In this population-based analysis, gender-based comparisons of potential risk factors for SCA identified two distinct clinical factors that were unique to women who suffer SCA. Women were significantly less likely than men to have severe LV dysfunction as a precursor to SCA. In addition, there was a significantly lower likelihood of women having an established diagnosis of CAD prior to SCA. These findings coincided with trends toward higher prevalence of DM and hypertension in women. There were no significant gender differences in the mean body mass index or prevalence of obesity, dyslipidemia, history of COPD/asthma, or left ventricular hypertrophy. After correction for age, significant gender differences disappeared for the gender-specific QTc categories which account for underlying male-female differences in the QTc interval, but remained for QTc measured continuously. This may imply that when the underlying longer QTc in women is taken into account, QTc does not appear to differentiate female from male SCA patients. With regard to presenting arrhythmia at the time of cardiac arrest, VF/VT was more commonly observed among men and PEA/asystole among women.
The lower rate of severe systolic LV dysfunction in females who suffer SCA is a finding with potentially important implications. Risk stratification based on degree of LV systolic dysfunction remains the major current and clinically utilized method of SCA risk stratification. The vast majority of patients who undergo ICD implantation have some form of cardiomyopathy with evidence of severe LV systolic dysfunction (LVEF≤35%). From community-based studies, we and others have previously reported that only 25-30% of SCAs occur in subjects who have severely reduced LV systolic function (3
). Using the existing guidelines for ICD implantation, we are likely to miss the opportunity to effectively risk stratify almost 70-75% of individuals who will suffer from SCA, and the current findings suggest that this number could be even higher for women.
The significantly lower prevalence of recognized CAD among women who suffer SCA is a novel finding in a population-based setting. There are several possible explanations. The fact that these results are consistent with published findings among hospitalized survivors of SCA (16
) would suggest that this reflects lower prevalence of significant CAD among female SCA cases. However, the possibility that women without CAD are more likely to be successfully resuscitated from SCA cannot be ruled out. Other potential explanations are that consideration of traditional risk factors may lead to underrecognition of CAD in women (17
); or that physicians pursue a less aggressive management approach to CAD in women than in men (18
); and/or there are higher rates of microvascular CAD (as opposed to epicardial CAD) among women (19
). While this phenomenon clearly warrants further investigation, CAD remains the condition most commonly associated with SCA. Symptoms related to CAD often prompt health care provider visits and an opportunity for risk stratification and initiation of drug therapy. Therefore it is also likely that the lower prevalence of recognized CAD among women impedes effective risk stratification and prevention of SCA in women.
It is of interest that a recent analysis of a Medicare population sample (1991-2005) reported that men were significantly more likely to undergo ICD implantation for both primary and secondary prevention of SCA (hazard ratio 3.15, 95% C.I. 2.86 to 3.47, and hazard ratio 2.44, 95% C.I. 2.30 to 2.59, respectively) (20
). This same gender disparity has also been reported in two other database analysis studies (21
). A subgroup analysis of the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) (23
) also reported lower rates of enrollment in women. However, women and men experienced a similar survival benefit from implantable cardioverter-defibrillator therapy. Therefore, development of methods that enhance SCA risk stratification in women should become an even higher priority. This need is underscored by our additional findings regarding the proportion of female SCA cases being higher than expected. In 2004, in contrast to earlier studies that have reported a 25:75 female:male ratio (24
), we observed that 40% of all cases were female (3
). Over a period of five years, these findings have been consistent in the Ore-SUDS with an average prevalence of 36%. While the reasons for this changing trend need to be evaluated in detail, one possibility is it corresponds to the altered sex distribution in prevalence of and mortality from CAD (26
If prevalence of severe LV systolic dysfunction in women is low and corresponds to lower rates of diagnosed coronary disease, what are the mechanisms of SCA in the majority of women? The established association between CAD risk factors such as smoking, hypertension and diabetes is common to both women and men (4
). However, there appear to be distinct differences in how SCA manifests in women. In a postmortem study, a subgroup of younger women tended to have plaque erosion with relatively little coronary arterial narrowing and less plaque calcium (27
). Furthermore, the majority of women (69% in an earlier prospective study (4
)) tend to have no history of cardiac disease prior to SCA (5
). This could be consistent with higher rates of vulnerable plaque rupture without pre-existing severe stenosis. There are other potential mechanisms. Based on higher rates of diastolic heart failure among women in the community, it has been suggested that women who suffer SCA could have higher prevalence of LV diastolic dysfunction (with preserved LV systolic dysfunction) vs. men (28
). Our findings that hypertension and DM, however, were more common in women compared to men (73 vs 62%, p=0.0001 and 39% vs 34%, p=0.03, respectively) would support the diastolic dysfunction hypothesis. There is evidence that common as well as rare gene variants may contribute to SCA and that at least some of these may be distributed more commonly among women. In community based studies, common variants in the SCN5A gene can increase susceptibility to SCA among women (30
), but not in men (31
). The majority (approximately 70%) of all reported cases of the familial or acquired long QT syndromes are women. Consistent with prior observations, the QTc was significantly longer in females (32
). Women were more likely to manifest with pulseless electrical activity compared to men, had higher rates of return of spontaneous circulation, but there were no differences in rates of survival to hospital discharge.
Based on their design, population-based studies of SCA have some limitations that relate mostly to the fact that all subjects analyzed may not have uniform information available. This is directly attributable to the fact that a large proportion of patients may have SCA without prior warnings or health care provider visits for cardiac testing. While prospective cohort studies could circumvent this limitation, the incidence of SCA is such that the large size of cohort required renders this approach unfeasible. However, in the present study availability of medical records were comparable in men and women (80% vs. 81%). Also, documentation of LV function was available in 307 (38%) men and 178 (39%) women, further decreasing the likelihood of gender bias in this regard. Nonetheless it remains possible that if the entire population were screened with echocardiograms, the overall prevalence of LV dysfunction may be different. Also, while subjects included in our analysis constituted the vast majority of SCA cases in the region, limiting ascertainment to individuals that underwent attempted resuscitation or were investigated by the medical examiner during the last two years of this five-year study may impact the generalizability of the findings to all SCA cases.