Todd A. Schwartz

Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension

OBJECTIVES The aim of this study was to evaluate the relationships between echocardiographic findings and clinical outcomes in patients with severe primary pulmonary hypertension (PPH). BACKGROUND Primary pulmonary hypertension is associated with abnormalities of right heart structure and function that contribute to the poor prognosis of the disease. Echocardiographic abnormalities associated with PPH have been described, but the prognostic significance of these findings remains poorly characterized. METHODS Echocardiographic studies, invasive hemodynamic measurements and 6-min walk tests were performed and outcomes prospectively followed in 81 patients with severe PPH. Subjects were participants in a 12-week randomized trial examining the effects of prostacyclin plus conventional therapy compared with conventional therapy alone. RESULTS During the mean follow-up period of 36.9 +/- 15.4 months, 20 patients died and 21 patients underwent transplantation. Pericardial effusion (p = 0.003) and indexed right atrial area (p = 0.005) were predictors of mortality. Pericardial effusion (p = 0.017), indexed right atrial area (p = 0.012) and the degree of septal shift in diastole (p = 0.004) were predictors of a composite end point of death or transplantation. In multivariable analyses incorporating clinical, hemodynamic and echocardiographic variables, pericardial effusion and an enlarged right atrium remained predictors of adverse outcomes. Six-minute walk results, mixed venous oxygen saturation and initial treatment randomization were also independently associated with a poor prognosis. CONCLUSIONS Pericardial effusion, right atrial enlargement and septal displacement are echocardiographic abnormalities that reflect the severity of right heart failure and predict adverse outcomes in patients with severe PPH. These characteristics may help identify patients appropriate for more intensive medical therapy or earlier transplantation.

Lifetime risk of symptomatic knee osteoarthritis

OBJECTIVE To estimate the lifetime risk of symptomatic knee osteoarthritis (OA), overall and stratified by sex, race, education, history of knee injury, and body mass index (BMI). METHODS The lifetime risk of symptomatic OA in at least 1 knee was estimated from logistic regression models with generalized estimating equations among 3,068 participants of the Johnston County Osteoarthritis Project, a longitudinal study of black and white women and men age >or=45 years living in rural North Carolina. Radiographic, sociodemographic, and symptomatic knee data measured at baseline (1990-1997) and first followup (1999-2003) were analyzed. RESULTS The lifetime risk of symptomatic knee OA was 44.7% (95% confidence interval [95% CI] 40.0-49.3%). Cohort members with history of a knee injury had a lifetime risk of 56.8% (95% CI 48.4-65.2%). Lifetime risk rose with increasing BMI, with a risk of 2 in 3 among those who were obese. CONCLUSION Nearly half of the adults in Johnston County will develop symptomatic knee OA by age 85 years, with lifetime risk highest among obese persons. These current high risks in Johnston County may suggest similar risks in the general US population, especially given the increase in 2 major risk factors for knee OA, aging, and obesity. This underscores the immediate need for greater use of clinical and public health interventions, especially those that address weight loss and self-management, to reduce the impact of having knee OA.

Prevalence of Hip Symptoms and Radiographic and Symptomatic Hip Osteoarthritis in African Americans and Caucasians: The Johnston County Osteoarthritis Project

Objective. To report contemporary estimates of the prevalence of hip-related osteoarthritis (OA) outcomes in African Americans and Caucasians aged ≥ 45 years. Methods. Weighted prevalence estimates and their corresponding 95% confidence intervals for hip symptoms, radiographic hip OA, symptomatic hip OA, and severe radiographic hip OA were calculated using SUDAAN® for age, race, and sex subgroups among 3068 participants (33% African Americans, 38% men) in the baseline examination (1991–97) of The Johnston County Osteoarthritis Project, a population-based study of OA in North Carolina. Radiographic hip OA was defined as Kellgren-Lawrence radiographic grade ≥ 2, moderate/severe radiographic hip OA as grades 3 and 4, and symptomatic hip OA as hip symptoms in a hip with radiographic OA. Results. Hip symptoms were present in 36%; 28% had radiographic hip OA; nearly 10% had symptomatic hip OA; and 2.5% had moderate/severe radiographic hip OA. Prevalence of all 4 outcomes was higher in older individuals; most outcomes were higher for women and African Americans. Conclusion. African Americans in this population do not have a lower prevalence of hip-related OA outcomes as previous studies suggested. Increasing public and health system awareness of the relatively high prevalence of these outcomes, which can be disabling, may help to decrease their effects and ultimately prevent them.

Gender Differences in Survival in Advanced Heart Failure Insights From the FIRST Study

BACKGROUND Previous natural history studies in broad populations of heart failure patients have associated female gender with improved survival, particularly in patients with a nonischemic etiology of ventricular dysfunction. This study investigates whether a similar survival advantage for women would be evident among patients with advanced heart failure. METHODS AND RESULTS The study analysis is based on the Flolan International Randomized Survival Trial (FIRST) study which enrolled 471 patients (359 men and 112 women) who had evidence of end-stage heart failure with marked symptoms (60% NYHA class IV) and severe left ventricular dysfunction (left ventricular ejection fraction 18+/-4.9%). A Cox proportional-hazards model, adjusted for age, gender, 6-minute walk, dobutamine use at randomization, mean pulmonary artery blood pressure, and treatment assignment, showed a significant association between female gender and better survival (relative risk of death for men versus women was 2.18, 95% CI 1.39 to 3.41; P<0.001). Although formal interaction testing was negative (P=0.275), among patients with a nonischemic etiology of heart failure, the relative risk of death for men versus women was 3.08 (95% CI 1.56 to 6.09, P=0.001), whereas among those with ischemic heart disease, the relative risk of death for men versus women was 1.64 (95% CI 0.87 to 3.09, P=0.127). CONCLUSIONS Women with advanced heart failure appear to have better survival than men. Subgroup analysis suggests this finding is strongest among patients with a nonischemic etiology of heart failure.

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

BACKGROUND Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. METHODS AND RESULTS Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. CONCLUSIONS Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system.

Depressive symptoms in mothers of prematurely born infants

Objective: This longitudinal, descriptive study described the level of depressive symptoms in mothers of preterm infants from birth through 27 months corrected age and examined factors associated with depressive symptoms. The framework for the study was guided by an ecological developmental systems perspective and an adaptation of the Preterm Parental Distress Model. Methods: In this model, we hypothesize that a mothers emotional distress to the birth and parenting of a prematurely born child is influenced by personal and family factors, severity of the infants health status, and illness-related stress and worry. Participants were 102 mothers of preterm infants who were off the ventilator and not otherwise dependent on major technology at enrollment. Results: Mean depressive symptoms scores on the Center for Epidemiologic Studies Depression Scale (CES-D) during hospitalization were high and more than half the mothers (63%) had scores of ≥16 indicating risk of depression. Depressive scores declined over time until 6 months and then were fairly stable. Unmarried mothers, mothers of infants who were rehospitalized, and mothers who reported more maternal role alteration stress during hospitalization and worry about the childs health had more depressive symptoms through the first year. Mothers who reported more parental role alteration stress during hospitalization (odds ratio [OR] = 1.570, 95% confidence interval [CI]: 1.171–2.104) and more worry about the childs health (OR = 2.350, 95% CI: 1.842–2.998) were more likely to experience elevated CES-D scores that put them at risk of depression. Also, mothers of rehospitalized infants had decreasing odds of elevated CES-D scores over time (OR = 0.982 per week, 95% CI: 0.968–0.996). Conclusions: Findings have implications for the support of mothers during hospitalization and in the early years of parenting a preterm infant.

Clinical benefits of low serum digoxin concentrations in heart failure

OBJECTIVES We sought to determine whether there was a relationship between serum digoxin concentration (SDC), including SDCs typically regarded as low, and clinical efficacy related to digoxin in patients with symptomatic left ventricular dysfunction. BACKGROUND Digitalis glycosides have been used for 200 years in the treatment of heart failure (HF), but the SDC required for optimal clinical efficacy and acceptable toxicity remains controversial. METHODS This relationship was investigated by utilizing data from two randomized, double-blinded, placebo-controlled, digoxin-withdrawal trials: the Prospective Randomized study Of Ventricular failure and Efficacy of Digoxin (PROVED) and the Randomized Assessment of Digoxin on Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Major end points were worsening HF, change in left ventricular ejection fraction and treadmill time after randomization. The primary analysis investigated the relationship between SDC at randomization and these end points. A secondary categorical analysis compared these end points in patients who discontinued digoxin versus patients who continued digoxin and had low (0.5 to 0.9 ng/ml), moderate (0.9 to 1.2 ng/ml) or high (>1.2 ng/ml) SDCs at randomization. RESULTS Multiple regression analysis failed to find a relationship between randomization SDC, considered as a continuous variable, and any study end point (all p > 0.236). Multivariable Cox analysis found that the risk of worsening HF was significantly less (all p < 0.02) for patients in any category of SDC who continued digoxin, as compared with patients withdrawn from digoxin. Specifically, patients in the low SDC category were significantly less likely than placebo patients to experience worsening HF during follow-up (p = 0.018). CONCLUSIONS The beneficial effects of digoxin on common clinical end points in patients with HF were similar, regardless of SDC.

One in four people may develop symptomatic hip osteoarthritis in his or her lifetime

OBJECTIVE To estimate the lifetime risk of symptomatic hip osteoarthritis (OA). DESIGN We analyzed data from the Johnston County Osteoarthritis Project [a longitudinal population-based study of OA in North Carolina, United States (n=3068)]. The weighted baseline sample comprised 18% blacks and 54% women, and the mean age was 63 years (range=45-93). Symptomatic hip OA was defined as a Kellgren-Lawrence (K-L) radiographic score of ≥ 2 (anterior-posterior pelvis X-rays) and pain, aching or stiffness on most days, or groin pain, in the same hip. Lifetime risk, defined as the proportion who developed symptomatic hip OA in at least one hip by age 85, among people who live to age 85, was modeled using logistic regression with repeated measures (through generalized estimating equations). RESULTS Lifetime risk of symptomatic hip OA was 25.3% [95% confidence interval (CI)=21.3-29.3]. Lifetime risk was similar by sex, race, highest educational attainment, and hip injury history. We studied lifetime risk by body mass index (BMI) in three forms: at age 18; at baseline and follow-up; and at age 18, baseline and follow-up and found no differences in estimates. CONCLUSION The burden of symptomatic hip OA is substantial with one in four people developing this condition by age 85. The similar race-specific estimates suggest that racial disparities in total hip replacements are not attributable to differences in disease occurrence. Despite increasing evidence that obesity predicts an increased risk of both hip OA and joint replacement, we found no association between BMI and lifetime risk.

A randomized controlled trial of the people with arthritis can exercise program: Symptoms, function, physical activity, and psychosocial outcomes

OBJECTIVE To evaluate the basic 8-week People with Arthritis Can Exercise (PACE) program for improvements in primary (symptoms, functioning, level of physical activity) and secondary (psychosocial) outcomes. METHODS A total of 346 individuals with self-reported arthritis from 18 sites participated in a randomized controlled trial of PACE. Outcomes were measured at baseline and 8 weeks. The intervention group completed self-reported assessments at 3 and 6 months. Two-level multiple linear regression models were estimated to calculate adjusted outcome means in the intervention and control groups. A mixed-effects repeated-measures model was used to calculate adjusted means in the intervention group at 3 and 6 months. Both intent-to-treat (ITT) and as-treated (AT) analyses were conducted. RESULTS At 8 weeks, the intervention group had improvements in the following outcomes: 2 symptom outcomes (pain, fatigue) and 1 psychosocial outcome (self-efficacy for managing arthritis) in the ITT analyses; 1 symptom outcome (pain), 1 function outcome (chair stands), and 1 psychosocial outcome (self-efficacy for arthritis management) in the AT analyses. In addition, completers who attended>or=9 classes had improvements in 3 symptom outcomes (pain, fatigue, stiffness), 2 function outcomes (10-pound lifts, chair stands), and 1 psychosocial outcome (self-efficacy for arthritis management) at 8 weeks. Relative to baseline, PACE participants maintained significant improvements in symptoms at 6 months, but declined in function and self-efficacy for exercise. CONCLUSION If adults with arthritis attend a majority of PACE classes, they may expect improvements in symptoms, self-efficacy for arthritis management, and upper and lower extremity function. Achieving sustained improvement in outcomes may require continued participation in PACE.

Anthropometric measures, body composition, body fat distribution, and knee osteoarthritis in women

Objective: Increased BMI is a well‐recognized risk factor for radiographic knee osteoarthritis (rKOA); however, the contributions of the components of body composition, body fat distribution, and height to this association are not clear.