Faculty Bibliography

Although most mental disorders have their first onset by young adulthood, there are few longitudinal studies of these problems and related help-seeking behavior. The present study examined some early and current predictors of the use of mental health services among African-American and Puerto Rican participants in their mid-30s. The 674 participants (52.8 % African Americans, 47.2 % Puerto Ricans; 60.1 % women) in this study were first seen in 1990 when the participants attended schools serving the East Harlem area of New York City. A structural equation model controlling for the participants' gender, educational level in emerging adulthood, and age at the most recent data collection showed significant standardized pathways from both ethnicity (beta = -0.28; z = -4.82; p < 0.001) and psychological symptoms (beta = 0.15; z = 2.41; p < 0.05), both measured in emerging adulthood, to smoking in the early 30s. That, in turn, was associated with certain physical diseases and symptoms (i.e., respiratory) in the mid-30s (beta = 0.16; z = 2.59; p < 0.05). These physical diseases and symptoms had a cross-sectional association with family financial difficulty in the mid-30s (beta = 0.21; z = 4.53; p < 0.001), which in turn also had a cross-sectional association with psychiatric disorders (beta = 0.30; z = 5.30; p < 0.001). Psychiatric disorders had a cross-sectional association with mental health services utilization (beta = 0.65; z = 13.25; p < 0.001). Additional pathways from the other domains to mental health services utilization in the mid-30s were also supported by the mediating role of psychiatric disorders. Results obtained from this research offer theoretical and practical information regarding the processes leading to the use of mental health services.

: Optical coherence tomography (OCT) has made possible the structure-function correlations that uniquely characterize the afferent visual pathway as a model for understanding multiple sclerosis (MS) and for developing new treatments. During the past decade, OCT measures of retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCL + IPL) thickness have evolved from being a means to validate visual function tests, such as low-contrast letter acuity, to provide a window on the axonal and neuronal loss that are now widely recognized as contributors to permanent visual dysfunction in MS. Although acute optic neuritis (ON) leads to thinning of the RNFL by 20%-40% within 3 months after a single episode, thinning of the RNFL and GCL + IPL occur over time in MS eyes even in the absence of an acute ON history. As such, OCT and its functional and patient-reported correlates of low-contrast acuity and vision-specific quality of life (QOL) have now been incorporated into MS clinical trials. Results of an ongoing, phase 2 trial of a remyelinating agent that uses acute ON as a model for assessing therapeutic efficacy will define even further the important role for OCT in documenting structural changes as we move forward from clinical trials to clinical use.

OBJECTIVES: This study tested whether myocardial extracellular volume (ECV) is increased in patients with hypertension and atrial fibrillation (AF) undergoing pulmonary vein isolation and whether there is an association between ECV and post-procedural recurrence of AF. BACKGROUND: Hypertension is associated with myocardial fibrosis, an increase in ECV, and AF. Data linking these findings are limited. T1 measurements pre-contrast and post-contrast in a cardiac magnetic resonance (CMR) study provide a method for quantification of ECV. METHODS: Consecutive patients with hypertension and recurrent AF referred for pulmonary vein isolation underwent a contrast CMR study with measurement of ECV and were followed up prospectively for a median of 18 months. The endpoint of interest was late recurrence of AF. RESULTS: Patients had elevated left ventricular (LV) volumes, LV mass, left atrial volumes, and increased ECV (patients with AF, 0.34 +/- 0.03; healthy control patients, 0.29 +/- 0.03; p < 0.001). There were positive associations between ECV and left atrial volume (r = 0.46, p < 0.01) and LV mass and a negative association between ECV and diastolic function (early mitral annular relaxation [E'], r = -0.55, p < 0.001). In the best overall multivariable model, ECV was the strongest predictor of the primary outcome of recurrent AF (hazard ratio: 1.29; 95% confidence interval: 1.15 to 1.44; p < 0.0001) and the secondary composite outcome of recurrent AF, heart failure admission, and death (hazard ratio: 1.35; 95% confidence interval: 1.21 to 1.51; p < 0.0001). Each 10% increase in ECV was associated with a 29% increased risk of recurrent AF. CONCLUSIONS: In patients with AF and hypertension, expansion of ECV is associated with diastolic function and left atrial remodeling and is a strong independent predictor of recurrent AF post-pulmonary vein isolation.

BACKGROUND: Although pulmonary vein isolation has become a mainstream therapy for selected patients with atrial fibrillation (AF), late recurrent AF is common and its risk factors remain poorly defined. The purpose of our study was to test the hypothesis that reduced left atrial passive emptying function (LAPEF) as determined by cardiac magnetic resonance has a strong association with late recurrent AF after pulmonary vein isolation. METHODS AND RESULTS: Three hundred forty-six patients with AF referred for cardiac magnetic resonance pulmonary vein mapping before pulmonary vein isolation were included. Maximum LA volumes (VOLmax) and volumes before atrial contraction (VOLbac) were measured; LAPEF was calculated as (VOLmax-VOLbac)/VOLmaxx100. Kaplan-Meier curves were constructed to determine late recurrent AF stratified by LAPEF quintile. Cox proportional hazards regression was used to adjust for known markers of recurrence. During a median follow-up of 27 months, 124 patients (35.8%) experienced late recurrent AF. Patients with recurrence were more likely to have nonparoxysmal AF (75.8% versus 51.4%; P<0.01), higher mean VOLmax (60.2 versus 52.8 mL/m(2); P<0.01), and lower mean LAPEF (19.1% versus 26.0%; P<0.01). Patients in the lowest LAPEF quintile were at highest risk of developing recurrent AF (2-year recurrence for lowest versus highest: 60.5% versus 17.3%; P<0.01). After adjusting for known predictors of recurrence, patients with low LAPEF remained significantly more likely to recur (hazard ratio for lowest versus highest quintile, 3.92; 95% confidence interval, 2.01-7.65). CONCLUSIONS: We found a strong association between LAPEF and recurrent AF after pulmonary vein isolation that persisted after multivariable adjustment.

CONTEXT: In older adults with multiple conditions, medications may not impart the same benefits seen in patients who are younger or without multimorbidity. Furthermore, medications given for one condition may adversely affect other outcomes. beta-Blocker use with coexisting cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) is such a situation. OBJECTIVE: To determine the effect of beta-blocker use on cardiac and pulmonary outcomes and mortality in older adults with coexisting COPD and CVD. DESIGN, SETTING, PARTICIPANTS: The study included 1062 participants who were members of the 2004-2007 Medicare Current Beneficiary Survey cohorts, a nationally representative sample of Medicare beneficiaries. Study criteria included age over 65 years plus coexisting CVD and COPD/asthma. Follow-up occurred through 2009. We determined the association between beta-blocker use and the outcomes with propensity score-adjusted and covariate-adjusted Cox proportional hazards. MAIN OUTCOME MEASURES: The 3 outcomes were major cardiac events, pulmonary events, and all-cause mortality. RESULTS: Half of the participants used beta-blockers. During follow-up, 179 participants experienced a major cardiac event; 389 participants experienced a major pulmonary event; and 255 participants died. Each participant could have experienced any >/=1 of these events. The hazard ratio for beta-blocker use was 1.18 [95% confidence interval (CI), 0.85-1.62] for cardiac events, 0.91 (95% CI, 0.73-1.12) for pulmonary events, and 0.87 (95% CI, 0.67-1.13) for death. CONCLUSION: In this population of older adults, beta-blockers did not seem to affect occurrence of cardiac or pulmonary events or death in those with CVD and COPD.

IMPORTANCE: Randomized trials of anti-hypertensive treatment demonstrating reduced risk of cardiovascular events in older adults included participants with less comorbidity than clinical populations. Whether these results generalize to all older adults, most of whom have multiple chronic conditions, is uncertain. OBJECTIVE: To determine the association between anti-hypertensive medications and CV events and mortality in a nationally representative population of older adults. DESIGN: Competing risk analysis with propensity score adjustment and matching in the Medicare Current Beneficiary Survey cohort over three-year follow-up through 2010. PARTICIPANTS AND SETTING: 4,961 community-living participants with hypertension. EXPOSURE: Anti-hypertensive medication intensity, based on standardized daily dose for each anti-hypertensive medication class participants used. MAIN OUTCOMES AND MEASURES: Cardiovascular events (myocardial infarction, unstable angina, cardiac revascularization, stroke, and hospitalizations for heart failure) and mortality. RESULTS: Of 4,961 participants, 14.1% received no anti-hypertensives; 54.6% received moderate, and 31.3% received high, anti-hypertensive intensity. During follow-up, 1,247 participants (25.1%) experienced cardiovascular events; 837 participants (16.9%) died. Of deaths, 430 (51.4%) occurred in participants who experienced cardiovascular events during follow-up. In the propensity score adjusted cohort, after adjusting for propensity score and other covariates, neither moderate (adjusted hazard ratio, 1.08 [95% CI, 0.89-1.32]) nor high (1.16 [0.94-1.43]) anti-hypertensive intensity was associated with experiencing cardiovascular events. The hazard ratio for death among all participants was 0.79 [0.65-0.97] in the moderate, and 0.72 [0.58-0.91] in the high intensity groups compared with those receiving no anti-hypertensives. Among participants who experienced cardiovascular events, the hazard ratio for death was 0.65 [0.48-0.87] and 0.58 [0.42-0.80] in the moderate and high intensity groups, respectively. Results were similar in the propensity score-matched subcohort. CONCLUSIONS AND RELEVANCE: In this nationally representative cohort of older adults, anti-hypertensive treatment was associated with reduced mortality but not cardiovascular events. Whether RCT results generalize to older adults with multiple chronic conditions remains uncertain.

To date, physical exercise is the only intervention consistently demonstrated to attenuate age-related declines in physical function. However, variability exists in seniors' responsiveness to training. One potential source of variability is the insertion (I allele) or deletion (D allele) of a 287 bp fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. This polymorphism is known to influence a variety of physiological adaptions to exercise. However, evidence is inconclusive regarding the influence of this polymorphism on older adults' functional responses to exercise. This study aimed to evaluate the association of ACE I/D genotypes with changes in physical function among Caucasian older adults (n = 283) following 12 mo of either structured, multimodal physical activity or health education. Measures of physical function included usual-paced gait speed and performance on the Short Physical Performance Battery (SPPB). After checking Hardy-Weinberg equilibrium, we used using linear regression to evaluate the genotype*treatment interaction for each outcome. Covariates included clinic site, body mass index, age, sex, baseline score, comorbidity, and use of angiotensin receptor blockers or ACE inhibitors. Genotype frequencies [II (19.4%), ID (42.4%), DD (38.2%)] were in Hardy-Weinberg equilibrium (P > 0.05). The genotype*treatment interaction was statistically significant for both gait speed (P = 0.002) and SPPB (P = 0.020). Exercise improved gait speed by 0.06 +/- 0.01 m/sec and SPPB score by 0.72 +/- 0.16 points among those with at least one D allele (ID/DD carriers), but function was not improved among II carriers. Thus, ACE I/D genotype appears to play a role in modulating functional responses to exercise training in seniors.

BACKGROUND: Adult height has been hypothesized to be inversely associated with coronary heart disease; however, studies have produced conflicting results. We sought to examine the relationship between adult height and the prevalence of coronary artery calcium (CAC), a direct measure of subclinical atherosclerosis and surrogate marker of coronary heart disease. METHODS AND RESULTS: We evaluated the relationship between adult height and CAC in 2703 participants from the National Heart, Lung, and Blood Institute Family Heart Study who underwent cardiac computed tomography. We used generalized estimating equations to calculate the prevalence odds ratios for the presence of CAC (CAC>0) across sex-specific quartiles of height. The mean age of the sample was 54.8 years, and 60.2% of participants were female. There was an inverse association between adult height and CAC. After adjusting for age, race, field center, waist circumference, smoking, alcohol, physical activity, systolic blood pressure, antihypertensive medications, diabetes mellitus, diabetic medications, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipid-lowering medications, and income, individuals in the tallest quartile had 30% lower odds of having prevalent CAC. The odds ratios (95% confidence intervals) for the presence of CAC across consecutive sex-specific quartiles of height were 1.0 (reference), 1.15 (0.86-1.53), 0.95 (0.73-1.22), and 0.70 (0.53-0.93), and P for trend<0.01. There was no evidence of effect modification for the relationship between adult height and CAC by age or socioeconomic status. CONCLUSIONS: The results of our study suggest an inverse, independent association between adult height and CAC.