A low-risk lifestyle (not smoking, regular exercise, prudent diet and healthy weight) was linearly and inversely associated with risk of SCD among women. Women at low-risk for all 4 lifestyle factors had a 92% lower risk of SCD compared to women at low-risk for 0 lifestyle factors. If these associations are causal, hypothetically, 81% of SCD within this cohort may have been prevented if all women adhered to the low-risk lifestyle. Among women without diagnosed CHD, where the majority of SCDs occur, it is possible that 79% of SCD may be attributed to unhealthy lifestyle practices.
Primary prevention of SCD in women is of particular concern. Compared with men, women are 50% less likely to have severe left ventricular dysfunction and 66% less likely to be diagnosed with CHD before SCD, and therefore are less likely to meet current guideline recommendations for beta-blocker therapy or prophylactic ICD placement.42
Prevention efforts that can be applied across broader populations, such as healthy lifestyle practices, are crucial to prevent SCD, particularly among women.
Substantial evidence supports the benefit of lifestyle modification for the prevention of SCD. Smoking cessation has been associated with reductions in SCD risk,43
while regular physical activity has been inversely associated with lower risk of SCD in observational studies.8, 9
A Mediterranean-style diet was associated with lower risk of CVD in clinical trials44
and observational studies45
. The association between the Mediterranean diet and CVD appears stronger for fatal, compared to nonfatal events31
, which may be driven partially through protection against ventricular arrhythmias and SCD. Furthermore, several key components of a Mediterranean-style diet, including nuts, fish and omega-3 fats, and moderate intake of alcohol, have been associated with lower risk of SCD.10-14, 32, 33
Consistent with prior evidence, we found a strong inverse association between the aMed diet score and risk of SCD.
The J-shaped association between BMI and risk of SCD parallels the association with all-cause mortality.46
The elevated risk among women with BMI <21.0 is likely biased by reverse causation from preexisting disease, residual confounding by smoking, and effect modification by age.47, 48
BMI in midlife, which is largely unaffected by underlying disease, may quantify more accurately the effect of adiposity on SCD.49
More than 80% of the women in the US are not current smokers,41
however, the prevalence of other healthful habits is low.41
Among women 45-74 years old in the US, fewer than 40% maintain a BMI <25 kg/m2
, 25% drink light-to-moderate amounts of alcohol and 22% exercise regularly at a light-to-moderate intensity.41
Nationally representative data are not available for the aMed score, but data from NHANES suggest that poor dietary habits are highly prevalent.28
Our data suggest that a substantial portion of SCD risk among nonsmokers was associated with poor diet, lack of exercise and unhealthy weight. Improvement in these lifestyle factors, while ultimately a personal choice, may be facilitated through changes in environmental settings and social norms, in part through public health policies that promote more healthful lifestyle choices.50
There are several limitations to our measure of the PAR% that warrant consideration. First, the PAR% assumes a casual relationship between the low-risk lifestyle factors and risk of SCD. Our study was not randomized, and therefore, this is a large assumption. However, a long-term trial assessing the effects of multiple lifestyle factors on risk of SCD, particularly for primary prevention, has inherent challenges including the necessity of a large sample size and long duration of follow-up and ensuring participant adherence to assigned dietary and exercise prescriptions, for example.51
In lieu of such data, carefully performed observational studies provide a reasonable approach for evaluating the association of multiple lifestyle factors on SCD risk.
Second, to estimate the PAR%, we dichotomized each lifestyle factor, although the relationships between the lifestyle factors and SCD more complex. When we used the expanded risk score, which accounts for the associations across the distribution of the lifestyle factor, the results were similar to the binary lifestyle score. Further, due to its distributive property, the PAR% from a multilevel exposure equals the PAR% calculated from collapsing the categories into a binary variable.39
The simplicity of binary cutpoints for the lifestyle factors mirrors the dichotomous cutpoints used to define low-risk for clinical risk factors, (i.e. total cholesterol <200 mg/dl or blood pressure<120/80) and may help provide discrete guidance for patients in the clinical setting. The set of binary low-risk factors that we utilized here for the prevention of SCD is also similar to an a priori
low-risk lifestyle related to lower risk of CHD15
, CVD mortality21
. A single message for the prevention of CVD and other chronic diseases provides a simple strategy to minimize overall morbidity and premature death.
The PAR% is valid only when the relative risks and prevalence estimates used to calculate the PAR% are unbiased. The high degree of homogeneity in this cohort minimizes confounding by socioeconomic status and potentially other factors associated with a healthy lifestyle.15
We used multivariable models to adjust for additional confounders, however, the potential for residual confounding remains. Although measurement error in self-reported variables is unavoidable, information bias is minimal among these nurses who provide valid information on questionnaires.24, 25
Moreover, such error is likely to be non-differential with respect to SCD, and likely underestimate the true effect.
The PAR% is population-specific, thus the PAR% estimated among mainly Caucasian female health professionals may not be generalizable to men, or to women of other ethnicities. The prevalence of low-risk factors in the NHS is similar to the prevalence among US Caucasian women, but higher than the prevalence among black and Hispanic women.41
Additionally, incidence of SCD is greater, and survival after cardiac arrest is lower, among black Americans.52
Therefore, the impact of a low-risk lifestyle may be greater in more racially diverse populations.
We focused on the influence of modifiable lifestyle habits on SCD. It should be acknowledged that favorable levels of clinical risk factors, such as blood pressure and diabetes, are also associated with lower SCD risk.4
The association between lifestyle factors and SCD is at least partially mediated through these clinical risk factors; however, these later medical conditions are also influenced by factors other than lifestyle. Therefore, we did not include these clinical risk factors in our PAR estimate.
Our study has several important strengths. The repeated assessments of lifestyle factors allow us to update lifestyle habits throughout follow-up. The large number of rigorously confirmed SCDs, which is a difficult phenotype to classify in population studies, is a unique strength. Although we likely missed cases of SCD within this cohort, the high specificity of our defined cases provides a less biased risk estimate.53
Finally, we provide confidence intervals surrounding the PAR%, which are essential for describing estimation uncertainty, but not always presented.54