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Objective: To describe and identify associated factors for patient–clinician discordance of disease assessment at biologic or Janus kinase inhibitor (JAKi) initiation and over 12 months following initiation in patients with rheumatoid arthritis (RA) from a US RA registry. Methods: Analyses included CorEvitas RA Registry patients who initiated their first biologic or JAKi on or after February 1, 2015, and had 6‐ and 12‐month follow‐up visits. Positive discordance was defined as patient global assessment (visual analog scale [VAS‐100]) minus physician's global assessment (VAS‐100) equal to 30 points or more. Persistent discordance was defined as positive discordance at all three visits. Mixed‐effects logistic regression was used to determine risk factors for positive discordance at initiation and for persistent discordance. Results: Among 2227 first‐time biologic/JAKi‐initiating patients, 613 had both follow‐up visits available and were included in initiation visit analyses, and of these, 163 had positive discordance at initiation and were included in persistent discordance analyses. About 30% of all patients had positive discordance at any visit, and one third of these (10% total) were persistent at all three visits. Multivariable analyses revealed that worse scores on the Clinical Disease Activity Index, greater patient‐reported pain and fatigue, and greater functional impairment were associated with positive discordance at the time of therapy initiation. Being disabled versus working full‐time and being female were associated with higher odds and having Medicare versus no insurance was associated with lower odds of having persistent positive discordance. Conclusion: Results suggest positive discordance is common among real‐world patients with RA initiating their first biologic or JAKi. The identified risk factors associated with patient–clinician discordance will help clinicians foster a more patient‐centric discussion in treatment decisions. [ABSTRACT FROM AUTHOR]

Introduction: The 2018 American Heart Association (AHA)/American College of Cardiology (ACC)/Multisociety blood cholesterol guidelines recommend clinicians consider adding non-statin therapy for patients with very high-risk (VHR) atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl while receiving maximally tolerated statins. However, according to a recent study, only 17.1% of patients with established ASCVD received appropriate lipid-lowering therapy (LLT) intensification. Here, we describe the design of a prospective, 12-month study (LOGAN-CV) evaluating a multifaceted site-level intervention to enhance clinicians' adherence to guidelines to improve LDL-C levels for patients with VHR ASCVD. Methods: Clinicians from up to ten research sites are eligible if they care for adult patients with ASCVD. Interventions include educational modules, a cloud-based performance platform providing clinicians a tailored summary of their LDL-C management performance, newsletters, periodic peer-to-peer calls, and pre- and post-intervention surveys evaluating knowledge, attitudes, and beliefs around LDL-C management, with additional interventions for clinicians demonstrating a lower readiness to make treatment decisions based on guideline recommendations. Patients with VHR ASCVD, defined as having recent myocardial infarction and LDL-C ≥ 70 mg/dl despite statin treatment, will be included in the study. Patient data will be collected from electronic medical records from baseline (clinician enrollment) through the 12-month intervention. The study started in October 2022, with anticipated completion in March 2024. Planned Outcomes: The change in proportion of patients with LDL-C < 70 mg/dl achieved at any time during the 12-month intervention (primary); LLT intensification, changes in guideline-aligned LDL-C testing and LLT titration over 12 months, and change in overall clinicians' knowledge, attitudes, and beliefs are key outcomes of interest. The LOGAN-CV study addresses a critical unmet need in LDL-C control in patients with VHR ASCVD and evaluates the effect of a multifaceted intervention targeting clinicians to improve their adherence to guidelines and consequently improve clinical outcomes for patients. [ABSTRACT FROM AUTHOR]

Introduction: The burden of persistent (≥ 3 days) severe AKI (PS-AKI) is poorly described among inpatients with stage 2-3 AKI in the ward or ICU. Quantification could motivate targeted interventions to decrease duration of AKI in these high-risk patients.Methods: This retrospective cohort study included adult patients discharged from January 1, 2017, to December 31, 2019, from US hospitals in the PINC AI Healthcare Database. Patients with KDIGO stage 2 or 3 AKI, length of stay (LOS) ≥3 days, ≥3 serum creatinine measures, and no history of renal transplant, dialysis, or stage 5 chronic kidney disease (CKD) were included. Patients were classified as PS-AKI (stage 3 AKI lasting ≥3 days or with death in ≤ 3 days, or stage 2 or 3 AKI with dialysis in ≤ 3 days) or not persistent severe AKI (NPS-AKI)(stage 3 AKI for ≤ 2 days, or stage 2 AKI without dialysis in ≤ 3 days). Outcomes during index (initial) hospitalization were PS-AKI incidence, ICU use and in-hospital mortality, and during 30-day (post-discharge) were readmissions, in-hospital mortality, dialysis, and "new" dialysis (dialysis among patients without dialysis during index hospitalization). For index outcomes, we used a sensitivity definition, PS-AKISens, that excluded patients who met PS-AKI criteria by dialysis/death in ≤ 3 days of AKI onset. Multivariable-adjusted logistic regression quantified differences between PS-AKI and NPS-AKI, overall, and separately for ICU and non-ICU patients.Results: Among 126,528 inpatients with stage 2 or 3 AKI, PS-AKI developed in 24.4% (30,916), with 39% of PS-AKI occurring in non-ICU patients. With NPS-AKI as the reference group, adjusted odds ratios (aORs) (95% CI) for PS-AKI and for PS-AKISens were 2.15 (2.09-2.21) and 1.28 (1.24-1.32) for ICU use and 4.58 (4.41-4.75) and 1.79 (1.70-1.89) for in-hospital mortality during index hospitalization. For outcomes during 30-days post-discharge, aORs for PS-AKI vs. NPS-AKI were 1.07 (1.02-1.11) for readmissions, 1.33 (1.18-1.49) for in-hospital mortality, 15.66 (13.87-17.67) for dialysis, and 6.80 (5.84-7.93) for new dialysis. Despite higher mortality among ICU patients, aORs for outcomes during index and 30-days post-discharge were similar for ICU and non-ICU patients.Discussion/conclusion: In and out of the ICU, PS-AKI frequently affected inpatients with stage 2 or 3 AKI and was independently associated with worse clinical outcomes during index hospitalization and during 30-days post-discharge. These results suggest that interventions to prevent persistence of severe AKI may reduce adverse clinical outcomes among patients with stage 2 or 3 AKI in or out of the ICU. [ABSTRACT FROM AUTHOR]

After an initial decline from April through June 2020 (from 22.2% to 11.9%), adjusted in-hospital mortality in coronavirus disease 2019 (COVID-19) inpatients peaked twice and was significantly higher than June 2020 for subsequent months except in July and October 2020. Adjusted mortality trends differed across age groups between November 2020 and February 2021. [ABSTRACT FROM AUTHOR]

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening systemic and chronic autoinflammatory disease characterized by sterile, neutrophilic pustules. The standard of care for GPP varies by region, with limited information and experience of flares and their treatment. Our aim was to establish current unmet needs in GPP by better understanding the natural history of GPP, examining how dermatologists diagnose GPP and GPP flares, and establishing the range and adequacy of GPP treatment options currently prescribed by dermatologists. Methods: Eligible dermatologists (N = 29) completed a 28-question structured survey, covering ten themes, ranging from GPP diagnostic criteria to GPP symptoms and treatment. Results: All dermatologists stated that pustules were necessary to diagnose a GPP flare. The most frequently reported triggering factors for GPP were steroid withdrawal (64%), infection (58%), and stress (50%). Most dermatologists indicated that available treatment options for GPP flares were adequate "most" (79%) or "all" (14%) of the time. Despite this reported adequacy, 38% of dermatologists reported that it was at least "somewhat common" for a flare to require hospitalization. Furthermore, 72% of dermatologists indicated that treatments were too slow to control flares, and 66% indicated that treatments did not adequately prevent new flares at least "sometimes". Conclusion: This survey suggests that there are key features of GPP flares, and could initiate discussion around forming consensus guidelines for diagnosis and management. While the results suggest that moderately effective therapies may exist, the need for GPP-specific treatments remains. [ABSTRACT FROM AUTHOR]

Background: Light to moderate alcohol consumption has been variably associated with lower or higher risk of dementia, but effects on Alzheimer's disease pathology are less clear.Objective: We determined whether late-life alcohol consumption was associated with Alzheimer's disease pathology among older adults.Methods: We assessed the associations of alcohol consumption self-reported in 2000-2002 with brain amyloid-β deposition on PET scans, and white matter lesion and hippocampal volume on MRIs measured 7-9 years later in 189 participants of the Ginkgo Evaluation of Memory Study (age 75-87 years at baseline) who were free of clinical dementia, using multivariable-adjusted and inverse probability-weighted robust linear regression models.Results: Alcohol consumption was not statistically significantly associated with amyloid-β deposition (standardized uptake value ratio difference per drink: -0.013 [95% CI: -0.027, 0.002]). Both non-drinkers and participants consuming ≥1 drink(s)/week had higher white matter lesion volume (% intracranial volume) than did the reference group of those consuming <1 drink/week (differences: 0.25 % [95% CI: 0.01, 0.50]; 0.26 % [95% CI: 0.02, 0.50]). The association of alcohol consumption and hippocampal volume was modified by age (p = 0.02). Among participants younger than 77 years, participants consuming 1-7 drinks/week had larger hippocampal volume compared with participants consuming <1 drink/week.Conclusions: Alcohol consumption was not statistically significantly associated with amyloid-β deposition 7-9 years later. Non-drinking and greater alcohol consumption were associated with higher white matter lesion volume compared with drinking <1 drink/week. Moderate drinking was associated with higher hippocampal volume in younger individuals. Given the selective nature of this population and adverse health effects of excessive alcohol consumption, these findings warrant further investigation, but cannot be translated into clinical recommendations. [ABSTRACT FROM AUTHOR]

Cardiovascular disease risk factors, including age, hypertension, and diabetes, contribute to aortic stiffness and subclinical cardiovascular and brain disease, increasing dementia risk. Aortic stiffness, measured by carotid-femoral pulse wave velocity (cfPWV), reduces the buffering of pulsatile blood flow, exposing cerebral small arteries to microvascular damage. High cfPWV is related to white matter hyperintensities and brain amyloid deposition, and to cognitive decline, but it is unclear whether cfPWV independently predicts incident dementia. Therefore, we tested the hypothesis that cfPWV predicts incident dementia in older adults, independent of potential confounders. The Cardiovascular Health Study Cognition Study followed 532 non-demented older adults with annual cognitive exams from 1998-99 through 2013. CfPWV was measured on 356 (mean age = 78, 59% women) between 1996-2000. Over 15 years, 212 (59.6%) developed dementia (median time from cfPWV measurement = 4 years). In age and sex-adjusted Cox models, cfPWV was significantly associated with increased risk of dementia, but systolic blood pressure, mean arterial pressure and pulse pressure were not. CfPWV (transformed as - 1/cfPWV) remained significantly associated with dementia risk when further adjusted for education, race, APOEɛ4, diabetes, body mass index, mean arterial pressure, and anti-hypertensive medication (hazard ratio = 1.60, 95% CI = 1.02, 2.51). Results were similar when further adjusted for baseline global cognition, subclinical brain measures, and coronary artery calcification. Finally, higher cfPWV was related to lower physical activity intensity and higher systolic blood pressure, heart rate, and waist circumference measured 5 years prior. An important unanswered question is whether interventions to slow arterial stiffening can reduce the risk of dementia. [ABSTRACT FROM AUTHOR]

Background The concentration and size of lipoprotein particles are associated with race, inflammation, and disease. When triglycerides are high, as in pregnancy, lipoprotein particle size may have physiologic importance beyond conventional lipid measurements. We considered that lipoprotein particles may be related to preterm birth (PTB) and explored race differences. Materials and Methods Samples were collected at 9 weeks' gestation (22 PTB [< 37 weeks]; 42 term births [≥ 37 weeks]). Lipids were assayed using standard techniques. Concentrations of high-density lipoprotein, low-density lipoprotein, and very low- density lipoprotein particles (HDL-P, LDL-P, and VLDL-P, respectively) and markers of systemic inflammation were quantified using nuclear magnetic resonance spectroscopy and related to PTB. Results Women with PTB had lower VLDL-P (- 10.66 nmol/L, p = 0.03) and higher systemic inflammation (+ 19.2 µmol/L, p = 0.02) compared with women with term births, independent of race, pre-pregnancy body mass index, and smoking. Black versus white women had lower VLDL-P and higher HDL cholesterol (both p < 0.05). Race-specific results indicated that large HDL-P and inflammation (glycoprotein B) were higher with PTB versus term birth among black women only. Conclusion Women with PTB had lower VLDL-P early in pregnancy, which may represent impaired lipid response. Black-white differences in the lipoprotein profile are similar to nonpregnant adults, but race-specific lipoprotein and inflammation associations with PTB warrant further study. [ABSTRACT FROM AUTHOR]

Specific alleles of the human leukocyte antigen (HLA)-DRB1 gene (HLA-DRB1) encode a "shared epitope" (SE) associated with rheumatoid arthritis (RA), especially more severe cyclic-citrullinated peptide antibody-positive (anti-CCP+) RA. We evaluated associations of number of SE alleles (0, 1, or 2) with total and cardiovascular disease (CVD) mortality and incident coronary heart disease (CHD), CVD, and cancer over a mean 8.9 (standard deviation, 3.5) years of follow-up, stratifying by baseline anti-CCP status (positive (+) vs. negative (-)). A longitudinal study, the Women's Health Initiative RA Study (1993-2010), sampled postmenopausal women who reported RA at baseline (1993-1998) or follow-up in the Women's Health Initiative, classified as anti-CCP+ RA (n = 556) or anti-CCP- non-RA (n = 1,070). Among anti-CCP+ RA women, SE alleles were not related to age-adjusted risks of CHD, CVD, or cancer or to total or CVD mortality. Among anti-CCP- non-RA women, age-adjusted hazard ratios for 1 and 2 SE alleles versus 0 SE alleles were 0.41 (95% confidence interval (CI): 0.34, 0.50) and 0.44 (95% CI: 0.27, 0.72), respectively, for CVD; 0.43 (95% CI: 0.37, 0.53) and 0.30 (95% CI: 0.16, 0.64), respectively, for CHD; and 0.62 (95% CI: 0.53, 0.73) and 0.52 (95% CI: 0.33, 0.83), respectively, for cancer. Associations persisted after adjustment for CVD risk factors, joint pain, rheumatoid factor positivity, and inflammatory markers (white blood cell count or cytokine level). In future studies, investigators should evaluate SE associations among anti-CCP- adults without RA and potential mechanisms. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is highly prevalent at ages 80 and above. The association of physical functioning (PF), a key to an optimal aging trajectory, with CVD and specific CVD diagnosis in women who survive to age 80 and above has not been described previously and has important public health significance given our aging population.Methods: Women's Health Initiative participants aged 80 years or older at the time of self-reporting PF (RAND SF-36) were studied in relationship to CVD diagnosis, whether present at study baseline (1993-1998) or diagnosed during follow-up through 2012. Cross-sectional analyses utilized demographic, medical, lifestyle, and psycho-social questionnaire data from baseline or updated at the time of self-reported PF.Results: Among 27,145 older Women's Health Initiative participants, 22.0% (N = 5,959) had been diagnosed with CVD, specifically: 11.3% (N = 3,071) with coronary heart disease; 4.7% (N = 1,279), stroke; 5.2% (N = 1,397), venous thromboembolism; 2.7% (N = 737), peripheral arterial disease; and 2.7% (N = 725), congestive heart failure. PF scores (mean ± SE) were significantly (p < .0001) higher without CVD (60.0 ± 26.9), compared with any CVD (47.9 ± 27.3), and for each specific CVD diagnosis: coronary heart disease (48.8 ± 27.1); stroke (44.8 ± 27.9); venous thromboembolism (48.9 ± 27.4); peripheral arterial disease (41.9 ± 2.2); and congestive heart failure (38.8 ± 26.1). Regardless of CVD diagnosis, higher PF was associated with: younger age at the time of PF assessment; lower body mass index; higher recreational physical activity; better self-reported general health; fewer hip fractures after age 55; no history of arthritis; and no recent use of non-steroidal anti-inflammatory drugs.Conclusions: Older women with any CVD, and particularly women with congestive heart failure or peripheral arterial disease, reported significantly lower PF compared to women with no CVD. Regardless of CVD diagnosis, higher PF was strongly associated with a more active lifestyle and lower body mass index, suggesting potential intervention targets for more optimal aging. [ABSTRACT FROM AUTHOR]

A response is presented from the author of the article "Rheumatoid arthritis, anti-cyclic citrullinated peptide positivity, and cardiovascular disease risk in the Women's Health Initiative" published in a 2015 issue.

Objective. To evaluate the incidence of cardiovascular disease (CVD) morbidity and mortality over the course of 10 years among the more than 160,000 postmenopausal women in the Women's Health Initiative (WHI) in relation to self-reported rheumatoid arthritis (RA), taking diseasemodifying antirheumatic drugs (DMARDs), anti-cyclic citrullinated peptide (anti-CCP) positivity, rheumatoid factor (RF) positivity, CVD risk factors, joint pain, and inflammation (white blood cell count and interleukin-6 levels). Methods. Anti-CCP and RF were measured in a sample of WHI participants with self-reported RA (n5 9,988). RA was classified as self-reported RA plus anti-CCP positivity and/or taking DMARDs. Anti-CCP- negative women with self-reported RA and not taking DMARDs were classified as having "unverified RA". Results. Age-adjusted rates of coronary heart disease (CHD), stroke, CVD, fatal CVD, and total mortality were higher in women with RA than in women with no reported RA, with multivariable-adjusted hazard ratios of 1.46 (95% confidence interval [95% CI] 1.17-1.83) for CHD and 2.55 (95% CI 1.86-3.51) for fatal CVD. Among women with RA, anti-CCP positivity and RF positivity were not significantly associated with higher risk of any outcomes, despite slightly higher risk of death for those who were anti-CCP positive than for those who were anti-CCP negative. Joint pain severity and CVD risk factors were strongly associated with CVD risk, even in women with no reported RA. CVD incidence was increased in women with RA versus women with no reported RA at almost all risk factor levels, except for low levels of joint pain or inflammation. Among women with RA, inflammation was more strongly associated with fatal CVD and total mortality than with CHD or CVD. Conclusion. Among postmenopausal women, RA was associated with 1.5-2.5-fold higher CVD risk. CVD risk was strongly associated with CVD risk factors, joint pain severity, and inflammation, but not with anti-CCP positivity or RF positivity. [ABSTRACT FROM AUTHOR]

OBJECTIVE In the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated associations of baseline levels of a lipoprotein-based insulin resistance (IR) index (LP-IR), IR-related lipoprotein particles, mean particle sizes, and lipids, with incident type 2 diabetes, independent of confounders, glucose, insulin, and HOMA-IR. RESEARCH DESIGN AND METHODS Among 5,314 adults aged 45-84 years without baseline diabetes or cardiovascular disease, 656 cases of diabetes were identified during a mean follow-up of 7.7 years. Lipoprotein particle concentrations, size, and LP-IR were determined by nuclear magnetic resonance spectroscopy of stored baseline plasma. Potential effect modification, by race/ethnicity, sex, baseline use of lipid-lowering medications or hormone therapy, or glucose strata (<90, 90-99, and ≥100 mg/dL), was also evaluated. RESULTS Higher levels of LP-IR, large VLDL particles (VLDL-P), small LDL particles, triglycer-ides (TG), and TG-to-HDL cholesterol (HDL-C) ratio and lower levels of large HDL particles, smaller HDL and LDL size, and larger VLDL size were significantly associated with incident diabetes adjusted for confounders and glucose or insulin. These also were similar by race/ethnicity, sex, and treatment group. Associations were similar for LP-IR, large VLDL-P, mean VLDL size, TG, and TG-to-HDL-C ratio; they persisted for LP-IR, large VLDL-P, or mean VLDL size adjusted for HOMA-IR or TG-to-HDL-C ratio and glucose but not for the TG-to-HDL-C ratio adjusted for LP-IR or for HOMA-IR or insulin if adjusted for LP-IR and glucose. CONCLUSIONS Among ethnically diverse men and women, LP-IR, large VLDL-P, large VLDL size, TG, and TG-to-HDL-C ratio were associated with incident diabetes independent of established risk factors, glucose, insulin, or HOMA-IR, as well as the use of lipid-lowering medications or hormone therapy. [ABSTRACT FROM AUTHOR]

Second-generation assays for anti-cyclic citrullinated peptide (anti-CCP), a highly sensitive and specific marker for rheumatoid arthritis (RA), have redefined the epidemiology of RA. In the Women's Health Initiative (WHI) RA study (2009–2011), we evaluated the prevalence of anti-CCP positivity among 15,691 (10.2% of 161,808) WHI participants aged 50–79 years who reported RA. Using stored baseline specimens, we measured serum anti-CCP, rheumatoid factor (RF), and antinuclear antibody in a defined sample of 9,988 of black, white, and Hispanic women. In a subset of women, we measured plasma cytokine levels and number of copies of the human leukocyte antigen (HLA)-DRB1 (HLA-DRB1) shared epitope in DNA by means of Luminex polymerase chain reaction typing (Luminex Corporation, Austin, Texas). We validated classification of probable clinical RA in 2 clinics as anti-CCP positivity or self-reported validated use of disease-modifying antirheumatic drugs (DMARDs). The prevalence of anti-CCP positivity was 8.1%, and the prevalence of RF positivity was approximately 16.0%. DMARD use including prednisone was reported by 1,140 (11.4%) participants (841 excluding prednisone) but by 57.5% of anti-CCP-positive women. The prevalence of 2 shared epitopes was also much higher for anti-CCP-positive women (18.2%, as opposed to only 5.5% for women with anti-CCP-negative DMARD-positive RA and 6.6% for anti-CCP-negative, RF-negative DMARD nonusers). Median cytokine levels were much higher for anti-CCP-positive/RF-positive women. Women with anti-CCP-positive RA and anti-CCP-negative RA had different characteristics with regard to HLA shared epitope, cigarette smoking, and inflammation (cytokines). [ABSTRACT FROM AUTHOR]

Objective To compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI ≥ 40), and examine heterogeneity in weight-related CHD risk. Methods Among 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF). Results Mortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for. Conclusions Severe obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity. [ABSTRACT FROM AUTHOR]

Objective Nearly, a third of obese individuals, termed metabolically benign obese, have a low burden of adiposity-related cardiometabolic abnormalities, whereas a substantial proportion of normal-weight individuals possess risk factors. Methods In cross-sectional analyses of 699 normal weight and 1,294 overweight/obese postmenopausal women enrolled in a nested case-control stroke study ancillary to the Women's Health Initiative Observational Study, we compared levels of adiponectin, leptin, and resistin among metabolically benign normal weight, at-risk normal weight, metabolically benign obese, and at-risk obese women using components of the ATP III definition of the metabolic syndrome (metabolically benign: ≤1 of the four components; at-risk phenotype: ≥2 components or diabetes). Results Overall, 382/699 normal-weight women (54.6%) and 328/1,194 overweight/obese women (27.5%) were metabolically benign. Among normal-weight women, at-risk women had higher leptin and lower adiponectin levels compared to metabolically benign women; multivariate-adjusted odds ratios were significant for having leptin (OR: 2.51; 95% CI: 1.28-5.01) and resistin (1.46; 1.03-2.07) in the top tertile and adiponectin in the bottom tertile (2.64; 1.81-3.84). Compared to metabolically benign overweight/obese women, at-risk obese women had higher odds of having leptin in the top tertile (1.62; 1.24-2.12) and adiponectin in the bottom tertile (2.78; 2.04-3.77). Conclusions Overall, metabolically benign overweight/obese women had an intermediate adipokine profile (between at-risk obese and metabolically benign normal-weight women), whereas at-risk normal-weight women had a less favorable profile compared to metabolically benign normal-weight women. As adiponectin was the only adipokine independent of BMI, it may be most likely to have a role in the etiological pathway of these phenotypes. [ABSTRACT FROM AUTHOR]

Objective Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD) and mortality. We measured anti-cyclic citrullinated peptide (anti-CCP) antibody levels and determined use of disease-modifying antirheumatic drugs (DMARDs) among women in the Women's Health Initiative (WHI). Using these data, we undertook this study to assess total mortality over 10 years of followup among white, black, or Hispanic women with self-reported RA in the WHI. Methods Using stored baseline serum, we measured anti-CCP, rheumatoid factor (RF), and antinuclear antibodies (ANAs) in 9,988 women who reported having RA. Based on a previous chart review study, probable RA was defined as either self-reported RA and anti-CCP positivity, or anti-CCP negativity and DMARD use. Cox proportional hazards regression was used to model the relationship of self-reported RA, DMARD exposure, and anti-CCP positivity to total mortality, using followup data through April 2009. Results At baseline, the mean age was 62.8 years; 24.5% of subjects were black and 10% were Hispanic. Prevalence of anti-CCP positivity was 8.1% (n = 812), and 217 women were anti-CCP negative but had reported use of DMARDs; therefore, 1,029 women (of 9,988) were classified as having probable RA, and 8,958 were classified as unlikely to have RA (with data on DMARD use missing for 1 subject). Age-adjusted mortality rates were ∼2-fold higher for anti-CCP-positive women, with 20.2 deaths per 1,000 person-years, as compared to 11.4 deaths per 1,000 person-years among anti-CCP-negative women with self-reported RA who never used DMARDs. Among women who did not report any arthritis at baseline, we found 8.3 deaths per 1,000 person-years. The increased risk among anti-CCP-positive women with RA was not explained by age, RF positivity, ANA positivity, or DMARD use. Conclusion Anti-CCP-positive RA was associated with substantial excess mortality among postmenopausal women in the WHI. This result was not explained by the risk factors we measured. [ABSTRACT FROM AUTHOR]

Background Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors. Methods A population-based sample of healthy 784 men aged 40–49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this crosssectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system. Results cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking. Conclusions Among healthy men aged 40 – 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs. [ABSTRACT FROM AUTHOR]

Using data from the Women's Health Initiative (1993–2009; n = 158,833 participants, of whom 84.1% were white, 9.2% were black, 4.1% were Hispanic, and 2.6% were Asian), we compared all-cause, cardiovascular, and cancer mortality rates in white, black, Hispanic, and Asian postmenopausal women with and without diabetes. Cox proportional hazard models were used for the comparison from which hazard ratios and 95% confidence intervals were computed. Within each racial/ethnic subgroup, women with diabetes had an approximately 2–3 times higher risk of all-cause, cardiovascular, and cancer mortality than did those without diabetes. However, the hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups. Population attributable risk percentages (PARPs) take into account both the prevalence of diabetes and hazard ratios. For all-cause mortality, whites had the lowest PARP (11.1, 95% confidence interval (CI): 10.1, 12.1), followed by Asians (12.9, 95% CI: 4.7, 20.9), blacks (19.4, 95% CI: 15.0, 23.7), and Hispanics (23.2, 95% CI: 14.8, 31.2). To our knowledge, the present study is the first to show that hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups when stratified by diabetes status. Because of the “amplifying” effect of diabetes prevalence, efforts to reduce racial/ethnic disparities in the rate of death from diabetes should focus on prevention of diabetes. [ABSTRACT FROM PUBLISHER]

The Women on the Move through Activity and Nutrition (WOMAN) study was designed to test whether a nonpharmacological intervention including qualitative and quantitative dietary changes to induce weight loss and increased physical activity levels would reduce blood triglyceride levels and number of low-density lipoprotein particles (LDL-P). Such decreases in lipoproteins and other risk factors could reduce or slow progression of subclinical cardiovascular disease (CVD). Study participants were randomized to either the intervention (Lifestyle Change) or assessment (Health Education) group. Most of the intervention ended at the 30-month visit. The last 48-month examination was completed in 9/2008. There was very substantial weight loss and increased exercise during the first 30 months of the trial resulting in significant decreases in CV risk factors. Most of the intervention effect was lost through 48 months. Weight loss was 3.4 kg in Lifestyle Intervention and 0.2 kg in the Health Education at 48 months (P = 0.000). There were no significant changes at 48 months in lipid levels, blood pressure (BP), glucose, insulin, or in the subclinical measures of coronary calcium, carotid intima media thickness, or plaque. There was a significant decrease in long-distance corridor walk time in the Lifestyle vs. Health Education groups. Significant lifestyle changes can be achieved that result in decreases in CV risk factors. Whether such changes reduce CV outcomes is still untested in clinical trials of weight loss or exercise. Long-term maintenance of successful lifestyle changes, weight loss and reduced risk factors is the hurdle for lifestyle interventions attempting to prevent CV and other chronic diseases. [ABSTRACT FROM AUTHOR]

Arterial diameter is an underutilized indicator of vascular health. We hypothesized that interadventitial and lumen diameter of the common carotid artery would be better indicators of vascular health than carotid plaque or intima media thickness (IMT). Participants were 491 overweight or obese, postmenopausal women who were former or current hormone therapy (HT) users, 52- 62 years, with waist circumference > 80 cm. We evaluated cross-sectional associations of cardiovascular risk factors with carotid measures, by HT status. Former HT users had a worse cardiovascular profile than current HT users: larger adventitial (6.94 mm versus 6.79 mm) and lumen diameter (5.44 mm versus 5.31 mm, both P < 0.01) independent of cardiovascular risk factors; IMT and plaque were similar. Larger diameters were best explained by former HT use, higher pulse pressure, and greater weight. Independent of potential confounders, overweight and obese postmenopausal former HT users had larger carotid diameters than current HT users. Carotid diameter should be considered in studies of HT. [ABSTRACT FROM AUTHOR]

Individuals with 'metabolically benign' obesity (obesity unaccompanied by hypertension, dyslipidemia, and diabetes) are not at elevated 10-year risk of cardiovascular disease (CVD) compared to normal weight individuals. It remains unclear whether these obese individuals or normal weight individuals with clustering of cardiometabolic factors display heightened immune activity. Therefore, we characterized levels of acute-phase reactants (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), white blood cell (WBC) count), adhesion molecules (E-selectin, vascular cell adhesion molecule-1), and coagulation products (fibrinogen, plasminogen activator inhibitor-1 (PAI-1)) among four body size phenotypes (normal weight with 0/1 vs. ≥2 metabolic syndrome components/diabetes and overweight/obesity with 0/1 vs. ≥2 metabolic syndrome components/diabetes) in cross-sectional analyses of 1,889 postmenopausal women from the Women's Health Initiative Observational Study (WHI-OS) nested case-control stroke study. Higher levels of all three inflammatory marker categories were found among women with overweight/obesity or ≥2 metabolic syndrome components or diabetes. Compared to normal weight women with 0 or 1 metabolic syndrome components, normal weight women with ≥2 metabolic syndrome components or diabetes were more likely to have ≥3 inflammatory markers in the top quartile (multivariate odds ratio (OR) 2.0, 95% confidence interval (CI): 1.3-3.0), as were overweight/obese women with 0 or 1 metabolic syndrome components (OR 2.3; 95% CI: 1.5-3.5). Overweight/obese women with ≥2 metabolic syndrome components or diabetes had the highest OR (OR 4.2; 95% CI: 2.9-5.9). Despite findings that metabolically benign obese individuals are not at increased 10-year risk of CVD compared to normal weight individuals, the current results suggest that overweight/obese women without clustering of cardiometabolic risk factors still possess abnormal levels of inflammatory markers. [ABSTRACT FROM AUTHOR]

BackgroundCentral arterial stiffness is increasingly recognized as an important predictor of cardiovascular events and mortality in older adults; however, few studies have evaluated the association of arterial stiffness with mobility decline, a common consequence of vascular disease.MethodsWe analyzed the association of pulse wave velocity (PWV), a measure of aortic stiffness, with longitudinal gait speed over 7 years in 2,172 participants in the Health, Aging and Body Composition (ABC) Study (mean age ± s.d. 73.6 ± 2.9 years, 48% men, 39% black).ResultsIn mixed-effects models adjusted for demographics, each s.d. (396 cm/s) higher PWV was associated with 0.015 (s.e. 0.004) m/s slower gait at baseline and throughout the study period in the full cohort (P < 0.001); this relationship was largely explained by hypertension and other vascular risk factors. Among participants with peripheral arterial disease (PAD) (n = 261; 12.7%), each s.d. higher PWV was independently associated with 0.028 (s.e. 0.010) m/s slower gait speed at baseline and throughout the study period (P < 0.01).ConclusionsThese findings suggest that aortic stiffness may be especially detrimental to mobility in older adults with already compromised arterial function.American Journal of Hypertension (2011). doi:10.1038/ajh.2010.193 [ABSTRACT FROM AUTHOR]

In this report we explore the hypothesis that arterial stiffness indices, which predict cardiovascular disease, might also correlate with microalbuminuria (MA) in type 1 diabetes (T1D), and thus have potential for risk assessment. Three pulse wave analysis (PWA) indices, measured using the SphygmoCor device, were evaluated on 144 participants with childhood-onset T1D. These variables, augmentation index (AIx), augmentation pressure (AP) and subendocardial viability ratio (SEVR, an estimate of myocardial perfusion) (an estimate of myocardial perfusion), were each analysed cross-sectionally in relation to both prevalent MA (defined as albuminuria excretion rate (AER) = 20—199 μg/min) and renal function (assessed by both eGFR and serum cystatin C). AP and SEVR were each univariately associated with AER, estimated glomerular filtration rate (eGFR) and cystatin C. Lower SEVR was also independently related to the presence of MA and degree of albuminuria within normo- and microalbuminuric participants. SEVR, not AP, was independently and negatively associated with both measures of renal function. SEVR is a better predictor of AER than brachial blood pressure measures in those without clinical proteinuria, indicating a potential use for PWA in the early detection of individuals at risk for cardiovascular and renal complications of T1D. [ABSTRACT FROM PUBLISHER]

OBJECTIVE -- To examine the relationship between cardiovascular autonomic neuropathy and pulse waveform analysis (PWA) measures of arterial stiffness in a childhood-onset type 1 diabetes population. RESEARCH DESIGN AND METHODS -- Cardiac autonomic nerve function was measured in the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes by heart rate variability (R-R interval) during deep breathing and expressed as expiration-to-inspiration (E/I) ratio. Other cardiovascular and diabetes factors were also assessed. PWA was performed using SphgymoCor Px on 144 participants at the 18-year follow-up examination. Univariate and multivariate analyses for associations between baseline nerve function and other cardiovascular and diabetes-related factors were performed for augmentation index (AIx), augmentation pressure (AP), and subendocardial viability ratio (SEVR), a surrogate marker of myocardial perfusion. RESULTS -- E/I ratio correlated negatively with both AIx (r = -0.18, P = 0.03) and AP (r = -0.32, P < 0.001) and positively with SEVR (r = 0.47, P < 0.001) univariately. Lower baseline E/I ratio, HDL cholesterol, and a history of smoking were associated with higher follow-up (18 years later) AIx and AP and lower SEVR in multivariate analyses. Higher baseline HbA[sub 1] was also associated with higher AP and lower SEVR multivariately. CONCLUSIONS -- Cardiovascular autonomic neuropathy is associated with increased arterial stiffness measures and decreased estimated myocardial perfusion in those with type 1 diabetes some 18 years later. This association persists after adjustment for potential confounders as well as for baseline HbA[sub 1], HDL cholesterol, and smoking history, which were also associated with these PWA measures. [ABSTRACT FROM AUTHOR]

An objective measure of walking performance could have several potential applications in clinical settings. The cross-sectional relationships among long distance corridor walk (LDCW) time, physical activity, and subclinical cardiovascular disease (CVD) measures were examined before group randomization in 492 participants (mean age, 57.0±2.9 years) from the Women On the Move Through Activity and Nutrition (WOMAN) study, a randomized clinical trial involving postmenopausal women. Longer walk times were significantly associated with higher body mass index (P <0001), average waist circumference (P <0001), and lower levels of physical activity (P <002). The proportion of detectable coronary artery calcification and median aortic pulse wave velocity levels were significantly higher among those with slower walk times (P <002 and P <.001, respectively). Findings from the current report support the utility of the LDCW to identify women at higher risk for CVD who may be candidates for further cardiovascular testing or intensive lifestyle intervention. [ABSTRACT FROM AUTHOR]

Background: Aortic stiffness, assessed using carotid–femoral pulse wave velocity (cfPWV), predicts all-cause and cardiovascular mortality. Brachial–ankle pulse wave velocity index (baPVI) is a newer measure of arterial stiffness obtained using an automated system. Our aim is to evaluate the association between both these measures of arterial stiffness and coronary calcification (CAC), in overweight/obese postmenopausal women, without apparent cardiovascular disease. Methods: The CAC was assessed using electron beam tomography in 504 postmenopausal women, aged 52 to 62 years (88.2% white) with mean body mass index (BMI) 30.8 kg/m2. The CAC scores were analyzed as CAC >0 and CAC >100 versus CAC = 0, or as ln (CAC + 1). Results: The cfPWV was available in 476 women (mean [SD]: 900 (255) cm/sec) and baPVI was available in 441 women (mean [SD]: 1434 (231) cm/sec. Any CAC (CAC >0) was present in approximately 51% of the cohort. Both high cfPWV (RR = 1.5, 1.6, and 1.7 for quartiles 2, 3, and 4 v 1) and baPVI (RR = 2.9, 3.7. and 4.0 for quartiles 2, 3, and 4 v 1) were associated with the presence of calcification (CAC >0). The association was attenuated but remained significant only for baPVI after adjusting for age, systolic blood pressure, average waist circumference, BMI, fasting glucose, insulin, lipids, hormone replacement therapy, and smoking status. High odds of severe calcification (CAC >100) was seen with the highest quartile of the cfPWV (RR = 5.3) and baPVI (RR = 7.8), and these associations remained significant in multivariable analysis. Conclusions: Both cfPWV and baPVI are associated with presence and severity of coronary calcification in overweight postmenopausal women. [Copyright &y& Elsevier]

Background: Individuals of low socioeconomic status (SES) are at increased risk for cardiovascular disease relative to persons of more advantaged social position. Recent evidence suggests that community SES (variation in the material and social resources of communities) also predicts incident cardiovascular disease, and may do so independently of individual level SES. In this study we examined whether community SES is similarly associated with preclinical vascular disease, as measured by carotid artery ultrasonography. Methods: Subjects were 230 untreated hypertensive men without history of coronary heart disease, residing in and around Pittsburgh, PA (80% white, 20% African-American; mean age, 56 years). Community SES was defined by levels of income, economic disadvantage (eg, poverty, unemployment), housing costs, and educational attainment in the US Census tract of residence for each subject. A composite community SES score was calculated for each subject as the average of all extracted census measures. Individual SES was estimated from subjects’ years of education and current annual income. Results: Regression analyses accounting for traditional risk factors showed community disadvantage to be associated with greater intima–medial thickness (b = 0.02, P < .05) and plaque occurrence (odds ratio [OR] = 1.51, P < .01). The latter association persisted on multivariable adjustment for both risk factors and individual markers of social position (SES) (OR = 1.68, P < .01). Conclusions: Irrespective of one’s own income or educational attainment, untreated hypertensive men living in poorer communities are more likely to exhibit preclinical atherosclerosis than residents of more affluent areas. [Copyright &y& Elsevier]

Background The Women’s Health Initiative (WHI) clinical trial found no reduction in coronary heart disease events among hormone therapy (HT) users despite an improvement in lipid levels. We hypothesized that a lack of benefit of HT on atherosclerosis would be better explained by the lipoprotein subclasses than by standard lipid levels. To test this hypothesis, we evaluated differences in coronary calcification, lipids, and lipoprotein subclasses among HT users and nonusers in a longitudinal study of the menopause. Methods Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary artery calcification (CAC) determined by electron beam computed tomography were compared between HT users (49%) and nonusers among 243 women, approximately 8 years postmenopausal, from the Healthy Women Study. Results The distribution of CAC scores was not significantly different between HT users and nonusers. As expected, HT users had higher levels of large high-density lipoprotein (HDL) particles and large very low-density lipoprotein (VLDL) particles. However, despite lower low-density lipoprotein (LDL) cholesterol levels among HT users, there were no significant differences between HT users and nonusers in any LDL subclass measures, including particle size or concentration. Regardless of HT use, women with CAC had higher levels of large VLDL and small LDL particles, higher LDL particle concentration, and smaller mean LDL size compared with women with no detectable CAC. Conclusions Compared with nonusers, HT users had higher levels of VLDL particles (triglycerides) and did not have a better LDL subclass distribution, which may explain the failure of HT to be associated with a difference in CAC in our study or with a reduction in coronary heart disease risk in randomized clinical trials. [ABSTRACT FROM AUTHOR]

: Background:Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals.: Methods:Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998.: Results:Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993.: Conclusions:In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima–media thickness, heart rate, and decreased physical activity measured several years earlier. [Copyright &y& Elsevier]