Identification of subjects
During the six year period from Feb 1st 2002 to Jan 31st 2008, 1404 adult cases of SCD (age ≥ 18) were identified in the Portland, Oregon metropolitan area that had medical records available for analysis. Of these, 619 (44%) had documented CAD. Among case subjects with documented CAD, 193 (31%) had echocardiograms and met inclusion criteria. For the same time period, 528 adult control subjects with CAD were enrolled. All controls had medical records available, and 203 (38%) had echocardiograms. After exclusion of two cases with hypertrophic cardiomyopathy, 191 cases and 203 controls remained for the analysis.
Timing of echocardiogram relative to time of arrest or ascertainment
All included case subjects had an echocardiogram prior to arrest, with 76% within two years of arrest, and 24% more than two years prior (range 2.1 – 9.7 years prior). Over half (59%) of control subjects had echocardiograms prior to ascertainment (46% within two years and 13% more than two years prior (range 2.1 – 6.5 years prior), 14% had their echocardiogram performed on the day of ascertainment, and 27% up to 5 days post-ascertainment. There were no differences in mean LV mass or prevalence of LVH for control subjects with peri- or post-ascertainment echocardiograms vs. those subjects with echocardiograms performed prior to ascertainment (p≥0.59).
Clinical characteristics of cases and controls
Case subjects were slightly older than control subjects (72 vs. 67 years, p=0.0002), but did not differ by gender, mean BMI, or prevalence of hypertension (p≥0.08) (). Diabetes and a history of atrial fibrillation or flutter were more common in cases (p≤0.003) (). Case subjects also had higher serum creatinine levels (p<0.0001), but cholesterol levels did not differ (p=0.17). Case subjects were slightly more likely to be taking beta blockers and ACE inhibitors, and slightly less likely to be taking angiotensin receptor blockers, but these differences did not reach significance (p≥0.08) (). Over one-half of control subject vs. one-quarter of case subjects had normal LVSD; mild-to-moderate and severe LVSD were more common in cases vs. controls (p<0.0001).
Demographic and clinical characteristics of 191 cases and 203 controls with coronary disease
Prevalence of LVH and increased LV mass in cases and controls
Case patients were more likely to have LVH than control patients (48% vs. 25%, p<0.0001) (). When subjects were stratified by presence of severe LVSD, this difference was also observed in patients without LVSD (42% in cases vs. 21% in controls, p<0.0001). While the overall prevalence of LVH was higher in patients with LVSD, case-control differences were attenuated (58% in cases vs. 42% in controls, p=0.10) (). illustrates that LVH was more common among cases in each category of LV function.
Distribution of LV hypertrophy and LV mass in 191 cases and 203 controls with coronary disease
Frequency of LV hypertrophy (LVH, by measurement of echocardiographic LV mass) among LV function sub-groups in cases and controls. A greater prevalence of LVH was observed in case subjects, across all categories of LV systolic function.
Mean adjusted LV mass was also significantly greater among SCD cases than among control subjects (129 g/m2 vs. 107 g/m2, p<0.0001) (), with the distribution of adjusted LV mass shifted toward higher values in the case group (). These differences were observed in both men (136 g/m2 vs. 110 g/m2, p<0.0001) and women (113 g/m2 vs. 100 g/m2, p = 0.05; data not shown). Mean adjusted LV mass was greater in cases than controls in both the presence and absence of severe LVSD ().
Distribution of LV mass (normalized for body surface area) in cases and controls shows a rightward shift toward higher values in the case group.
The severity of LVH appeared worse among cases as well; cases were much more likely than controls to have LV mass ≥ 25% above the LVH cut-off (p<0.0001, ). When the joint distribution of severe LVSD and LVH were examined, patients with combined severe LVSD and LVH were significantly more likely to be found in the case group compared to the control group (28% vs. 8%), as were subjects who had LVH alone (27% vs. 17%) (p<0.0001) (, ).
Distribution of severe LV systolic dysfunction (LVSD) and LV hypertrophy (LVH) in cases vs. controls. Case subjects were more likely than control subjects to have co-existing severe LVSD and LVH.
Severe LVSD and LVH independently increase odds of SCD
In the logistic regression model evaluating the relationship between SCD and LVSD and including all terms significant at p<0.10 in univariate analyses, BMI, use of beta blockers, and gender were removed from the final model because they were not significant in the multivariate model (p≥0.36). Controlling for age, diabetes, serum creatinine level, history of atrial fibrillation/flutter, and a history of medication with angiotensin receptor blockers, severe LVSD doubled the odds of SCD (OR 2.1, 95% CI 1.3 – 3.5). When LVH was added to the full multivariate model with all terms significant at p<0.10 in , there was no significant interaction between LVSD and LVH (p=0.74). As in the previous model, BMI, use of beta-blockers, and gender were non-significant (p≥0.25) and were removed. In the final model controlling for all remaining covariates, both severe LVSD and LVH independently nearly doubled the odds of SCD (OR 1.9, 95% CI 1.1 – 3.2 for severe LVSD; and OR 1.8, 95% CI 1.1 – 2.9 for LVH) ().
Multivariate odds ratio estimates for sudden cardiac death (SCD) associated with severe LVSD and LVH.
Joint effects of LVSD and LVH
When severe LVSD and LVH were considered in a logistic model that estimated lone effects and joint effects separately, subjects with both LVH and severe LVSD had a much higher odds of SCD compared to subjects with neither condition (OR 3.5, 95% CI 1.7 – 7.2), indicating that the presence of both conditions additively increases the odds of SCD.