unselected cases in major metropolitan centers. Even in cities with advanced EMS systems, such as in Seattle, USA, survival to hospital discharge still approaches only 30% among VF arrest victims, and is much lower for other types of cardiac arrest [6,7]. These percentages do not include those arrests that are not witnessed and for which resuscitation is not attempted. Undoubtedly, this percentage will improve with an increase in deployment of automated external defibrillators and public access defibrillation, however, it is clear from these statistics that any substantial reduction in SCD incidence will require effective preventive interventions.

In order to prevent SCD, we must be able to predict its occurrence. At this time, the presence and severity of underlying heart disease is the single most highly predictive risk factor for the future occurrence of SCD. The presence of overt CHD and/or CHF markedly increases the risk of SCD [8]. In the Framingham Study, pre-existing CHD was associated with a 2.8–5.3-fold increase in the risk of SCD and CHF was associated with a 2.6–6.2-fold increased risk [4]. Left ventricular dysfunction, in particular, is the most powerful independent predictor of SCD in patients with both ischemic and non-ischemic cardiomyopathy [9]. However, the majority of SCDs occur in those without known cardiac disease and not in the well-recognized high-risk subsets such as patients with a history of MI, severe LV dysfunction, or a prior cardiac arrest [10]. Approximately 55% of male and 63% of female SCD victims have no previous history of heart disease, and therefore SCD is often the initial manifestation of heart disease [11]. Therefore, SCD in this segment of the population must be addressed to impact significantly on the overall incidence of SCD.

Despite the large numbers of SCDs in the general population, the overall incidence is only 0.1% per year [12], and any population-based preventive intervention would have to be applied to 1000 people to prevent one sudden death. Therefore, to reduce the incidence of SCD, we must either accurately identify those at risk or develop safe, low-cost interventions that can be applied to the population at large. There are a number of population-based characteristics that appear to predict risk of SCD in the general population. These include traditional CHD risk factors, lifestyle and dietary habits, genetic influences, psychosocial factors, and triggers.


   2 Risk-stratifiers
Top
 1 Introduction
 2 Risk-stratifiers
3 Conclusion
 References
 
2.1 Demographics: age, sex, and race
The incidence of SCD increases markedly with age regardless of sex or race (Fig. 1). For example, the annual incidence for 50 year-old men is about 100 per 100,000 population compared to 800/100,000 for 75 year-old men (Fig. 1) [13]. However, the proportion of CHD deaths that are sudden decreases with age [11], and slightly more than half of all CHD deaths occurring outside of the hospital occur in those less than age 65 years [3]. At any age, women have a lower incidence of SCD than men. The incidence of SCD reaches major proportions beyond age 55, but is still less than 50% that of men at all decades of age [14]. This difference in SCD incidence does not appear to be attributable entirely to differences in major risk factors in the sexes or to a lower prevalence of CHD in women. Women still have 32% the rate of SCD as men after adjusting for known cardiac risk factors [8] and 25–50% that of men after myocardial infarction [14,15]. This suggests that women may have a relative protection against fatal ventricular arrhythmias in the setting of CHD. Consistent with this, we observed a 3:1 male/female ratio in a population of out-of-hospital cardiac arrest survivors referred to our institution, which was almost entirely due to an excess of men with CHD [16]. In the group without CHD, there were similar numbers of men and women. It appears that there is something about female gender that is protective against SCD even when overt CHD is present. Alternatively, women may have a higher proportional risk for non-sudden mechanisms of cardiac death.


Figure 1
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  		Fig. 1 The incidence of out-of-hospital cardiac arrest according to age, sex, and race in 6451 patients with a presumed basis for cardiac arrest in Chicago. Reproduced with permission from Ref. [13].

 
Racial differences in SCD have also been examined. African American men and women in two US cities experienced out-of-hospital cardiac arrest at an average age several years younger than their white counterparts. In all age groups, African Americans had higher rates (relative risk=1.3–2.8) of cardiac arrest than Caucasians [13,17] (Figure1). Also, survival rates after cardiac arrest were much lower for African Americans. In Chicago, the overall survival rate after an out-of-hospital cardiac arrest among African Americans was only 31% of that among whites [13]. These differences in survival were not entirely due to disparities in other recognized risk factors such as whether the arrest was witnessed and the initial rhythm at time of arrest. Even when response times were short and the initial rhythm was either ventricular fibrillation or ventricular tachycardia, African Americans were less likely to survive than Caucasians. The reasons for these racial differences have not been fully explained. As in all studies of racial differences, it is difficult to separate socioeconomic influences from a true genetic predisposition. Since economic status has been correlated with survival from cardiac arrest [18], it is possible that economic disadvantage accounts for part of this survival disadvantage.

2.2 Traditional coronary heart disease risk factors
Since approximately 80% of men who suffer SCD have underlying CHD, it follows that the standard CHD risk factors are predictive of SCD. Modifiable CHD risk factors that have been demonstrated to predict SCD in diverse cohorts include hypertension, hypercholesterolemia, diabetes, obesity, and smoking [10,4,19,20]. There are data to suggest that the prevalence of CHD among female SCD victims may be lower than their male counterparts [16,21] (Fig. 2). However, conventional CHD risk factors still appear to predict SCD in women [14]. Smoking, in particular, appears to be an important risk factor for SCD. In the Framingham study, the proportion of CHD deaths that were sudden increased with the number of cigarettes smoked [11]. Smoking appears to predispose both men and women to acute coronary thrombosis [22,23] and has been documented to be an important risk factor for recurrent cardiac arrest [24]. Importantly, smoking cessation is associated with a prompt reduction in the elevated risk for SCD [11,25].


Figure 2
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  		Fig. 2 Graphic illustration of the proportions of various types of underlying structural heart disease in consecutive female survivors of cardiac arrest referred for electrophysiologically guided therapy at Massachusetts General Hospital from 1978 to 1992. In this population, only 45% of women had underlying CHD compared to 80% of men. Reproduced with permission from Ref. [16].

 
Diabetes and hypertension are also strong risk factors for SCD, and diabetes is a particularly important risk factor in women [14]. These risk factors are associated with the presence of stable plaques and healed myocardial infarcts at autopsy [22,23]. Questions have been raised regarding whether diuretic use might account for part of the elevated risk associated with hypertension [10,26]. While the weight of the evidence suggests that low-doses are safe and beneficial in preventing CHD events [27], there is evidence that high doses of non-potassium sparing thiazide diuretics might increase the risk of cardiac arrest [28]. Serum cholesterol appears to be more strongly related to SCD below age 65 [14], and the TC/HDL ratio predisposes both men and post-menopausal women to acute plaque rupture [22,23]. The benefits of cholesterol lowing on total CHD events have been firmly established in randomized trials, and although none of the lipid lowering trials has examined SCD specifically, there is some evidence that there may be a reduction in the risk of SCD. The number of deaths occurring within 1 h of symptom onset was lower among the patients assigned to Simvastatin versus placebo (37 vs. 63) [29] in the Scandinavian Simvastatin Survival Study. However, this benefit was not specific to SCD since the same trend was seen for non-sudden mechanisms of death.

It must be noted that all of the risk factors discussed above predict CHD in general and are not specific for SCD. In addition, these risk factors no longer predict risk of SCD once overt CHD has been established [8]. Since specific risk factors for SCD (among those that predict the occurrence of CHD) have not been identified thusfar, primary prevention of SCD has centered on modifying these traditional CHD risk factors. The reduction in overall CHD mortality since the mid-1960s provides indirect evidence of the success of CHD risk factor modification [30]. Declines in the incidence rates of all manifestations of CHD including SCD suggest that the decline is due, at least in part, to measures of primary prevention centered on CHD risk factor modification.

2.3 Electrocardiographic predictors
The electrocardiogram can help to identify patients at increased risk of SCD. In the Framingham Heart Study, left ventricular hypertrophy on an EKG was associated with a 2–5-fold increased risk of SCD in men, but was only a modest risk factor in women [14]. Another important marker for SCD in men is an elevated heart rate [4,19,20]. This may be a reflection of autonomic balance, physical conditioning or both. In addition to heart rate and LVH, intraventricular conduction delays and non-specific ST-change are associated with an increased risk of SCD in both men and women [4]. Premature ventricular beats appeared to be an independent predictor of SCD in men, but are of only marginal significance in women [4]. These EKG abnormalities are associated with hypertension and the development of structural heart disease, and therefore it is not surprising that they are predictive of SCD. In fact, when absence of structural heart disease is clearly documented, PVCs alone do not confer an increased risk of SCD [31].

2.4 Multivariate risk indexes
Although the above CHD risk factors and EKG abnormalities are significantly associated with SCD, no single risk factor predicts with any accuracy who will die suddenly, and therefore the ability to identify specific individuals who are at high-risk of SCD is limited. In an attempt to identify high-risk individuals, multivariate risk indexes combining information on coronary risk factor status and EKG abnormalities have been created. In the Framingham Heart Study, a risk index was constructed from factors found to be independently associated with SCD over 38 years of follow-up (Fig. 3). The risk factors selected included age, ECG abnormality, systolic blood pressure, serum total cholesterol, vital capacity, smoking, relative weight and heart rate. Risk of SCD increased steeply with each decile of multivariate risk, and those in the upper quintile of multivariate risk had a 10-fold increased incidence of SCD compared to the lower quintile [11]. Moreover, 42 and 39% of all SCDs occurred among those in the upper decile of multivariate risk for men and women, respectively [14]. However, only 4.5% of the men classified as high-risk by this index actually died suddenly over 15 years [32] and, therefore, identification of those at high-enough risk to warrant a specific intervention remains poor. Clearly, continued research is needed to identify both the factors that specifically predispose to SCD among patients with and without overt CHD.


Figure 3
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  		Fig. 3 Risk of SCD according to decile of multivariate risk in men and women over 38 years of follow-up in the Framingham Heart Study. Variables included in the multivariate risk index include age, ECG abnormality (LVH, intraventricular conduction delay, non-specific ST abnormalities) systolic blood pressure, serum total cholesterol, vital capacity, smoking, relative weight and heart rate. Reproduced with permission from Ref. [14].

 
2.5 Nutritional risk factors
In addition to the traditional CHD risk factors, several nutritional factors appear to be associated with CHD mortality to a greater extent than non-fatal CHD, and some have been associated with SCD specifically. These risk factors may be more specific for SCD as opposed to other manifestations of CHD, and therefore, may have a selective effect on susceptibility to ventricular arrhythmias. There is basic research to suggest that some of these nutritional factors may reduce vulnerability to arrhythmogenic triggers such as ischemia or sympathetic stimulation. Such antiarrhythmic properties could result in a decreased risk of SCD without impacting upon underlying atherosclerosis.

Experimental data both in animals and at the cellular level suggest that n-3 polyunsaturated fatty acids (n-3 PUFAs) found primarily in fish may have antiarrhythmic properties [33,34]. Plausible mechanisms for these antiarrhythmic effects include modulation of Na, K+, and Ca2+ channels [33] and/or heart rate variability [35]. Small amounts of fish intake, such as one meal per week, have been inversely associated with cardiac mortality in several prospective cohorts [36–40] and with a reduced risk of SCD in two observational studies [41,42]. In a population based case-control study, both dietary intake of fish and red-blood cell n-3 fatty acid composition were associated with reduced risks of primary cardiac arrest [41]. We found similar results in a prospective cohort of 20,551 US male physicians [42]. In this cohort, dietary fish intake was associated with a reduced risk of sudden cardiac death without being associated with non-fatal MI. Both studies reported 50% reductions in risk associated with an intake of one fish-meal per week. These observational findings were recently supported by those of a randomized trial. In the GISSI-Prevenzione Trial [43], 11,324 patients surviving recent myocardial infarction were assigned at random using a two-by-two factorial design to fish-oil (850 mg; EPA/DHA 1:2) and vitamin E (300 mg). The patients assigned to n-3 PUFA had a significantly reduced risk of the primary endpoint (death, non-fatal MI, and non-fatal stroke) primarily due to a statistically significant 45% reduction in the risk of sudden death resulting in a significant 17% reduction in total death (Table 1). As in prior studies, there was no benefit on non-fatal events.


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  		Table 1 Overall efficacy of n-3 PUFA supplements in lowering various cardiovascular endpoints, including SCD, among 11,324 post myocardial infarction patients in the GISSI-Prevenzione Trial of 11,324 post-myocardial infarction patients (reproduced with permission from Ref. [43])a

 
In addition to eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) found in fish, there are other dietary sources of n-3 fatty acids. Alpha-linolenic acid is a long-chain n-3 fatty acid found in tofu, soybean and canola oil, nuts, and some other foods of plant origin that our bodies are able to elongate and desaturate into EPA and DHA [33]. Alpha-linolenic acid has not been studied directly in randomized trials, however, there has been one randomized secondary prevention trial [44,45] which evaluated the effect of a Mediterranean diet which is rich in {alpha}-linolenic acid. This trial found a 76% reduction in a combined endpoint of non-fatal MI and cardiac death in the group assigned to the Mediterranean diet despite no changes in serum lipids. Levels of alpha-linolenic acid were higher in the intervention group and there were no SCDs in this group compared to eight in the control group. Of course, there are many components to the Mediterranean diet, and it is impossible to know whether alpha-linolenic acid was the primary active component, however blood levels were correlated with outcome [45].

Alcohol is another dietary factor that may have a selective effect on risk of SCD. Heavy alcohol consumption (>5 drinks/day) is clearly associated with an increased risk of SCD [46,47], where such levels are not associated with increased risks of non-fatal MI. In contrast to heavy consumption, light-to-moderate levels of alcohol consumption may be associated with reduced risks [48]. In the prospective US Physicians Health Study [49], we found a significant U-shaped association between moderate alcohol consumption and subsequent SCD. Men who consumed 2–6 drinks per week at baseline had significant 60–79% reductions in risk of SCD compared to those who rarely or never consumed alcohol and compared to those who consumed 2 or more drinks per day (Fig. 4A). In contrast, the relationship of alcohol intake to non-sudden CHD death and non-fatal MI was linear and greater quantities of alcohol (1 or more drinks/day) were required to obtain the same benefit (Fig. 4B).


Figure 4
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  		Fig. 4 Age-adjusted and multivariate risk of SCD (A) and multivariate relative risk of non-fatal MI (B) according to level of alcohol intake among 21,527 men enrolled in the US Physicians' Health Study. Vertical bars represent 95% confidence intervals. *Relative risks are significantly less than one. Reproduced with permission from Ref. [49].

 
Magnesium intake may also be related to SCD rates. Magnesium and calcium are the principal minerals that determine water hardness [50], which has been inversely associated with regional differences in cardiovascular mortality [51]. In 1969, Anderson et al. [51] reported an inverse relationship between water hardness and SCD and no association with non-sudden cardiac death in Ontario, Canada. Epidemiologic studies in other countries have had similar findings [50]. Many elements have been investigated to explain these findings, but magnesium was found to correlate most closely (in an inverse fashion) with SCD rates [50]. In addition, autopsy studies have shown decreased myocardial magnesium content in people dying of SCD compared to controls who died of trauma [52,53], but it is unclear whether this is cause or effect. Currently there are no prospective cohort data assessing the association between magnesium intake and SCD. Along with magnesium, there are some data to support an antiarrhythmic effect of vitamin E [54]. Although vitamin E was not associated with a significant benefit on the primary combined endpoint in the GISSI-Prevenzione Trial [43], there was a benefit seen on SCD. However, this was not a pre-specified endpoint and other trials have not found similar findings [55].

2.6 Familial aggregation of SCD
It is well known that CHD tends to cluster in families, however, until recently, there has been little data on familial aggregation of SCD specifically. Two recent studies suggest that there may be a familial component to risk for SCD that is not explained by known environmental risk factors. In the population-based King County case-control study, a family history of MI or cardiac arrest in a first-degree relative was associated with a 57% increase in the risk of cardiac arrest independent of other risk factors [56]. The assessment of family history was retrospective in this study and therefore subject to recall bias, however, these findings have now been confirmed in a prospective study. In the Paris Prospective Study I, 118 SCDs were documented in 7746 men employed by the Paris Civil Service over an average of 23 years of follow-up [19]. Parental history of SCD was a strong independent risk factor for occurrence of SCD, but was not associated with the occurrence of fatal MI. Correspondingly, parental history of myocardial infarction was not associated with risk of SCD, but was a risk factor for the occurrence of fatal MI. The effect of parental history of SCD on SCD risk was cumulative. The relative risk was equal to 1.89 for those with one parent who died of SCD and 9.44 for those with two parents. This relationship between family history and SCD was similar in those above and below age 65. In addition, the age of the parent at the time of the SCD was directly correlated with the age of the progeny at the time of death (Fig. 5). The selectivity of the effect of family history of SCD on risk for SCD suggests that genetic or unknown environmental factors responsible for the familial aggregation may predispose to fatal arrhythmia rather than to CHD in general. At the present time these factors are unknown, but it raises the possibility that there may be genetic markers which could help to identify high-risk clusters within the lower risk segments of the general population.


Figure 5
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  		Fig. 5 Relationship between age of parent and age of progeny at time of sudden death among 7736 middle aged men enrolled in the Paris Prospective Study I of 7736. Reproduced with permission from Ref. [19].

 
2.7 Physical activity
Physical activity has both beneficial and adverse effects on risk for SCD. On the one hand, both vigorous and moderate physical activity have been consistently associated with reduced risks of non-fatal and fatal coronary heart disease in multiple epidemiologic investigations [57–59], and it appears that these benefits might also extend to SCD. The King County retrospective case-control study found a protective effect (RR=0.40) of 20 minutes or more of vigorous exertion per week on risk of primary cardiac arrest [60] and similar benefits (RR=0.27–0.34) with more moderate levels of physical activity such as walking [61]. Few prospective studies have examined sudden cardiac death specifically and rigorously and the results have been conflicting. The Framingham Heart Study [62,63] and the US Physicians' Health Study [64] found significant inverse associations between physical activity and total CHD, however, risk of SCD was not significantly reduced. In Framingham, the fraction of CHD deaths that were sudden actually increased with increasing levels of physical activity at 20 years of follow-up [63]. In contrast to these findings, the British Regional Health Service found a protective association between increasing levels of physical activity and SCD among British middle-aged men [20]. Moderate levels of physical activity were also associated with reduced risks of SCD, although the risks associated with vigorous activity were lower. The Multiple Risk Factor Intervention Trial also found a benefit of moderate levels of exercise on subsequent SCD risk but did not find an added effect of vigorous exercise [26]. Importantly, randomized trials of supervised rehabilitation with exercise have shown significant reductions in SCD rates [65].

Despite the long-term benefits of exercise, it is also well known that sudden cardiac death occurs with a higher than average frequency during or shortly after vigorous exertion [66]. In case report and autopsy series, 6–17% of all sudden cardiac deaths occur in association with acute exertion. Case-control and case-crossover studies have demonstrated that vigorous exertion can trigger cardiac arrest [60] and sudden cardiac death [64], however, a history of regular vigorous exertion diminishes the magnitude of this excess risk. In a retrospective case-control study in Seattle and King County [60], sedentary men had a relative risk of primary cardiac arrest of 56 during VE, compared to a relative risk of 5 among the men who participated in habitual vigorous exertion ≥140 minutes per week. These findings have subsequently been corroborated using a nested case-crossover design within the prospective Physicians' Health Study [61]. Men who exercised less than weekly had an extremely elevated excess risk of SCD associated with an episode of VE (RR=74.1) while those who exercised ≥5 times per week had a much lower risk (RR=10.9) (Table 2). However, even among the active men, the risk during exertion was still significantly elevated compared to the risk during periods of lesser exertion. Reassuringly, as has been found in prior studies, the absolute risk of sudden cardiac death during any particular episode of vigorous exertion was extremely low (1 sudden cardiac death per 1.51 million episodes).


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  		Table 2 Effect of habitual vigorous exercise on the risk of sudden death during vigorous exertion in the Physicians' Health Studya

 
The effect of exertion on plaque vulnerability and/or the sympathetic nervous system could account for both the transiently increased risk of SCD during a bout of exertion and the ability of habitual vigorous exercise to modify this excess risk. In one autopsy study of men who suffered SCD in association with CHD, plaque rupture was much more common in men who died suddenly during exertion than in those who died at rest [67]. Alternatively, chronic exercise may have beneficial effects on plaque stability through beneficial effect on lipids. In addition to effects on plaque vulnerability, exercise has direct electrophysiologic effects through the sympathetic nervous system. Acute bouts of exercise decrease vagal activity leading to an acute increase in susceptibility to ventricular fibrillation [68], whereas habitual exertion increases basal vagal tone resulting in increased cardiac electrical stability [69].

2.8 Psychosocial determinants
There are several psychosocial risk factors that both contribute to the development of cardiovascular disease and influence prognosis. Depression, anxiety, social isolation, and psychological stress have all been linked to an increase in cardiovascular mortality in diverse populations [70,71]. These factors are thought to exert their influence on cardiovascular mortality through increasing the risk of ventricular arrhythmia and SCD. Anxiety has been directly linked to SCD risk in two separate populations [72–74]. In the US Health Professionals Follow-up Study [74], high levels of phobic anxiety as measured by the Crown–Crisp Index were associated with a 3-fold increase in risk of CHD death which was due entirely to a 6-fold increase in SCD. Similar results were found in the Normative Aging Study [73]. Moreover, anxiety has not been associated with non-fatal myocardial infarction in any of these studies. Individuals with high levels of anxiety have reduced heart rate variability compared to normal subjects [74], which has been shown to independently predict mortality after myocardial infarction [75] and in a general population [76]. The mechanism is thought to be a reduction in vagal tone and increased sympathomimetic activity resulting in an increase in susceptibility to ventricular fibrillation.

Social supports may help to negate the risk associated with anxiety. Social isolation is a risk factor for the development of CHD in healthy populations manifesting primarily as cardiovascular death [70]. In addition, there are data to support a protective effect of social support against death in those with established CHD [70]. In addition to social isolation, depression is also associated with an increase in cardiovascular mortality among those with known CHD [71]. Depression has been associated with a 4-fold increase in mortality during the first 6 months after MI [77]. In one study, the risk was increased 30-fold when depressive symptoms occurred in the setting of frequent ventricular ectopy (>10 premature ventricular contractions per hour) [78]. In another study among patients with CHD, the incidence of documented ventricular tachycardia was higher among patients who also had depression [79]. These data suggest that similar to anxiety, depression may result in an increase susceptibility to ventricular arrhythmias.

In addition to the chronic effects of the psychosocial stresses outlined above, it appears that acute mental stress can trigger SCD. Acute increases in the incidence of SCD have been documented in populations suffering disasters such as earthquakes or wars [80–82]. One such example is that of the Northridge earthquake, one of the strongest earthquakes ever recorded in a major city in North America [80]. On the day of the earthquake, there was a sharp increase in the number of SCDs that were related to CHD (Fig. 6). This peak in incidence was accompanied by an unusually low incidence of such deaths in the week after the earthquake. This ‘natural experiment’ exemplifies how emotional stress may precipitate cardiac events in those who may be predisposed to such events. In addition to disasters, life stresses such as death of a spouse and loss of job have been associated with an increase in total mortality [83] and SCD [84] in healthy populations.


Figure 6
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  		Fig. 6 Daily numbers of sudden deaths related to atherosclerotic cardiovascular disease from January 10 through 23, 1994 in Los Angeles County. The Northridge earthquake occurred on January 17 and was associated with a peak in the incidence of SCD (24 cases, P<0.001). There was a decline in number of sudden deaths on each of the 6 days after the earthquake (P = 0.084). Reproduced with permission from Ref. [80].

 

   3 Conclusion
Top
 1 Introduction
 2 Risk-stratifiers
 3 Conclusion
References
 
The heterogeneity of the risk factors discussed above serves to emphasize the multifactorial nature of SCD. The risk of sudden cardiac death is not only a function of the underlying substrate, which for the majority of SCD victims is CHD, but is also dependent on the vulnerability of that substrate to arrhythmias and the frequency of exposure to arrhythmogenic triggers. All of the factors outlined above present possible avenues for future research and primary prevention. Several of these factors can be successfully modified with simple lifestyle and dietary changes, and therefore preventive strategies could be designed and applied to the general population at low cost and little risk. As discussed earlier, we have already seen a decline in total mortality related to CHD, which may be due at least in part to risk factor modification. An encouraging development is the recognition of dietary measures that appear to have antifibrillatory properties. Modification of this and other dietary factors should be tested in adequately sized randomized trials such as the GISSI-Prevenzione Trial. In addition to advances in prevention, a careful examination of the relationship of each risk factor to SCD has helped us to gain insight into the pathophysiologic mechanisms and circumstances underlying SCD in the general population.

However, despite progress in our understanding of the mechanisms underlying SCD in the general population, identification of those at very-high-risk remains poor. Although the predictors discussed above all impart an increased risk of SCD, they all have inadequate sensitivity and specificity for predicting SCD at the level of the individual. Therefore, one of the challenges for the future is to define predictors or methods that will allow the identification of very-high-risk individuals within the general population. The finding of a familial aggregation of SCD and recent advances in our understanding of primary arrhythmic disorders (e.g. the long QT interval and Brugada syndromes) may lead to the discovery of genetic factors that may help to identify high-risk clusters among those previously thought to be at low-risk within the general population. If we were able to identify very-high-risk individuals through genetic screening or other as yet unknown methods, then these individuals could be targeted for early intervention with the implantable-cardioverter defibrillator.

Time for primary review 34 days.


   References
Top
 1 Introduction
 2 Risk-stratifiers
 3 Conclusion
 References
 

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