Bailey, Kent R.

Podocyturia, the shedding of live podocytes, is present at delivery in women with preeclampsia. The aim of this study was to test whether podocyturia is present earlier in pregnancy and predicts for preeclampsia. We also aimed to compare test characteristics of podocyturia with those of angiogenic factors previously implicated in the pathogenesis of this disorder. We prospectively enrolled 315 women who provided blood and urine samples at the end of the second trimesters of their pregnancies (median, 27 gestational weeks) and within 24 hours of their deliveries (median, 39.5 gestational weeks). Blood samples were analyzed for angiogenic markers, including placental growth factor, the soluble receptor fms-like tyrosine kinase receptor-1 for vascular endothelial growth factor, and endoglin. The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours. This analysis included all women who developed preeclampsia (n=15), gestational hypertension (n=15), and a subsample of women who remained normotensive throughout pregnancy (n=44), matched for maternal age and number of previous pregnancies to those who developed preeclampsia. At the second trimester collection, all women who developed preeclampsia had podocyturia, compared with none of those who remained normotensive or were diagnosed with gestational hypertension. Podocyturia in the second trimester had a significantly greater sensitivity and specificity for the subsequent diagnosis of preeclampsia than any single angiogenic marker or a combination thereof. Screening for podocyturia at the end of the second trimester may allow for accurate identification of pregnant women at risk for preeclampsia.

Objectives To provide nursing home ( NH )‐specific estimates to assess whether venous thromboembolism ( VTE ) risk factors identified for the general population apply to NH residents. Design Population‐based case–control study. Setting O lmsted C ounty, M innesota. Participants All county residents with symptomatic objectively diagnosed incident VTE while resident in a NH from 1988 through 2000 (N = 182) and two age‐, sex‐, calendar‐year‐matched non‐ VTE O lmsted C ounty NH residents per case (N = 364). Measurements Provider‐linked medical records were reviewed to obtain information on active malignancy and recent hospitalization, surgery, trauma, or fracture as of index date (case's VTE date; respective provider registration date for controls). Risk factor prevalence and VTE ‐associated odds ratios ( OR ) were estimated and compared with previously obtained data for all O lmsted C ounty residents from 1988 through 2000. For analyses, both groups were limited to individuals aged 65 and older. Results In NH residents, active malignancy, recent hospitalization, and recent surgery significantly increased VTE risk, but the magnitude of risk appeared much lower than general population estimates (e.g., for major surgery, OR = 2.5, 95% confidence interval ( CI ) = 1.4–4.3 for NH residents vs OR = 11, 95% CI = 7.0–17 for general population). In general, the prevalence of all evaluated VTE risk factors appeared much higher in NH controls than in general population controls. Thromboprophylaxis rates appeared higher for NH cases and controls than in the general population; disconcertingly, 47% of NH cases received prophylaxis. Conclusion Although general population VTE risk factors (active cancer and recent hospitalization or surgery) can identify NH residents at higher risk for VTE , these exposures do not adequately stratify VTE risk for thromboprophylaxis recommendations. Further research into NH ‐specific risk factors and prophylaxis effectiveness is required.

Abstract —At the community level, the effect of national programs in increasing hypertension awareness, prevention, treatment, and control is unclear. This study evaluated the degree of detection and control of high blood pressure in a random population-based sample of Olmsted County, Minnesota, residents ≥45 years old, of whom 636 subjects among 1245 eligible residents agreed to participate. Home interview and home and office measurements of blood pressure were used to estimate awareness, treatment, and control rates for hypertension in the community. Mean blood pressures (±SD) were 138/80±20/12 mm Hg for men and 137/76±23/11 mm Hg for women. The overall prevalence of hypertension was 53%. The percentage of subjects with treated and controlled hypertension was 16.6%. Thirty-nine percent of subjects were unaware of their hypertension. Despite clinical trial evidence of reduced morbidity and mortality with antihypertensive therapy, recently reported national data suggest a leveling-off trend for treatment and control of hypertension. This population-based study supports these observations and suggests that at a community level, hypertension awareness and blood pressure control rates are suboptimal, presumably because of decreased attention to the detection and control of hypertension.

Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction <45%), diastolic dysfunction (time constant of left ventricular relaxation >55 milliseconds, left ventricular end-diastolic pressure >18 mm Hg), and left ventricular hypertrophy (left ventricular mass index >120 g/m 2 ) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean+3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m 2 . The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease.

Background —The width of the vena contracta (VC-W), the smallest area of regurgitant flow, reflects the degree of valvular regurgitation and is measurable by color Doppler imaging, but this method has not been validated in aortic regurgitation (AR). Methods and Results —We prospectively examined 79 patients with isolated AR and 80 patients without regurgitation. The VC-W was measured from the long-axis parasternal view and compared with 2 simultaneous reference methods (quantitative Doppler and 2D echocardiography). In patients without regurgitation, the agreement between methods was excellent. In patients with AR, good correlations (all P <0.0001) were obtained between VC-W and effective regurgitant orifice (ERO) area and regurgitant volume recorded by quantitative Doppler ( r =0.89 and 0.90, respectively) and 2D echocardiographic ( r =0.90 and 0.89, respectively) methods. These correlations were similar with eccentric or central jets (all P >0.60). The other methods used showed good correlations of VC-W with aortographic grading of AR (n=8, r =0.82, P =0.01), with the proximal flow convergence method (n=53, r =0.85, P <0.0001), and with left ventricular end-diastolic volume ( r =0.81, P <0.0001). Sensitivity and specificity of VC-W ≥6 mm for diagnosing severe AR (ERO ≥30 mm 2 ) were 95% and 90%, respectively. Conclusions —For assessment of the degree of AR, VC-W shows good correlations with simultaneous quantitative measures (regardless of jet direction), shows good correlations with other methods of assessment of AR, and provides a high diagnostic value for severe AR. VC-W is a simple, reliable method that can be used clinically as part of comprehensive Doppler echocardiographic assessment of AR.

Background —The appropriate management of patients with intermediate-risk Duke treadmill scores is not established. The purpose of this study was to determine the long-term risk of subsequent cardiovascular events in patients with an intermediate-risk treadmill score who do not have myocardial perfusion defects on radionuclide imaging. Methods and Results —The existing databases of the nuclear cardiology laboratories of 4 academic institutions were searched retrospectively. A total of 4649 patients were identified who had intermediate-risk Duke treadmill scores (−10 to 4), normal or near-normal exercise single photon-emission computed tomographic myocardial perfusion images using either thallium-201 or technetium-99m sestamibi, and no previous coronary revascularization. Follow-up was 95% complete. Cardiovascular survival was 99.8% at 1 year, 99.0% at 5 years, and 98.5% at 7 years. Cardiac survival free of myocardial infarction was similarly high at 96.6% at 7 years. Cardiac survival free of myocardial infarction or revascularization was 87.1% at 7 years. Near-normal scans and cardiac enlargement were independent predictors of time to cardiac death. Seven-year cardiac survival was still high at 97.0% in the 357 patients with near-normal scans and normal cardiac size and somewhat lower, at 89.0%, in the 167 patients with cardiac enlargement. Conclusions —Patients with an intermediate-risk treadmill score but with normal or near-normal exercise myocardial perfusion images and normal cardiac sizes are at low risk for subsequent cardiac death and can be safely managed medically until their symptoms warrant revascularization. The appropriate management of patients with cardiac enlargement will remain a matter of clinical judgment.

Background —The prognostic value of treadmill exercise testing (TMET) has been studied in selected populations. The generalizability of these data to different populations and to women is uncertain. Methods and Results —A retrospective, population-based cohort study of all persons (1452 men and 741 women) who underwent TMET in years 1987 to 1989 in Olmsted County, Minnesota, was undertaken. Individuals were followed up for all-cause mortality and cardiac events (cardiac deaths, nonfatal myocardial infarction, or congestive heart failure). Sex-specific analyses were performed to determine whether the predictors of outcome and the magnitude of the associations were similar in both sexes. In men, 77 deaths and 106 cardiac events occurred during 8956 person-years of observation; in women, 46 deaths and 54 cardiac events occurred during 4801 person-years of follow-up. Exercise-induced angina, ECG changes, and workload achieved on the TMET were strongly associated with all-cause mortality and cardiac events in both sexes, and the strength of the association was similar. After adjustment, workload was the only TMET variable associated with outcome. A higher workload was associated with a reduction in the risk of cardiac events and of all-cause mortality; the protective effect of exercise capacity was strong and was similar in both sexes. Conclusions —In this population-based cohort, exercise capacity was the TMET variable that exhibited the strongest association with all-cause mortality and cardiac events. This protective effect of exercise capacity was observed in both sexes.

Background Transesophageal echocardiography (TEE) is the diagnostic modality of choice for visualizing the left atrial appendage (LAA). This study defined the morphology of the LAA in normal autopsy specimen hearts and considered the implications of these findings for TEE studies. Methods and Results Five hundred normal autopsy hearts were reviewed (25 male and 25 female subjects from each decade for 10 decades). LAA length, width, orifice size, and number of lobes were recorded. Number of lobes was compared between sexes with the rank sum test and regressed against age. Mean length, width, and orifice size increased with age, up to age 20 years, in both sexes. Rates were significantly different between sexes for LAA size ( P =.011) and width ( P =.006). After age 20, statistically significant but clinically insignificant age-related changes were observed. Fifty-four percent of LAAs had two lobes (range, 1 to 4), with no age or sex differences. Lobes exist in different planes of the heart. Most pectinate muscles were ≥1 mm in width. Pectinate muscles <1 mm (2.6% of cases) were seen in only the first and last decades. Conclusions Age- and sex-related differences in LAA dimensions exist. These differences and the existence of multilobed appendages are important in the accurate TEE evaluation of LAA. Because lobes exist in different planes, imaging must be done in multiple planes to visualize the entire LAA.