Bailey, Kent R.

Background— Limited data exist on trends in incidence of atrial fibrillation (AF). We assessed the community-based trends in AF incidence for 1980 to 2000 and provided prevalence projections to 2050. Methods and Results— The adult residents of Olmsted County, Minnesota, who had ECG-confirmed first AF in the period 1980 to 2000 (n=4618) were identified. Trends in age-adjusted incidence were determined and used to construct model-based prevalence estimates. The age- and sex-adjusted incidence of AF per 1000 person-years was 3.04 (95% CI, 2.78 to 3.31) in 1980 and 3.68 (95% CI, 3.42 to 3.95) in 2000. According to Poisson regression with adjustment for age and sex, incidence of AF increased significantly ( P =0.014), with a relative increase of 12.6% (95% CI, 2.1 to 23.1) over 21 years. The increase in age-adjusted AF incidence did not differ between men and women ( P =0.84). According to the US population projections by the US Census Bureau, the number of persons with AF is projected to be 12.1 million by 2050, assuming no further increase in age-adjusted incidence of AF, but 15.9 million if the increase in incidence continues. Conclusions— The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000. Whether or not this rate of increase continues, the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.

OBJECTIVE—The aim of the present study was to assess the diagnostic accuracy of the Adult Treatment Panel III (ATP-III) definition of the metabolic syndrome in identifying insulin-resistant individuals and to explore alternative approaches to improve identification of insulin-resistant individuals among asymptomatic adults from the general population. RESEARCH DESIGN AND METHODS—The sample consisted of 256 non-Hispanic white subjects without treated hypertension or diabetes, from the Rochester (Minnesota) Heart Family Study (123 men and 133 women; aged 20–60 years). Frequently sampled intravenous glucose tolerance tests were performed in all subjects. The reference standard for insulin resistance was determined by Bergman’s minimal model; insulin resistance was defined as an insulin sensitivity index <2 × 10 min−1 · μU−1 · ml−1. Component metabolic syndrome measures included blood pressure determined by sphygmomanometer; fasting serum triglycerides, HDL cholesterol, and glucose concentrations determined enzymatically; and waist circumference determined by tape measure. RESULTS—By ATP-III criteria, the prevalence of metabolic syndrome was 15.6% (16.3% in men and 15.1% in women; P = 0.465). The presence of metabolic syndrome had low sensitivity to identify insulin resistance (45% in men and 39% in women; sex difference, P = 0.137) but high specificity (93% in men and 95% in women; sex difference, P = 0.345). Based on the area under the receiver operating characteristic curve (AUC) constructed by counting metabolic syndrome components as recommended by ATP-III, diagnostic accuracy was fair (AUC = 0.797 in men and 0.747 in women). When component metabolic syndrome measures were considered as quantitative traits rather than dichotomized, use of waist circumference alone, rather than counting metabolic syndrome components, improved diagnostic accuracy for insulin resistance (in men, AUC = 0.906, P = 0.001; in women, AUC = 0.822, P = 0.10). CONCLUSIONS—Application of the ATP-III metabolic syndrome criteria provides good specificity but low sensitivity to screen asymptomatic white adults for insulin resistance. Measuring just waist circumference is simpler and may provide greater accuracy for identifying insulin resistance.

Background and Purpose— In the present study, the effect of subarachnoid hemorrhage (SAH) on the phosphorylation of endothelial NO synthase (eNOS) and the ability of recombinant erythropoietin (Epo) to augment this vasodilator mechanism in the spastic arteries were studied. Methods— Recombinant adenoviral vectors (10 9 plaque-forming units per animal) encoding genes for human Epo (AdEpo), and β-galactosidase were injected immediately after injection of autologous arterial blood into the cisterna magna (day 0) of rabbits. Cerebral angiography was performed on day 0 and day 2, and basilar arteries were harvested for Western blots, measurement of cGMP levels, and analysis of vasomotor functions. Results— Injection of autologous arterial blood into cisterna magna resulted in significant vasospasm of the basilar arteries. Despite the narrowing of arterial diameter and reduced expression of eNOS, expressions of phosphorylated protein kinase B (Akt) and phosphorylated eNOS were significantly increased in spastic arteries. Gene transfer of AdEpo reversed the vasospasm. AdEpo-transduced basilar arteries demonstrated significant augmentation of the endothelium-dependent relaxations to acetylcholine, whereas the relaxations to an NO donor, 2-( N , N -diethylamino)diazenolate-2-oxide sodium salt, were not affected. Transduction with AdEpo further increased the expression of phosphorylated Akt and eNOS and elevated basal levels of cGMP in the spastic arteries. Conclusions— Phosphorylation of eNOS appears to be an adaptive mechanism activated during development of vasospasm. The vascular protective effect of Epo against cerebral vasospasm induced by SAH may be mediated in part by phosphorylation of Akt/eNOS.

Background and Purpose— With the changes in management of atrial fibrillation (AF) over time, it is possible that the time trends of post-AF stroke incidence and mortality have changed. We sought to determine whether the incidence and survival of ischemic stroke after AF diagnosis have improved. Methods— We identified the Olmsted County, Minn, residents who developed first AF from 1980 to 2000 and followed them in medical records to 2004. The outcomes were first ischemic stroke and death. Results— Of the 4117 subjects diagnosed with first AF and without previous stroke, 446 (11%) sustained a first ischemic stroke during a mean follow-up time of 5.5±5.0 years. The age- and sex-adjusted incidence of stroke decreased, on average, by 3.4% per year ( P =0.0001), concurrent with an increase in warfarin and aspirin use (both P <0.0001) and reduction of systolic blood pressure ( P <0.001). The age-adjusted ischemic stroke incidence was higher in women ( P =0.039), but not after adjusting for systolic blood pressure ( P =0.41). Compared with the general Minnesota white population, the relative mortality hazard ratio was 1.88 for men and 1.84 for women without stroke and 3.03 for men and 3.80 for women ( P <0.05) with stroke. The relative mortality hazard did not vary by age or calendar year of AF diagnosis. Conclusions— Post-AF ischemic stroke incidence decreased significantly from 1980 to 2000, during which time a substantial increase in the use of antithrombotic therapy and reduction of systolic blood pressure was evident. The relative mortality risk of stroke, however, had not improved over time.

Background— Sinus venosus atrial septal defect (SVASD) differs from secundum atrial septal defect by its atrial septal location and its association with anomalous pulmonary venous connection (APVC). Data on long-term outcome after surgical repair are limited. Methods and Results— We reviewed outcomes of 115 patients (mean age±SD 34±23 years) with SVASD who had repair from 1972 through 1996. APVC was present in 112 patients (97%). Early mortality was 0.9%. Complete follow-up was obtained for 108 patients (95%) at 144±99 months. Symptomatic improvement was noted in 83 patients (77%), and deterioration was noted in 17 patients (16%). At follow-up, 7 (6%) of 108 patients had sinus node dysfunction, a permanent pacemaker, or both, and 15 (14%) of 108 patients had atrial fibrillation. Older age at repair was predictive of postoperative atrial fibrillation ( P =0.033). No reoperations were required during follow-up. Survival was not different from expected for an age- and sex-matched population. Clinical improvement was more common with older age at surgery ( P =0.014). Older age at repair ( P =0.008) and preoperative New York Heart Association class III or IV ( P =0.038) were independent predictors of late mortality. Conclusions— Operation for SVASD is associated with low morbidity and mortality, and postoperative subjective clinical improvement occurs irrespective of age at surgery. Postoperative atrial fibrillation appears to be related to older age at operation. SVASD repair achieves survival similar to that of a matched population and should be considered whenever repair may impact survival or symptoms.

Background— This study assessed the long-term outcome of a large, asymptomatic population with hemodynamically significant aortic stenosis (AS). Methods and Results— We identified 622 patients with isolated, asymptomatic AS and peak systolic velocity ≥4 m/s by Doppler echocardiography who did not undergo surgery at the initial evaluation and obtained follow-up (5.4±4.0 years) in all. Mean age (±SD) was 72±11 years; there were 384 (62%) men. The probability of remaining free of cardiac symptoms while unoperated was 82%, 67%, and 33% at 1, 2, and 5 years, respectively. Aortic valve area and left ventricular hypertrophy predicted symptom development. During follow-up, 352 (57%) patients were referred for aortic valve surgery and 265 (43%) patients died, including cardiac death in 117 (19%). The 1-, 2-, and 5-year probabilities of remaining free of surgery or cardiac death were 80%, 63%, and 25%, respectively. Multivariate predictors of all-cause mortality were age (hazard ratio [HR], 1.05; P <0.0001), chronic renal failure (HR, 2.41; P =0.004), inactivity (HR, 2.00; P =0.001), and aortic valve velocity (HR, 1.46; P =0.03). Sudden death without preceding symptoms occurred in 11 (4.1%) of 270 unoperated patients. Patients with peak velocity ≥4.5 m/s had a higher likelihood of developing symptoms (relative risk, 1.34) or having surgery or cardiac death (relative risk, 1.48). Conclusions— Most patients with asymptomatic, hemodynamically significant AS will develop symptoms within 5 years. Sudden death occurs in ≈1%/y. Age, chronic renal failure, inactivity, and aortic valve velocity are independently predictive of all-cause mortality.

Markers of inflammation are predictive of cardiovascular events but their association with atherosclerotic burden remains poorly defined. We hypothesized that markers of inflammation, including C-reactive protein (CRP), white blood cell (WBC) count, and lipoprotein-associated phospholipase A2 (Lp-PLA2), would be associated with the ankle-brachial index (ABI), a marker of atherosclerotic burden. Subjects were 247 patients referred for lower extremity arterial evaluation to the non-invasive vascular laboratory excluding those with active infection or lower extremity revascularization within the previous year. ABI was measured at two sites in both legs and the lowest of four measurements was used in the analyses. CRP was measured by a high-sensitivity immunoturbidimetric assay and Lp-PLA2 was measured by ELISA. The mean patient age was 68±11 years, and 54% were men. Mean ABI was 0.84-0.31 and 49% had an ABI < 0.9. Age, hypertension, fasting plasma glucose, and ‘ever’ smoking were independently associated with the ABI. Spearman correlation coefficients of inflammatory markers with the ABI were: CRP (r 1/4-0.15, p 1/4-0.02), WBC count (r 1/4-0.27, p 1/4-0.001), and Lp-PLA2 (r 1/4-0.09, p 1/4-0.21). In a multiple regression model that included conventional risk factors and statin use, CRP and WBC count were no longer significantly associated with ABI, whereas Lp-PLA2 was a borderline-significant predictor of lower ABI (p 1/4-0.05). These data indicate that CRP and WBC count are not independently associated with ABI, a marker of atherosclerotic burden in subjects referred for non-invasive lower extremity arterial evaluation. The association of Lp-PLA2 with ABI merits further study.

Background— Preclinical systolic or diastolic dysfunction is associated with increased morbidity and mortality. We postulated that plasma brain natriuretic peptide (BNP) might serve as a biomarker for preclinical ventricular dysfunction (PCVD) but that the discriminatory values for BNP may vary with age and sex. Methods and Results— We measured BNP, systolic and diastolic ventricular function, and clinical parameters in 2042 randomly selected residents of Olmsted County, Minn, aged 45 years or older. For preclinical systolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with more severe (0.82 to 0.92) than any (0.51 to 0.74) systolic dysfunction and were similar in men and women and in younger and older persons. For preclinical diastolic dysfunction, the areas under the receiver operating characteristics curve were higher for those with moderate-to-severe (0.74 to 0.79) than any (0.52 to 0.68) diastolic dysfunction and were similar regardless of age or sex. Optimal discriminatory values of BNP varied with age and sex. Considering the prevalence of preclinical systolic or diastolic dysfunction and the predictive characteristics observed, using BNP to screen for PCVD would necessitate echo in 10% to 40% of those screened, with most confirmatory echocardiograms being negative, and would miss 10% to 60% of those affected. Conclusions— BNP is a suboptimal screening test for PCVD in the population.

Few studies have investigated whether ethnic groups differ in the prevalence of peripheral arterial disease (PAD). We compared the distribution of the ankle-brachial index (ABI), a measure of PAD, between African Americans and non-Hispanic white individuals. Subjects (n = 931) belonged to the Genetic Epidemiology Network of Arteriopathy (GENOA) study, a community-based study of hypertensive sibships, and included 453 African Americans from Jackson, Mississipi (mean age 72 6 years, 69% women) and 478 non-Hispanic white individuals from Rochester, Minnesota (mean age 58 7 years, 64% women). ABI was determined at two sites in each lower extremity and the lowest of four indices was used in the analyses. PAD was defined as an ABI of 0.95. Information about conventional risk factors was derived from interviews and from blood samples drawn at the study visit. The prevalence of diabetes and hypertension was significantly higher in African Americans than in non-Hispanic white individuals. After adjusting for age, African American subjects had a lower mean ABI (women 0.97 vs 1.04, p < 0.001; men 0.96 vs 1.12, p < 0.001) and a greater prevalence of PAD (women 34% vs 22%, p = 0.010; men 33% vs 11%, p < 0.001) than their non-Hispanic white counterparts. In multiple regression analyses, African American ethnicity was a predictor of a lower ABI and the presence of PAD in each sex after adjusting for age and other conventional risk factors. In conclusion, the lower ABI and greater prevalence of PAD in African Americans than in non-Hispanic white individuals is not explained by differences in conventional risk factors. Identifying additional ‘novel’ risk factors that account for the ethnic differences in PAD is an important next step towards understanding why such differences exist and developing more effective strategies to reduce the burden of PAD.