Optimization of older adults by a geriatric assessment-guided multidisciplinary clinic before CAR T-cell therapy.

ABSTRACT: The optimal means of assessing candidacy of older adults (≥65 years) for chimeric antigen receptor T-cell (CAR-T) therapy are unknown. We explored the role of a geriatric assessment (GA)-guided multidisciplinary clinic (GA-MDC) in selecting and optimizing older adults for CAR-T. Sixty-one patients were evaluated in a GA-MDC (median age, 73 years; range, 58-83). A nonbinding recommendation ("proceed" or "decline") regarding suitability for CAR-T was provided for each patient based on GA results. Fifty-three patients ultimately received CAR-T (proceed, n = 47; decline, n = 6). Among patients who received B-cell maturation antigen (BCMA)-directed (n = 11) and CD19-directed CAR-T (n = 42), the median overall survival (OS) was 14.2 months and 16.6 months, respectively. GA uncovered high rates of geriatric impairment among patients proceeding to CAR-T therapy, with fewer impairments in those recommended "proceed." Patients recommended "proceed" had shorter median length of stay (17 vs 31 days; P = .05) and lower rates of intensive care unit admission (6% vs 50%; P = .01) than those recommended "decline." In patients receiving CD19- and BCMA-directed CAR-T therapy, a "proceed" recommendation was associated with superior OS compared with "decline" (median, 16.6 vs 11.4 months [P = .02]; and median, 16.4 vs 4.2 months [P = .03], respectively). When controlling for Karnofsky performance status, C-reactive protein, and lactate dehydrogenase at time of lymphodepletion, the GA-MDC treatment recommendation remained prognostic for OS (hazard ratio, 3.26; P = .04). Patients optimized via the GA-MDC without serious vulnerabilities achieved promising outcomes, whereas patients with high vulnerability experienced high toxicity and poor outcomes after CAR-T therapy.

Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.

ABSTRACT: Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. In total, 202 patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the 3 most common approaches were intensive chemotherapy (n = 65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n = 65), and DNMTi + venetoclax-based regimens (n = 54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HSCT); median OS was 2.30 years from time of allo-HSCT. Our study demonstrates that survival among patients with MPN-AP/BP is limited in the absence of allo-HSCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches.

First-Line Respiratory Support for Children With Hematologic Malignancy and Acute Respiratory Failure.

OBJECTIVES: To characterize trends in noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) use over time in children with hematologic malignancy admitted to the PICU with acute respiratory failure (ARF), and to identify risk factors associated with NIV failure requiring transition to IMV. DESIGN: Retrospective cohort analysis using the Virtual Pediatric Systems (VPS, LLC) between January 1, 2010 and December 31, 2019. SETTING: One hundred thirteen North American PICUs participating in VPS. PATIENTS: Two thousand four hundred eighty children 0-21 years old with hematologic malignancy admitted to participating PICUs for ARF requiring respiratory support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 3013 total encounters, of which 868 (28.8%) received first-line NIV alone (NIV only), 1544 (51.2%) received first-line IMV (IMV only), and 601 (19.9%) required IMV after a failed NIV trial (NIV failure). From 2010 to 2019, the NIV only group increased from 9.6% to 43.1% and the IMV only group decreased from 80.1% to 34.2% (p < 0.001). The NIV failure group had the highest mortality compared with NIV only and IMV only (36.6% vs. 8.1%, vs. 30.5%, p < 0.001). However, risk-of-mortality (ROM) was highest in the IMV only group compared with NIV only and NIV failure (median Pediatric Risk of Mortality III ROM 8.1% vs. 2.8% vs. 5.5%, p < 0.001). NIV failure patients also had the longest median PICU length of stay compared with the other two study groups (15.2 d vs. 6.1 and 9.0 d, p < 0.001). Higher age was associated with significantly decreased odds of NIV failure, and diagnosis of non-Hodgkin lymphoma was associated with significantly increased odds of NIV failure compared with acute lymphoid leukemia. CONCLUSIONS: For children with hematologic malignancy admitted to the PICU with ARF, NIV has replaced IMV as the most common initial therapy. NIV failure rate remains high with high-observed mortality despite lower PICU admission ROM.

Assessing real-time positive subjective effects of alcohol using high-resolution ecological momentary assessment in risky versus light drinkers.

BACKGROUND: High-resolution ecological momentary assessment (HR-EMA) can assess acute alcohol responses during naturalistic heavy drinking episodes. The goal of this study was to use HR-EMA to examine drinking behavior and subjective responses to alcohol in risky drinkers (moderate-severe alcohol use disorder [MS-AUD], heavy social drinkers [HD]) and light drinkers (LD). We expected that risky drinkers would endorse greater alcohol stimulation and reward, with lower sedation, than LD, even when controlling for amount of alcohol consumed. METHODS: Participants (N = 112; 54% male, M ± SD age = 27.2 ± 4.2 years) completed smartphone-based HR-EMA during one typical alcohol drinking occasion and one non-alcohol-drinking occasion in their natural environment. Participants were prompted to complete next-day surveys that assessed drinking-related outcomes, study acceptability, and safety. RESULTS: HR-EMA prompt completion rates were excellent (92% and 89% for the alcohol and nonalcohol episodes, respectively). The MS-AUD group consumed the most alcohol with the highest estimated blood alcohol concentration (eBAC) by the end of the alcohol drinking episode (0.14 g/dL) versus LD (0.02 g/dL), with HD intermediate (0.10 g/dL). Relative to LD, MS-AUD and HD endorsed greater positive effects of alcohol (stimulation, liking, and wanting). CONCLUSIONS: This study is the first to use HR-EMA to measure and compare real-world acute alcohol responses across diverse drinker subgroups, including persons with MS-AUD. Results demonstrate that risky drinkers experience heightened pleasurable effects measured in real-time during natural-environment alcohol responses. Rather than drinking excessively to eventually achieve desirable subjective effects, risky drinkers show sensitivity to positive alcohol effects throughout a heavy drinking episode.

Predictors of Acute Hematologic Toxicity in Women Receiving Extended-Field Chemoradiation for Cervical Cancer: Do Known Pelvic Radiation Bone Marrow Constraints Apply?

Purpose: Patients with cervical cancer who are at high risk for para-aortic lymphatic involvement may receive extended-field chemoradiation (EF-CRT), with inclusion of the para-aortic region. Increased radiation to bone marrow (BM) may heighten hematologic toxicity (HT) and affect timely delivery of chemoradiation. Factors associated with HT in this setting have not been well studied. Methods and Materials: This study was a retrospective analysis of women treated with EF-CRT from 2012 to 2018 with platinum-based chemotherapy. Factors including age, body mass index (BMI), race, Charlson Comorbidity Index (CCI), and nadirs for white blood cell count, absolute neutrophil count, hemoglobin, and platelet count were collected. The BM metrics included V5Gy, V10Gy, V15Gy, V20Gy, V25Gy, V30Gy, V35Gy, V40Gy and V45Gy (VxGy was defined as the percentage of BM volume receiving x Gy). Hematologic toxicity was defined as grade ≥2 (Cooperative Group Common Toxicity Criteria) leukopenia, anemia, neutropenia, or thrombocytopenia. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using the χ2 test, the Fisher exact test, and logistic regression. Previously published dosimetric BM constraints were examined as detailed in each respective study. Results: Fifty-two women underwent EF-CRT with cisplatin. UVA showed no association between HT and age, BMI, or CCI. When accounting for race, V5Gy ≥98% was associated with grade ≥2 leukopenia (P = .02) and grade ≥2 HT (P = .05). Most previously described radiation metrics were not reproduced in our cohort, but a similar constraint, V20Gy <70%, was associated with reduced leukopenia of grade ≥2 on UVA (P = .02) and MVA (P < .05). Conclusions: Acute HT in patients receiving EF-CRT was associated with large volumes of low-dose radiation to the BM and was also associated with race. Restricting the BM V20Gy to less than 70% to 75% may be beneficial in reducing HT, but other pelvic radiation BM constraints may not be applicable to this population.

Phase I study of nab-paclitaxel-based induction followed by nab-paclitaxel-based concurrent chemotherapy and re-irradiation in previously treated head and neck squamous cell carcinoma.

BACKGROUND: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC. METHODS: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX). RESULTS: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2. CONCLUSIONS: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation. CLINICAL TRIAL INFORMATION: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326.

The Quality Measures Domain in Nursing Home Compare: Is High Performance Meaningful or Misleading?

BACKGROUND AND OBJECTIVES: The reported percent of nursing home residents suffering adverse outcomes decreased dramatically since Nursing Home Compare began reporting them, but the validity of scores is questionable for nursing homes that score well on measures using facility-reported data but poorly on inspections. Our objective was to assess whether nursing homes with these "discordant" scores are meaningfully better than nursing homes that score poorly across domains. RESEARCH DESIGN AND METHODS: We used a convergent mixed-methods design, starting with quantitative analyses of 2012-2016 national data. We conducted in-depth interviews and observations in 12 nursing homes in 2017-2018, focusing on how facilities achieved their Nursing Home Compare ratings. Additional quantitative analyses were conducted in parallel to study performance trajectories over time. Quantitative and qualitative results were interpreted together. RESULTS: Discordant facilities engage in more quality improvement strategies than poor performers, but do not seem to invest in quality improvement in resource-intensive, broad-based ways that would spill over into other domains of quality and change their trajectory of improvement. Instead, they focus on lower-resource improvements related to data quality, staff training, leadership, and communication. In contrast, poor-performing facilities seemed to lack the leadership and continuity of staff required for even these low-resource interventions. DISCUSSION AND IMPLICATIONS: High performance on the quality measures using facility-reported data is mostly meaningful rather than misleading to consumers who care about those outcomes, although discordant facilities still have quality deficits. The quality measures domain should continue to have a role in Nursing Home Compare.

Improving End of Life Cancer Outcomes Through Development and Implementation of a Spiritual Care Advocate Program.

BACKGROUND: Explored whether increased support for spiritual concerns between the healthcare team and patients through the provision of a Spiritual Care Advocate (SCA) would improve end of life outcomes in a metastatic cancer population. DESIGN: Newly diagnosed metastatic cancer patients were recruited at the University of Chicago Medical Center and received spiritual support from a Spiritual Care Advocate during chemotherapy treatments. The final sample consisted of 42 patients (58% of those approached) who completed the baseline survey and had known survival status. MEASUREMENT: Patients completed pre/post surveys measuring spiritual support and palliative quality of life. Baseline measurements of religious practice and externalizing religious health beliefs were also obtained. Receipt of aggressive EOL care was derived from the electronic medical record. RESULT: Median age was 61 years, with 48% Black, and predominantly male (62%). Of the 42 patients, 30 (70%) had died by the time of this analysis. Perceived spiritual support from the medical team increased in 47% of those who received non-aggressive EOL care and by 40% in those who received aggressive EOL care (p=0.012). Patient perceptions of spiritual support from the medical community increased from 27% at baseline to 63% (p=0.005) after the SCA intervention. Only 20% of recipients received aggressive treatments at end of life. CONCLUSION: The SCA model improved the perceived spiritual support between the healthcare team and patients. Although limited by a small sample size, the model was also associated with an improvement in EOL patients' quality of life, spiritual wellbeing, and decreased aggressive EOL care.

Latent trait shared-parameter mixed models for missing ecological momentary assessment data.

Latent trait shared-parameter mixed models for ecological momentary assessment (EMA) data containing missing values are developed in which data are collected in an intermittent manner. In such studies, data are often missing due to unanswered prompts. Using item response theory models, a latent trait is used to represent the missing prompts and modeled jointly with a mixed model for bivariate longitudinal outcomes. Both one- and two-parameter latent trait shared-parameter mixed models are presented. These new models offer a unique way to analyze missing EMA data with many response patterns. Here, the proposed models represent missingness via a latent trait that corresponds to the students' "ability" to respond to the prompting device. Data containing more than 10 300 observations from an EMA study involving high school students' positive and negative affects are presented. The latent trait representing missingness was a significant predictor of both positive affect and negative affect outcomes. The models are compared to a missing at random mixed model. A simulation study indicates that the proposed models can provide lower bias and increased efficiency compared to the standard missing at random approach commonly used with intermittent missing longitudinal data.

Discharge disposition as an independent predictor of readmission among patients hospitalised for community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is the most common non-obstetrical reason for hospital admission, the leading infectious cause of death, and a target for public reporting. CAP has thus become a target of quality improvement and pay-for-performance efforts. However, the relationship between discharge disposition and readmission risk has not been investigated. METHODS: We studied CAP patients admitted to the University of Chicago from 11/2011 to 04/2015. We collected demographic information, comorbidities, laboratory values, vital signs, a modified pneumonia severity index (PSI), length of stay (LOS), clinical instabilities before discharge, discharge disposition and 30-day all-cause readmission. A multivariate logistic regression was performed, specifying readmission as the dependent variable, including as independent variables gender, ethnicity, insurance status, discharge disposition, PSI tertile, the number of clinical instabilities, LOS and comorbidities. RESULTS: Of the 2892 CAP patients identified, 14.9% were readmitted. The distribution of discharge disposition was: 43.0% home without services, 26.1% home with home health care (HHC), 16.2% to a skilled nursing or subacute rehabilitation facility and 14.8% to an acute rehabilitation or long-term acute care facility. Of patients discharged home with HHC, 20.1% were readmitted, compared to 11.5% discharged home without services. In the multivariate regression model, being discharged home with HHC was associated with a markedly greater risk of readmission (Odds ratio 1.58 [95% confidence interval 1.21-2.07]). CONCLUSIONS: Discharge home with HHC is an independent predictor of readmission risk among hospitalised CAP patients. Discharging providers should carefully consider follow-up care and social factors that may impact the risk of readmission among such patients.

Improving Pain Relief in Elder Patients (I-PREP): An Emergency Department Education and Quality Intervention.

OBJECTIVES: To assess the effectiveness of a novel combined education and quality improvement (QI) program for management of pain in older adults in the emergency department (ED). DESIGN: Controlled pre/postintervention examination. SETTING: An academic urban ED seeing 60,000 adult visits annually. PARTICIPANTS: Individuals aged 65 and older experiencing moderate to severe pain. INTERVENTION: Linked standardized education and continuous QI for multidisciplinary staff in an urban, academic ED from January 2012 to January 2014. MEASUREMENTS: Pain intensity, percentage receiving and time to pain assessment and reassessment, percentage receiving and time to delivery of analgesic. RESULTS: The percentage of participants with final pain score of 4 or less (out of 10) increased 47.5% (95% confidence interval (CI) = 41.8-53.2%). Median decrease in pain intensity improved significantly, from 0.0 to 5.0 points (P < .001). Median final pain score decreased from 7.0 to 4.0 points (P < .001). The percentage of participants with any pain improvement increased 43.7% (95% CI = 37.1-50.3%, P < .001). Pain reassessments increased significantly (from 51.9% to 82.5%, P < .001). The percentage receiving analgesics increased significantly (from 64.1% to 84.8%, P < .001). After the intervention, participants had 3.1 (95% CI = 2.1-4.4, P < .001) greater odds of receiving analgesics and 4.7 (95% CI = 3.5-6.5, P < .001) greater odds of documented pain reassessment. CONCLUSION: The I-PREP intervention substantially improved pain management in older adults in the ED with moderate to severe musculoskeletal or abdominal pain. Significant reductions in pain intensity were achieved, the timing of pain assessments and reassessments was improved, and analgesics were delivered faster. Tightly linking education to targeted QI improved pain management of older adults in the ED.

Lifestyle intervention and cardiovascular disease risk reduction in low-income Hispanic immigrant women participating in the Illinois WISEWOMAN program.

Cardiovascular disease (CVD) is the leading cause of death for Hispanic women in the United States. In 2001, the Illinois Department of Public Health received funding from the Centers for Disease Control and Prevention to implement the enhanced WISEWOMAN program (IWP) to address the disproportionate CVD risk among uninsured and underinsured women enrolled in the Illinois Breast and Cervical Cancer Early Detection Program. This paper presents the results of the Spanish-language arm of the IWP. Spanish speaking IWP participants were recruited from two sites, and randomized into either the minimum intervention (MI) or the enhanced intervention (EI) group. Both groups received CVD risk factor screening and educational handouts. The EI group also received an integrated 12-week nutrition and physical activity lifestyle change intervention. Of the 180 Spanish-speaking immigrants in this sample, 90 (50%) received the EI and 90 (50%) received the MI. At baseline there were no significant differences between group demographics or clinical values. At post-intervention, the EI group showed improvements in fat intake, fiber intake, moderate intensity physical activity, and total physical activity. At 1 year only the change in fiber intake remained. A significant improvement was also seen in body mass index (BMI) at the 1-year follow-up. The IWP Spanish-language arm was moderately successful in addressing risk factors for CVD in this population. The behavior changes that sustained up to a year were an increase in fiber intake and a decrease in BMI.

Does self-management counseling in patients with heart failure improve quality of life? Findings from the Heart Failure Adherence and Retention Trial (HART).

PURPOSE: Heart failure (HF) is associated with poor health-related quality of life (HRQOL). The purpose of our study is to determine the effect of a self-management intervention on HRQOL domains across time, overall, and in prespecified demographic, clinical, and psychosocial subgroups of HF patients. METHODS: HART was a single-center, multi-hospital randomized trial. Patients (n = 902) were randomized either to a self-management intervention with provision of HF educational information or an enhanced education control group which received the same HF educational materials. HRQOL was measured by the Quality of Life Index, Cardiac Version, modified, and the Medical Outcomes Study 36-item Short-Form Health Survey physical functioning scale. Analyses included descriptive statistics and mixed-effects regression models. RESULTS: In general, overall, study participants' HRQOL improved over time. However, no significant differences in HRQOL domain were detected between treatment groups at baseline or across time (p > 0.05). Subgroup analyses demonstrated no differences by treatment arm for change in HRQOL from baseline to 3 years later. CONCLUSIONS: We conclude that in our cohort of patients, the self-management intervention had no benefit over enhanced education in improving domains of HRQOL and HRQOL for specified HF subgroups.

Sleep duration and weight change in midlife women: the SWAN sleep study.

OBJECTIVE: Short sleep duration has been associated with higher current BMI and subsequent weight gain. However, most prior longitudinal studies are limited by reliance on self-reported sleep duration, and none accounted for the potential confounding effect of sleep-disordered breathing. The associations of sleep duration with current BMI and BMI change were examined among 310 midlife women in the Study of Women's Health Across the Nation (SWAN) Sleep Study (2003-2005). METHODS: Sleep duration was assessed for approximately one month with concurrent wrist actigraphy and sleep diaries. The presence and severity of sleep-disordered breathing was quantified using the apnea-hypopnea index (AHI) based on in-home polysomnography. BMI was assessed annually through core SWAN visit 10 (2006 and 2008). RESULTS: Mean BMI increased from 29.6 (SD = 7.8) kg/m(2) to 30.0 (SD = 8.0) kg/m(2) over an average of 4.6 years (SD = 1.0) of follow-up. In cross-sectional analyses controlling for AHI, demographic variables, and several potential confounding variables, actigraphy (estimate = -1.22, 95% confidence interval (CI): -2.03, -0.42) and diary (estimate = -0.86, 95% CI -1.62, -0.09) measures of sleep duration were inversely associated with BMI. Each hour of less sleep was associated with 1.22 kg/m(2) greater BMI for actigraphy sleep duration, and a 0.86 kg/m(2) greater BMI for diary sleep duration. Longitudinal associations between sleep duration and annual BMI change were nonsignificant in unadjusted and fully adjusted models. CONCLUSION: In this cohort of midlife women, cross-sectional associations between sleep duration and current BMI were independent of sleep-disordered breathing, but sleep duration was not prospectively associated with weight change.

Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

Lifestyle intervention and cardiovascular risk reduction in the Illinois WISEWOMAN Program.

BACKGROUND: The Illinois WISEWOMAN Program (IWP) was designed to address the disproportionate risk of cardiovascular disease (CVD) among disadvantaged, low-income women. In total, 1021 women aged 40 to 64 years were recruited from the Illinois Breast and Cervical Cancer Program. The women were randomized to either a minimum intervention (MI) or an enhanced intervention (EI) group. Both groups received CVD risk factor screening and educational materials, and the EI group received a 12-week lifestyle change intervention. METHODS: Demographic and clinical data were collected in addition to data on CVD risk, which was measured in terms of nutritional and physical activity behavior, using culturally adapted versions of three valid and reliable questionnaires. IWP data were analyzed for demographic characteristics and clinical and behavioral outcomes at baseline, post-intervention, and follow-up at 1 and 2 years from baseline. This article reports the change in these outcomes up to the 1-year follow-up. RESULTS: Participants in the EI group showed significant improvement on some of the dietary and physical activity outcomes both at post-intervention and 1-year follow-up. Compared with the MI group, the EI group showed more improvement in dietary fat- and fiber-related behaviors and increased physical activity levels. There were improvements in all of the cardiovascular outcomes at post-intervention in both the EI and MI groups; however, these changes were not statistically significant. CONCLUSION: As an integrated physical activity and nutrition intervention, the IWP has shown its strength in addressing some of the lifestyle behaviors for CVD prevention in this at-risk target population.

Depressive symptoms are related to progression of coronary calcium in midlife women: the Study of Women's Health Across the Nation (SWAN) Heart Study.

BACKGROUND: Major depression and depressive symptoms are associated with cardiovascular disease (CVD), but the impact of depression on early atherogenesis is less well known, particularly in women and minorities. This study examined whether depressive symptoms are associated with progression of coronary artery calcification (CAC) among women at midlife. METHODS: The SWAN is a longitudinal, multisite study assessing health and psychologic factors in midlife women. An ancillary study (SWAN Heart) evaluated subclinical atherosclerosis in women who reported no history of CVD or diabetes. In 346 women, CAC was measured twice by electron beam computed tomography, an average of 2.3 years apart. Progression, defined as an increase by ≥10 Agatston units, was analyzed using relative risk (RR) regression. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: Progression of CAC was observed in 67 women (19.1%). Each 1-SD-higher CES-D score at baseline related to a 25% increased risk of CAC progression (RR 1.25, 95% CI 1.06-1.47, P = .007), adjusting for age, time between scans, ethnicity, education, menopausal status, and known CVD risk factors. This risk was similar to the risk induced by body mass index (RR 1.31, 95% CI 1.11-1.54, P = .001) and systolic blood pressure (RR 1.28, 95% CI 1.06-1.55, P = .01). CONCLUSIONS: Depressive symptoms were independently associated with progression of CAC in this cohort of midlife women. Depressive symptoms may represent a risk factor that is potentially modifiable for early prevention of CVD in women.

Vitamin D is associated with atheroprotective high-density lipoprotein profile in postmenopausal women.

BACKGROUND: Low vitamin D has been associated with low levels of high-density lipoprotein (HDL) cholesterol, a marker of coronary risk. Whether atheroprotective HDL particle composition accounts for this association and whether fat affects this association is not known. OBJECTIVE: To explore the association between HDL particle composition and 25-hydroxy vitamin D (25[OH]D) in post-menopausal women. METHODS: Vitamin D levels and lipoprotein composition were assessed in fasting blood samples of apparently healthy women from a diverse Chicago community. Visceral (VAT) and subcutaneous (SAT) abdominal fat area were assessed using computed tomography. Total body fat mass was measured by dual-energy X-ray absorptiometry. RESULTS: We enrolled 78 women (50% black; 50% white), age 48 to 64 years, all of whom were participants in a longitudinal study of fat patterning. They had a mean 25[OH]D of 31 ± 15 µg/L, HDL cholesterol 57±11 mg/dL, and large HDL particle subclass 8.6±3.4 µmol/L. In a multivariable-adjusted regression model, each 5 µg/L higher 25[OH]D predicted 0.57 µmol/L (95%CI 0.20-0.95) higher large HDL particles, independent of race, season, and total HDL particle concentration. This association was only partially confounded by total body fat mass (0.49, 95%CI 0.10-0.89), SAT (0.50, 95%CI 0.11-0.90), or VAT (0.37, 95%CI 0.01-0.74). Age did not significantly influence the strength of associations. CONCLUSIONS: Higher 25[OH]D levels are associated with large HDL particles. This association is stronger than that of HDL cholesterol and only partially confounded by body fat. Theoretically, vitamin D may protect against cardiovascular risk by promoting formation of large HDL particles, affecting reverse cholesterol transport.