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We describe a first suspected case of fibrosing mediastinitis following anti-programmed death (PD)-1 therapy, pembrolizumab. Multimodality imaging, including cardiac magnetic resonance imaging, and a multidisciplinary team approach were integral to the diagnosis. If further substantiated, systematic surveillance after anti-PD-1 therapy for fibrosing mediastinitis may be warranted. (

Background: Provider and system level barriers can delay timely initiation of statin therapy in primary atherosclerotic cardiovascular disease (ASCVD) prevention. A simple, pragmatic and scalable quality improvement (QI) approach is needed to address these gaps. Methods: We describe methods and preliminary results of a QI initiative in a resident run internal medicine clinic in Cayuga Medical Center (total 19 residents, 5 attendings, ~200 patients seen/month with 10% no shows). First, we assessed rates of lipids tested and statin use in 40-75 years old patients without ASCVD. Second, we performed a focus group discussion (FGD) among residents, attendings and clinic leadership to understand barriers for statin use. Third, we outlined key actionable items informed by FGD. Finally, we will assess the impact of the intervention. Findings: We report baseline data in 325 consecutive patients (Table). Mean age was 55.2 years (50.2% women), 50.6% did not have lipids checked and only 17.5% were on statin therapy in the preceding 3 years. Three major themes from FGD were: lack of automated ASCVD score reporting in electronic medical record (EMR), insufficient clinic time and follow up visits. Subsequently, we adopted automated ASCVD risk reporting in EMR and telemedicine follow up to address identified gaps and associated downstream impact, which is currently ongoing. Conclusion: Using mixed-method approach, we describe an implementation strategy to address gaps in cholesterol management in primary prevention patients in a resident run clinic. If effective, this strategy can be a model for other clinics.

Introduction: Bhutanese refugees have a higher prevalence of type 2 diabetes but are less likely to achieve medication adherence and glycemic control. The purpose of this project was to understand factors affecting diabetes medication adherence in this population. Methodology: This was a qualitative project using focus groups of adult Bhutanese refugees with type 2 diabetes ≥18 years old and hemoglobin A1C ≥8% and their caregivers from a family medicine clinic at the University of Kansas. Data were analyzed using content analysis. Results: A total of 23 individuals participated. Three themes emerged from data analysis: desire to engage in care but face multiple barriers, family and community support invaluable for health, and considerations for culturally contextual person-centered care. Participants provided specific recommendations to address the barriers, with emphasis on improving health literacy. Discussion: Integrating the identified factors can foster person-centered, culturally congruent care to improve diabetes medication adherence in Bhutanese refugees.

OBJECTIVES Cardiac troponin T, measured using a high-sensitive assay (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well-designed prospective studies with extended follow-up have been conducted. We aimed to estimate the association of hs-cTnT and NT-proBNP with 15-year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study. DESIGN Prospective cohort study. SETTING Four US communities. PARTICIPANTS A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively. MEASUREMENTS We examined association of hs-cTnT and NT-proBNP with 15-year change (1996-1998 to 2011-2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs-cTnT and NT-proBNP into a three-level categorical variable. RESULTS At baseline (1996-1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs-cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT-proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (-.34; 95% confidence interval = -.63 to -.04). CONCLUSION Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future. J Am Geriatr Soc 67:2353-2361, 2019.

Objectives This study sought to assess periprocedural bleeding complications in lower-extremity peripheral vascular interventions (PVIs). Background Few studies have examined the incidence, predictors, or outcomes of periprocedural bleeding after lower-extremity PVI. Methods The study examined patients undergoing PVI at 76 hospitals in the National Cardiovascular Data Registry PVI registry from 2014 to 2016. Post-PVI major bleeding was defined as any overt bleeding with a hemoglobin (Hb) drop of ≥3 g/dl, any Hb decline of ≥4 g/dl, or blood transfusion in patients with pre-procedure Hb >8 g/dl within 72 h of their procedure. Hierarchical multivariable logistic regression was used to identify factors independently associated with post-PVI bleeding. The study also examined adjusted in-hospital mortality among patients with or without major bleeding complications. Results Among 18,289 PVI procedures, major bleeding occurred in 744 (4.10%). Patient characteristics independently associated with bleeding included age, female sex, heart failure, pre-procedural hemoglobin Conclusions Major bleeding occurred in 4.10% of lower-extremity PVI procedures and was associated with several patient and procedural characteristics, as well as in-hospital mortality. These insights can be incorporated into strategies to reduce periprocedural bleeding after PVI.

This paper aims to explore the burgeoning burden of cardiovascular and metabolic disease (CMD) risk factors among South Asian labor migrants to the Middle East. We conducted a qualitative synthesis of literature using PubMed/Medline and grey literature searches, supplemented by a policy review of policies from the South Asian countries. We found a high burden of cardio-metabolic risk factors among the migrants as well as among the populations in the home and the host countries. For example, two studies reported the prevalence of diabetes mellitus (DM) ranging between 9 and 17% among South Asian migrants. Overweight and obesity were highly prevalent amongst South Asian male migrants; prevalence ranged from 30 to 66% (overweight) and 17–80% (obesity) respectively. The home country population had a significant CMD risk factor burden. Nearly 14 to 40% have three or more risk factors: such as hypertension (17 to 37%), diabetes (3 to 7%), overweight (18 to 41%), and obesity (2 to 15%). The host country also exhibited similar burden of risk factors: hypertension (13 to 38%), diabetes (8 to 17%), overweight (33 to 77%) and obesity (35 to 41%). Only Nepal, Bangladesh and Sri Lanka have some provisions related to screening of CMDs before labor migration. Further, analysis of policy papers showed that none of the reviewed documents had requirements for screening of any specific CMDs, but chronic diseases were used generically, failing to specify specific screening target. Given the high burden of risk factors, migrants’ health should become an urgent priority. The lack of specific focus on screening during different stages of labor migration should receive attention. The International Labour Organization and the International Office for Migration, through their country coordination teams should engage local stakeholders to create policies and plans to address this concern. Similarly, there is a need for the host country to become an equal partner in these efforts, as migrant’s better cardiometabolic health is in the benefit of both host and home countries. Electronic supplementary material The online version of this article (10.1186/s12992-019-0468-8) contains supplementary material, which is available to authorized users.

ObjectiveTo examine the association of specific lipoproteins/inflammatory enzyme with cognitive change.MethodsWe examined the association of apolipoprotein B (ApoB), small-dense low-density lipoprotein cholesterol (sdLDL-C), lipoprotein (a) (Lp[a]), and lipoprotein-associated phospholipase A2 (LpPLA2) activity with 15-year change in Delayed Word Recall Test, Digit Symbol Substitution Test (DSST), Word Fluency Test (WFT), and overall summary score in 9,350 participants in the Atherosclerosis Risk in Communities study. We assessed interaction by race, sex, education, APOE ε4 status, and statin use. We also addressed questions of informative missingness, the role of stroke, and the influence of fasting status.ResultsThe mean (SD) age was 63.4 (5.7) years; 56.4% were women and 17.4% were black. We observed faster cognitive decline on DSST and global z scores with every 10-mg/dL higher sdLDL-C level (Δ DSST z score, −0.010; 95% confidence interval [CI] −0.017, −0.002 and Δ global z score, −0.011; −0.021, −0.001) and the highest vs the lowest ApoB quintiles (Δ DSST z score, −0.092; −0.0164, −0.019 and Δ global z score, −0.101; −0.200, −0.002). Association for the ApoB quintiles with Δ global z score (−0.10) was comparable with that of having 1 APOE ε4 allele (−0.11). Higher Lp(a) was associated with slower decline in DSST, WFT, and global z scores. LpPLA2 activity was not associated with cognitive change. Results were similar in sensitivity analyses. The associations of sdLDL-C or Lp(a) on cognitive change were more pronounced in statin users.ConclusionsOptimal control of atherogenic lipoproteins such as ApoB and sdLDL-C in midlife for cardiovascular health may also benefit late-life cognitive health.

Introduction: Elevated resting heart rate (RHR) has been shown to be associated with both all-cause and cardiovascular mortality. Prior studies have provided conflicting estimates of the strength of each association. To explore the relationship between RHR and competing mortality risks, we sought to compare the association between RHR and cardiovascular and non-cardiovascular mortality among participants in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods: Eligible SPRINT participants had baseline RHR, longitudinal follow-up, and were not using beta blockers or non-dihydropyridine calcium channel blockers. Mortality was classified by a treatment-blinded adjudication committee as cardiovascular if secondary to coronary heart disease, stroke, sudden cardiac death, or congestive heart failure. Multivariable Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for cardiovascular and non-cardiovascular mortality, separately, associated with a 10 beats per minute increase in RHR. Results: Among 5,571 eligible SPRINT participants (67.1 ± 9.4 years, 33.8% female, 63.8% white, mean RHR 70.4±11.8 beats per minute) over a median 3.8 years of follow-up, there were 56 cardiovascular deaths and 176 non-cardiovascular deaths. In models adjusted for age, sex, race, prior cardiovascular disease, smoking, systolic blood pressure, creatinine, total cholesterol, high-density lipoprotein cholesterol, and trial treatment assignment, higher RHR (per ten beat-per-minute increase) was associated with both cardiovascular (HR 1.17, 95% CI 1.02-1.35) and non-cardiovascular mortality (HR 1.27, 95% CI 1.13-1.43). Conclusions: Elevated RHR was associated with both cardiovascular and non-cardiovascular mortality, suggesting that RHR may serve as a marker of both global health rather and cardiovascular health. Higher RHR may reflect imbalance in autonomic tone and further studies are needed to explore the mechanisms of these associations.4

May Measurement Month (MMM) is a global initiative to screen high blood pressure (BP) in the community and increase awareness at the population level. High BP is the leading risk factor for mortality worldwide and in Nepal. This study presents the results of the 2019 MMM in Nepal. Opportunistic BP screening was conducted in 30 out of 77 districts across Nepal and aged ≥18 years at the community and public places. BP was measured three times in a seated position. A total of 74 205 individuals participated in the study, mean age 39.9 years, and 58% were male. BP measurements for the second and third readings were available for 69 292 (93.3%) individuals. The proportion of the population that were hypertensive was 27.5% (n = 20 429). Among those hypertensives, 46.3% were aware of their hypertensive status and of these, 37.5% were on antihypertensive medication. Only 54.3% of those on antihypertensive medication had their BP controlled. Of the community screened, those self reporting to have diabetes, current tobacco users, and current alcohol drinkers were 6.7%, 23.6%, and 31.9%, respectively; 20.6% of the participants were overweight, and 6.5% were obese. Since the first BP screening campaign, MMM 2017 in Nepal, the number of participants screened has largely increased over the years. MMM’s success in Nepal is through a coordinated mobilization of trained health science students and volunteers in the communities. The Nepal MMM data demonstrates that large community-based BP screening campaigns are possible in low resource settings.

Objective: Hypertension is a leading risk factor of global deaths. May Measurement Month (MMM) is an initiative of the International Society of Hypertension (ISH) to raise awareness of the importance of measuring blood pressure. Nepal has been participating in the MMM campaign since 2017. This study presents the initial results of the 2019 MMM in Nepal.Design and method: An opportunistic cross-sectional survey of volunteers aged at least 18 years was carried out in May 2019. Data were collected from 30 out of 77 districts using a structured questionnaire developed by ISH; adapted in the local language and context. Screenings were conducted in health facilities and public places using either digital or manual sphygmomanometers. Trained volunteers were mobilized to take part in the screening. Ethical approval for the study was obtained from the Nepal Health Research Council.Results: The mean age of the participants was 39.4 ± 15.2 years, and 58% of them were female. A total of 72,320 individuals were screened, out of which the mean of the 2nd and 3rd readings was available for 66,955 {93%} individuals. The proportions of self-reported diabetes, current tobacco user and current alcohol drinkers were 6%, 24% and 22%, respectively. Likewise, 27% of the participants were overweight, and 12% were obese. The mean systolic blood pressure was 119 ± 14 mm Hg, and the mean diastolic blood pressure were 80 ± 11 mm Hg. A third of the participants {32%} were screened for blood pressure for the first time in the last one year. The proportion of hypertension was 24% {n = 15,872} with more hypertensive male {28%} than female {18%}. Among individuals with hypertension, 47% {7,507} were receiving treatment and among those under treatment, 19% {1,226} had uncontrolled blood pressure.Conclusions: These blood pressure screening results suggest a higher proportion of hypertensive patients were not on treatment and only a fifth of those under treatment achieved blood pressure control in Nepal. Screening campaign such as MMM with mobilization of volunteers can be an important approach for identifying undetected or uncontrolled cases of hypertension in low resource settings like Nepal.

Individuals with Familial Hypercholesterolemia (FH) are at high risk for atherosclerotic cardiovascular disease (ASCVD) events.The purpose of this study was to evaluate the incidence, predictors, and outcomes of admissions for acute coronary syndromes (ACS) in this high-risk group.Utilizing the National Readmission Databases, we identified individuals with or without FH admitted to participating hospitals for ACS. The primary outcome was admission for recurrent ACS at 11 month follow-up.There were a total of 1,697,513 ACS admissions from 10/2016 to 12/2017 (non-FH=1,696,979 and FH=534). Individuals with FH admitted for ACS were younger (median age 57 vs 69 y), had fewer comorbidities (hypertension 74.7% vs 79.6%; diabetes mellitus 30.5% vs 39.0%;p0.01), were more likely to present with ST-elevation-myocardial infarction (32.8% vs 22.6%;p0.01) and more likely to undergo multivessel percutaneous coronary intervention (11.4% vs 7.6%;p0.01) than patients without FH. After propensity-score matching, FH patients more commonly experienced in-hospital VT arrest (11.8% vs 8.0%;p0.01) and required more mechanical circulatory support (8.6% vs 3.3%; p0.01). The 30-day readmission in those with FH was more frequently for cardiovascular disease (81.5% vs 46.5%; =p0.01). At 11-month follow-up, FH patients were more likely to be readmitted with recurrent ACS compared to those without FH (hazard ratio=2.34; 95% confidence interval=1.30-4.23; p0.01).Individuals with FH admitted for ACS are younger, have fewer comorbidities, and more frequently present with STEMIs compared to those without FH. FH patients were more likely to suffer in-hospital cardiac complications and have a higher incidence of recurrent ACS.

Background Noncommunicable diseases (NCDs) are the leading causes of deaths globally. Currently, there are limited high-quality data on the epidemiology and usefulness of community-based screening and treatment of NCDs in low-to-middle-income countries (LMIC), like Nepal. We describe the protocol of a community-based, longitudinal epidemiological study of screening and management of NCDs in rural Nepal. Methods We organize monthly mobile health clinics to screen NCDs among 40- to 75-year-old residents from municipal subdivision wards 3, 4, 6, and 7 of Ghorahi submetropolitan city, Dang, Nepal (approximately 406 km west of the capital, Kathmandu). We estimate a total of 7052 eligible participants. After obtaining informed consent, trained personnel will collect sociodemographic and lifestyle data, medical, medication, and family history using validated questionnaires, plus anthropometric measures and capillary glucose levels. We will screen for hypertension, diabetes, obesity, dyslipidemia, tobacco and alcohol use, self-reported physical activity, dietary habits, cardiovascular disease, stroke, chronic lung disease, cancer, and chronic kidney disease. We will also check hemoglobin A1C, lipid panel, serum creatinine, sodium, potassium, urine dipstick, and urine albumin-to-creatinine ratio in high-risk participants. We will offer lifestyle counseling, pharmacotherapy or refer to higher level care, where appropriate; routinely follow participants with NCDs for continuity of care; and follow individuals without NCDs but with elevated glucose, prehypertension or other risk factors every year, and those without risk factors every 2 years. We will monitor participants in the community to reduce attrition and to track all-cause and disease-specific mortality. Discussion Understanding the community burden of NCDs in resource-limited setting and testing effectiveness of community-based screening and management of NCDs will provide insights to develop national policy to address NCD burden in LMIC like Nepal.

Background The burgeoning rise of non-communicable diseases (NCDs) is posing serious challenges in resource constrained health facilities of Nepal. The main objective of this study was to assess the readiness of health facilities for cardiovascular diseases (CVDs), diabetes and chronic respiratory diseases (CRDs) services in Nepal. Methods This study utilized data from the Nepal Health Facility Survey 2015. General readiness of 940 health facilities along with disease specific readiness for CVDs, diabetes, and CRDs were assessed using the Service Availability and Readiness Assessment manual of the World Health Organization. Health facilities were categorized into public and private facilities. Results Out of a total of 940 health facilities assessed, private facilities showed higher availability of items of general service readiness except for standard precautions for infection prevention, compared to public facilities. The multivariable adjusted regression coefficients for CVDs (β = 2.87, 95%CI: 2.42–3.39), diabetes (β =3.02, 95%CI: 2.03–4.49), and CRDs (β = 15.95, 95%CI: 4.61–55.13) at private facilities were higher than the public facilities. Health facilities located in the hills had a higher readiness index for CVDs (β = 1.99, 95%CI: 1.02–1.39). Service readiness for CVDs (β = 1.13, 95%CI: 1.04–1.23) and diabetes (β = 1.78, 95%CI: 1.23–2.59) were higher in the urban municipalities than in rural municipalities. Finally, disease-related services readiness index was sub-optimal with some degree of variation at the province level in Nepal. Compared to province 1, province 2 (β = 0.83, 95%CI: 0.73–0.95) had lower, and province 4 (β =1.24, 95%CI: 1.07–1.43) and province 5 (β =1.17, 95%CI: 1.02–1.34) had higher readiness index for CVDs. Conclusion This study found sub-optimal readiness of services related to three NCDs at the public facilities in Nepal. Compared to public facilities, private facilities showed higher readiness scores for CVDs, diabetes, and CRDs. There is an urgent need for policy reform to improve the health services for NCDs, particularly in public facilities.

High salt (sodium chloride) intake raises blood pressure and increases the risk of developing hypertension, a major risk factor for cardiovascular disease. Little is known about salt intake in Nepal, and no study has estimated salt consumption from 24-hour urinary sodium excretion. Participants (n = 451) were recruited from the Community-Based Management of Non-Communicable Diseases in Nepal (COBIN) cohort in 2018. Salt intake was estimated by analyzing 24-hour urinary sodium excretion. Multivariate linear regression was used to estimate differences in salt intake. The mean (±SD) age and salt intake were 49.6 (±9.8) years and 13.3 (±4.7) g/person/d, respectively. Higher salt intake was significantly associated with male gender (β for female = −2.4; 95% CI: −3.3, −1.4) and younger age (β10 years = −1.4; 95% CI: −1.4, −0.5) and higher BMI (β = 0.1; 95% CI: 0.0, 0.2). A significant association was also found between increase in systolic blood pressure and higher salt intake (β = 0.3; 95% CI: 0.0, 0.7). While 55% reported that they consumed just the right amount of salt, 98% were consuming more than the WHO recommended salt amount (

Supplemental material, GAM917379 Supplemental Material5 for Study, Design, and Rationale of Noncommunicable Diseases in Nepal (NCD Nepal) Study: A Community-Based Prospective Epidemiological and Implementation Study in Rural Nepal by Gagan Neupane MBBS, Sameer Acharya MBBS, Manoj Bhattarai MD, Ashish Upadhyay MD, Bishal Belbase MBBS, Manoj Bhandari MD, Drona Pandeya MS, MLS (ASCP), CM, Shatakshi Pokharel MBBS, Sulochana Ghimire PCL, BPH, Gorakh Thapa PCL, Biraj Karmacharya MPH, PhD, Madan Raj Bhatt MA, MPH, John A Spertus MD, MPH, Dinesh Neupane MSPH, PhD, Lava Timsina MPH, PhD, Yashashwi Pokharel MD, MSCR, in Global Advances in Health and Medicine

Additional file 1: Supplementary table 1. Description of each domain (general readiness, cardiovascular diseases readiness, diabetes service readiness, and chronic respiratory diseases readiness).

Background The ACC/AHA cholesterol guidelines recommend patients with peripheral artery disease (PAD) be treated with a moderate to high-intensity statin. The extent to which patients with new or worsening PAD symptoms are offered guideline therapy is unknown. Hypothesis There is significant variability in rate of guideline-directed statin intensification across clinical practices. Methods In the PORTRAIT registry, patterns of statin therapy were assessed in 1144 patients at 16 PAD specialty clinics between June 2011 and December 2015 before and after an evaluation for new or worsening claudication symptoms. We documented whether patients were treated with a guideline statin as well as the incidence of statin intensification. Statin intensification was defined as transitioning from no statin or low-intensity statin to moderate or high-intensity statin treatment. Patient factors associated with intensification were examined. Site and provider-level variation in intensification was summarized using an adjusted median odds ratio (aMOR). Results Among 1144 patients, 810 (70.8%) were initially on guideline therapy compared to 334 (29.2%) that were not. In the latter, 103 (30.8%) received intensification following evaluation. Patients with typical symptoms displayed greater odds of intensification (OR 3.74; 95% CI: 1.23-11.41) while older patients had lower odds of intensification (OR 0.60/decade; 95% CI: 0.41-0.88). Site variability for statin intensification was observed across sites (aMOR = 3.15; 95% CI 1.22-9.60, [P = 0.02]) but not providers (aMOR = 1.89; 95% CI 1.00-3.90, [P = 0.14]). Conclusions Most patients evaluated at a PAD specialty clinic for new or worsening claudication symptoms arrived on guideline statin therapy. Only 31% not receiving appropriate therapy underwent statin intensification. These findings highlight an important opportunity to optimize medical therapy for patients with PAD.

While high-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation and higher cardiovascular risk, its association with health status (symptoms, function and quality of life) after acute myocardial infarction (AMI) is unknown.Among 3410 patients with AMI from the TRIUMPH (N = 1301) and VIRGO (N = 2109) studies, we compared 1-year generic (Medical Outcome Study Short Form-12 and Euro Quality of Life Visual Analog Scale) and disease-specific (Seattle Angina Questionnaire) health status outcomes in those with hs-CRP ≥2 mg/L vs.2 mg/L. In hierarchical linear regression models, we examined the association of 30-day hs-CRP levels with 1-year health status without adjustment, after adjusting for 30-day health status, and after adjusting for demographic, socioeconomic, disease severity/comorbidities and treatment characteristics.The median (25th, 75th percentiles) 30-day hs-CRP was 2.6 (1.1, 6.1) mg/L and 59% had hs-CRP ≥2 mg/L. Statin therapy was used in 92% of patients at hospital discharge. Thirty-day hs-CRP ≥2 mg/L was inversely associated with all 1-year health status measures in unadjusted and partially adjusted models, but not in fully-adjusted models. Results were similar when hs-CRP was analyzed as a continuous variable.While elevated hs-CRP 30 days after AMI was associated with worse health status in unadjusted analyses, this was not significant after adjusting for comorbidities, suggesting that hs-CRP may be a marker of comorbidities associated with worse health status. Whether reducing inflammation in AMI patients will improve health status should be tested in ongoing trials.

Introduction Existing studies predominantly consider the association of late-life lipid levels and subsequent cognitive change. However, midlife rather than late-life risk factors are often most relevant to cognitive health. Methods We quantified the association between measured serum lipids in midlife and subsequent 20-year change in performance on three cognitive tests in 13,997 participants of the Atherosclerosis Risk in Communities study. Results Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides were associated with greater 20-year decline on a test of executive function, sustained attention, and processing speed. Higher total cholesterol and triglycerides were also associated with greater 20-year decline in memory scores and a measure summarizing performance on all three tests. High-density lipoprotein cholesterol was not associated with cognitive change. Results were materially unchanged in sensitivity analyses addressing informative missingness. Discussion Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides in midlife were associated with greater 20-year cognitive decline.

Objectives This study sought to determine whether pre-heart failure (HF) myocardial injury explains the differential mortality after HF across weight categories. Background Obesity is a risk factor for HF, but pre-HF obesity is associated with lower mortality after incident HF. High-sensitivity cardiac troponin T (hs-cTnT) is a sensitive marker of myocardial injury, and predicts incident HF and mortality. Methods Stratifying 1,279 individuals with incident HF hospitalizations by their pre-HF hs-cTnT levels ( Results Mean age at HF was 74 years (53% women, 27% black). Individuals with pre-HF hs-cTnT ≥14 ng/l had higher mortality after incident HF (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.18 to 1.80) compared to individuals with hs-cTnT Conclusion Although greater pre-existing subclinical myocardial injury was associated with higher mortality after incident HF hospitalization, it did not explain the obesity paradox in HF, which was observed irrespective of subclinical myocardial injury. (Atherosclerosis Risk In Communities [ARIC]; NCT00005131 )

Documents reviewed for panel 1 are listed here. (DOCX 17 kb)

Terms used for searches in Pubmed/Medline are listed here. (DOCX 19 kb)

Background: Obesity is a growing epidemic that has been linked to the development of cardiovascular disease (CVD). Guideline-directed medications for secondary prevention and risk factor control are recommended for patients with all forms of CVD. The association of body mass index (BMI) with use of medications for secondary prevention and risk factor control in patients with CVD are poorly understood. Methods and Results: We identified 1 122 567 patients with CVD receiving care in 130 Veterans Affairs facilities from October 1, 2013, to September 30, 2014. Five groups were stratified by BMI—underweight (BMI, 2 ), normal (BMI, 18.5–24.9 kg/m 2 ), overweight (BMI, 25–29.9 kg/m 2 ), obese (BMI, 30–39.9 kg/m 2 ), and extremely obese (BMI, ≥40 kg/m 2 ). A composite of 4 measures—blood pressure Conclusions: OMT was low in the entire cohort. There is an inverse U-shaped relationship between OMT and BMI with patients who are underweight and extremely obese less likely to receive OMT compared with patients with normal BMI.

Summary of policy analysis in South Asia region are listed here. (DOCX 17 kb)

Cardiovascular disease (CVD) is a systemic process involving multiple vascular beds and includes coronary heart disease (CHD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD). All these manifestations are associated with an increased risk of subsequent myocardial infarction, stroke, and death. Guideline-directed medical therapy is recommended for all patients with CVD. In a cohort of US veterans, we identified 1,242,015 patients with CVD receiving care in 130 Veterans Affairs facilities from October 1, 2013 to September 30, 2014. CVD included diagnoses of CHD, PAD, or ICVD. We assessed the frequency of risk factor optimization and the use of guideline-directed medical therapy in patients with CHD, PAD alone, ICVD alone, and PAD + ICVD groups. A composite of 4 measures (blood pressure140/90 mm Hg, A1c7% in diabetics, statin use, and antiplatelet use in eligible patients), termed optimal medical therapy (OMT) was compared among groups. Multivariate logistic regression was performed with CHD as the referent category. CHD comprised 989,380 (79.7%), PAD alone 70,404 (5.7%), ICVD alone 163,730 (13.2%), and PAD + ICVD 18,501 (1.5%) of the cohort. Overall, only 36% received OMT with adjusted odds ratios of 0.54 (95% CI 0.53 to 0.55), 0.77 (0.76 to 0.78), and 0.97 (0.94 to 1.00) for patients with PAD alone, ICVD alone, and PAD + ICVD, respectively, compared with patients with CHD. In conclusion, OMT was low in all groups. Patients with PAD alone and ICVD alone were less likely to receive OMT than those with CHD and PAD + ICVD.

A clinician has a large number of guidelines to follow. Searching the words "cardiovascular" and "guideline" on the website, www.guideline.gov yielded 502 cardiovascular guidelines, 40 alone in 2015. 1 [National Guideline Clearinghouse: Agency for Healthcare Research and 19 Quality (n.d.)] Similarly, searching the words "cholesterol" and "guideline" yielded 107 results, 6 alone in 2015. This information overload can decrease providers' self-efficacy in using guidelines, particularly if they have inconsistent messages. Moreover, a busy provider can easily be lost if the emphasis is on highlighting differences rather than similarities on the same topic. There are several guidelines for management of blood cholesterol and lipids. Despite being more similar than different, their similarities have not received as much attention as the differences between them. Unfortunately, there are still major gaps in current clinical practice even across these common themes. In this review, we will provide a brief overview of various cholesterol/lipid guidelines followed by a discussion of the differences but more importantly, similarities between them.

Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation.

Background Limited data are available to assess whether access to and quality of cardiovascular disease (CVD) care are comparable among men and women in India. We analyzed data from the American College of Cardiology's PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP) to evaluate gender disparities in CVD care delivery. Methods and results Between 2011 and 2015, we collected data on performance measures for patients with coronary artery disease (CAD) (n=14,010), heart failure (HF) (n=11,965) and atrial fibrillation (AF) (n=496) in PIQIP, among 17 participating practices. The total number of women was 31,796 (32.0%). Women had fewer total encounters compared to men during the study interval (mean number of encounters=2.59 vs. 2.82 for women and men, respectively, p≤0.001). Women were significantly younger (48.9years vs. 51.5years, p≤0.01), but had a higher co-morbidity burden compared to men — hypertension (62.0% vs. 45.6%, p≤0.01), diabetes (39.4% vs. 35%, p≤0.01), and hyperlipidemia (3.7% vs. 3.1%, p=0.19). On the contrary, the guideline-directed medication prescriptions were strikingly lower in women with CAD compared to men — aspirin (38% vs. 50.4%, p≤0.001), aspirin or thienopyridine combination (46.9% vs. 57.2%, p≤0.001), and beta-blockers (36.8% vs. 47.8%, p≤0.001). Similarly, among women with ejection fraction ≤40%, the use of guideline-directed medical therapy was significantly lower compared to men for beta-blockers (30.8% vs. 37.0%, p≤0.001), angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin receptor blockers (ARBs) (29.3% vs. 34.9%, p≤0.001), and beta-blockers/ACE-i or ARBs (24.6% vs. 31.0%, p≤0.001). Among patients with atrial fibrillation and CHADS2 score≥2, more women were on oral anticoagulation (19.6% vs. 14.6%, p=0.34), although this was not significantly different, and the overall number of patients with atrial fibrillation was low. Conclusions Despite a significantly higher co-morbidity burden in women, we found fewer women receiving guideline-directed medical therapy for CVD compared with men. If such disparities are confirmed in the larger Indian population, it is important to find potential causes for, and seek solutions to narrow this gap.

We sought to determine use of any and at least moderate-intensity statin therapy in a national sample of patients with diabetes mellitus (DM), with the hypothesis that nationwide frequency and facility-level variation in statin therapy are suboptimal. We sampled patients with DM age 40 to 75 years receiving primary care between October 1, 2012, and September 30, 2013, at 130 parent facilities and associated community-based outpatient clinics in the Veterans Affairs Health Care System. We examined frequency and facility-level variation in use of any or at least moderate-intensity statin therapy (mean daily dose associated with ≥30% low-density lipoprotein cholesterol lowering). In 911 444 patients with DM, 68.3% and 58.4% were receiving any and moderate- to high-intensity statin therapy, respectively. Patients receiving statin had higher burden of cardiovascular disease, were more likely to be on nonstatin lipid-lowering therapy and to receive care at a teaching facility, and had more frequent primary-care visits. Median facility-level uses of any and at least moderate-intensity statin therapy were 68.7% (interquartile range, 65.9%-70.8%) and 58.6% (interquartile range, 55.8%-61.4%), respectively. After adjusting for several patient-related and some facility-related characteristics, the median rate ratios for any and moderate- to high-intensity statin therapy were 1.20 (95% confidence interval: 1.18-1.22) and 1.29 (95% confidence interval: 1.24-1.33) respectively, indicating 20% to 29% variation in statin use between 2 identical patients receiving care at 2 random facilities. Statin use was suboptimal in a national sample of patients with DM with modest facility-level variation, likely indicating differences in statin-prescribing patterns.

Little is known about the use of guideline-directed medical therapy (GDMT) in outpatients with heart failure with reduced left ventricular ejection fraction (HFrEF; ≤40%) in India. Our objective was to understand the use of GDMT in outpatients with HFrEF in India. The Practice Innovation And Clinical Excellence (PINNACLE) India Quality Improvement Program (PIQIP) is a registry for cardiovascular quality improvement in India supported by the American College of Cardiology Foundation. Between January 2008 and September 2014, we evaluated documentation of use of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and β-blockers, or both, among outpatients with HFrEF seeking care in 10 centers enrolled in the PIQIP registry. Among 75 639 patients in the PIQIP registry, 34 995 had EF reported, and 15 870 had an EF ≤40%. The mean age was 56 years; 23% were female. Hypertension, diabetes, coronary artery disease, and myocardial infarction were present in 37%, 23%, 27%, and 17%, respectively. Use of ACEIs/ARBs, β-blockers, and both were documented in 33.5%, 34.9%, and 29.6% of patients, respectively. The documentation of GDMT was higher in men, in patients age ≥65 years, and in those with presence of hypertension, diabetes, or coronary artery disease. Documentation of GDMT gradually increased over the study period. Among patients enrolled in the PIQIP registry, about two-thirds of patients with EF ≤40% did not have documented receipt of GDMT. This study is an initial step toward improving adherence to GDMT in India and highlights the feasibility of examining quality of care in HFrEF in a resource-limited setting.

Improving symptoms, functions, and quality-of-life (ie, health status) is one of the important goals in treatment of patients with peripheral artery disease (PAD).1 However, it is unknown whether health status responses differ by race (black versus white) with alternative PAD treatment modalities. Such differences may exist given the disproportionate burden of PAD in minority populations, and rapid disease progression as compared with white,2 as well as differences in psychosocial and economic factors and possibly differences in exercise level, which is known to improve outcomes in patients with PAD.3,4 Understanding whether black and white respond differently to treatments can help us better support targeted therapy to improve quality of care. This is relevant because until now, supervised exercise (SE) programs for PAD were not available in the United States, and recently, the Centers for Medicare and Medicaid Services agreed to reimburse for SE therapy.5 If there is heterogeneity in response to SE, knowing this difference is important to provide patient-centered care and to get maximum treatment benefit for each unique patient population. The CLEVER trial (Claudication: Exercise Versus Endoluminal Revascularization) randomized patients with claudication from aortoiliac disease to SE, stent therapy (ST), or optimal medical care (OMC). Short-term results indicated superior treadmill walking performance (ie, peak walking time and claudication onset time) with SE than either ST or OMC. Conversely, benefit in PAD-specific health status (Peripheral Artery Questionnaire [PAQ] summary score)6 was more favorable for ST than either SE or OMC.3 Similarly, general quality-of-life benefit as assessed with Short Form-12 Physical Component Summary (SF-12 PCS)7 was similar for ST and SE when compared with OMC.3 Long-term results, however, showed similar and sustained benefits for both ST and SE over OMC in treadmill walking performance, but PAQ summary score was more favorable …

Lipoprotein-associated phospholipase A2 (LpPLA2) activity was associated with higher CHD risk in a meta-analysis, which was partly dependent on circulating lipid levels. Apolipoprotein C3 loss-of-function (ApoC3 LOF) mutations were related with reduced postprandial lipemia and CHD risk. However, the association of LpPLA2 activity with ApoC3 LOF is not known.We examined the association of LpPLA2 activity and ApoC3 LOF mutations and incident cardiovascular disease (CVD) (defined as coronary heart disease [CHD] plus ischemic stroke) and all-cause mortality in the biracial longitudinal Atherosclerosis Risk In Communities (ARIC) study.The mean LpPLA2 activity was 229.3 nmol/min/mL and was higher in men and whites. LpPLA2 activity correlated positively with atherogenic dyslipidemia. ApoC3 LOF carriers had lower LpPLA2 activity levels compared to non-carriers, and there was inverse association between LpPLA2 activity and ApoC3 LOF mutations in whites. In a fully adjusted model, greater LpPLA2 activity was independently associated with incident CVD (HR 1.35, 1.09-1.68 for highest vs. lowest quintile), which was mainly explained by its association with CHD, and was also associated with all-cause mortality (HR 1.65, 1.38-1.98).Greater LpPLA2 activity was associated with increased CHD and all-cause mortality in both whites and African-Americans in the ARIC study. The inverse relation between LpPLA2 activity and ApoC3 LOF mutations suggests that delayed lipoprotein clearance may at least in part explain the observed association of LpPLA2 activity with increased CVD risk.

Based on observational studies, there is a linear increase in cardiovascular risk with higher systolic blood pressure (SBP), yet clinical trials have not shown benefit across all SBP categories. We assessed whether troponin T measured using high-sensitivity assay was associated with cardiovascular disease within SBP categories in 11 191 Atherosclerosis Risk in Communities study participants. Rested sitting SBP by 10-mm Hg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease, and stroke were ascertained for a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with SBP

While there is increasing emphasis on incorporating patient-reported outcome measures in routine care for patients with heart failure (HF), how best to interpret longitudinally collected patient-reported outcome measures is unknown.To examine the strength of association between prior, current, or a change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores with death and hospitalization in patients with HF with preserved (HFpEF) and reduced (HFrEF) ejection fractions.Secondary analyses of the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial of 1372 patients with HFpEF, conducted between August 2006 and January 2012, and the HF-ACTION trial that included 1669 patients with HFrEF, conducted between April 2003 and February 2007.Prior, current, and change in KCCQ Overall Summary scores (KCCQ-os) in 5-point increments (higher scores indicate better health status).Time to cardiovascular death/first HF hospitalization (primary outcome) and all-cause death (secondary outcome).Of 1767 eligible TOPCAT participants, 882 were women (49.9%), and the mean (SD) age was 71.5 (9.7) years. Of 2130 eligible HF-ACTION participants, 599 were women (28.1%), and the mean age was 58.6 (12.7) years. Each 5-point difference in prior or current KCCQ-os scores was associated with a 6% (95% CI, 4%-8%; P .001) to 9% (95% CI, 7%-11%; P .001) lower risk for subsequent cardiovascular death/first HF hospitalization in patients with HFpEF and 6% (95% CI, 4%-9%; P .001) to 8% (95% CI, 5%-10%; P .001) lower risk for subsequent cardiovascular death/first HF hospitalization in patients with HRpEF and HFrEF in unadjusted analyses. Results were similar for change in KCCQ-os. In models with the prior and current KCCQ-os, only the current KCCQ-os was significantly associated with 10% (95% CI, 7%-12%; P.001) and 7% (95% CI, 3%-11%; P.001) lower risk for subsequent cardiovascular death/first HF hospitalization in patients with HFpEF and HFrEF, respectively. Similar results were observed when the current and Δ KCCQ-os were considered together, when adjusted for important patient and treatment characteristics, when including 3 sequential KCCQ-os scores, and when examining all-cause death as the outcome.In serial health status evaluations of patients with HF, the most recent KCCQ score was most strongly associated with subsequent death and cardiovascular hospitalization in HFpEF and HFrEF. Measuring serial patient-reported outcome measures in the clinical care of patients with HF can provide an updated assessment of prognosis.clinicaltrials.gov Identifier: NCT00094302 (TOPCAT) and NCT00047437 (HF-ACTION).

Background— Ezetimibe, when added to simvastatin therapy, reduces cardiovascular events after recent acute coronary syndrome. However, the impact of ezetimibe on cardiovascular-related hospitalizations and associated costs is unknown. Methods and Results— We used patient-level data from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to examine the impact of simvastatin–ezetimibe versus simvastatin–placebo on cardiovascular-related hospitalizations and related costs (excluding drug costs) over 7 years follow-up. Medicare Severity–Diagnosis Related Groups were assigned to all cardiovascular hospitalizations. Hospital costs were estimated using Medicare reimbursement rates for 2013. Associated physician costs were estimated as a percentage of hospital costs. The impact of treatment assignment on hospitalization rates and costs was estimated using Poisson and linear regression, respectively. There was a significantly lower cardiovascular hospitalization rate with ezetimibe compared with placebo (risk ratio, 0.95; 95% confidence interval, 0.90–0.99; P =0.031), mainly attributable to fewer hospitalizations for percutaneous coronary intervention, angina, and stroke. Consequently, cardiovascular-related hospitalization costs over 7 years were $453 per patient lower with ezetimibe (95% confidence interval, −$38 to −$869; P =0.030). Although all prespecified subgroups had lower cost with ezetimibe therapy, patients with diabetes mellitus, patients aged ≥75 years, and patients at higher predicted risk for recurrent ischemic events had even greater cost offsets. Conclusions— Addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome leads to reductions in cardiovascular-related hospitalizations and associated costs, with the greatest cost offsets in high-risk patients. These cost reductions may completely offset the cost of the drug once ezetimibe becomes generic, and may lead to cost savings from the perspective of the healthcare system, if treatment with ezetimibe is targeted to high-risk patients. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique Identifier: NCT00202878

Background— In SPRINT (Systolic Blood Pressure Intervention Trial), patients with hypertension and high cardiovascular risk treated with intensive blood pressure (BP) control ( Methods and Results— Using patient-level data from 9361 randomized patients in SPRINT, we developed models to predict risk for MACE or death and treatment-related SAE to allow for individualized BP treatment goals based on each patient’s projected risk and benefit of intensive versus standard BP control. Models were internally validated using bootstrap resampling and externally validated on 4741 patients from the ACCORD-BP (The Action to Control Cardiovascular Risk in Diabetes blood pressure) trial. Among 9361 SPRINT patients, 755 patients (8.1%) had a MACE or death event and 338 patients (3.6%) had a treatment-related SAE during a median follow-up of 3.3 years. The MACE/death and the SAE model had C statistics of 0.72 and 0.70, respectively, in the derivation cohort and 0.69 and 0.65 in ACCORD. The MACE/death model had 10 variables including treatment interactions with age, baseline systolic BP, and diastolic BP, and the SAE model had 8 variables including treatment interaction with number of BP medications. Intensive BP treatment was associated with a mean 2.2±2.6% lower risk of MACE/death compared with standard treatment (range, 20.7% lower risk to 19.6% greater risk among individual patients) and a mean 2.2±1.2% higher risk for SAEs (range, 0.5%–15.8% more harm in individual patients). Conclusions— To translate the findings from SPRINT to clinical practice, we developed prediction models to tailor the intensity of BP control based on the projected risk and benefit for each unique patient. This approach should be prospectively tested to better engage patients in shared medical decision making and to improve outcomes. Clinical Trial Registration— URL: https://clinicaltrials.gov . Unique identifier: NCT01206062.

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline recommends moderate-intensity to high-intensity statin therapy in eligible patients.To examine adoption of the 2013 ACC/AHA guideline in US cardiology practices.Among 161 cardiology practices, trends in the use of moderate-intensity to high-intensity statin and nonstatin lipid-lowering therapy (LLT) were analyzed before (September 1, 2012, to November 1, 2013) and after (February 1, 2014, to April 1, 2015) publication of the 2013 ACC/AHA guideline among 4 mutually exclusive risk groups within the ACC Practice Innovation and Clinical Excellence Registry. Interrupted time series analysis was used to evaluate for differences in trend in use of moderate-intensity to high-intensity statin and nonstatin LLT use in hierarchical logistic regression models. Participants were a population-based sample of 1 105 356 preguideline patients (2 431 192 patient encounters) and 1 116 472 postguideline patients (2 377 219 patient encounters). Approximately 97% of patients had atherosclerotic cardiovascular disease (ASCVD).Moderate-intensity to high-intensity statin and nonstatin LLT use before and after publication of the 2013 ACC/AHA guideline.Time trend in the use of moderate-intensity to high-intensity statin and nonstatin LLT.In the study cohort, the mean (SD) age was 69.6 (12.1) years among 1 105 356 patients (40.2% female) before publication of the guideline and 70.0 (11.9) years among 1 116 472 patients (39.8% female) after publication of the guideline. Although there was a trend toward increasing use of moderate-intensity to high-intensity statins overall and in the ASCVD cohort, such a trend was already present before publication of the guideline. No significant difference in trend in the use of moderate-intensity to high-intensity statins was observed in other groups. The use of moderate-intensity to high-intensity statin therapy was 62.1% (before publication of the guideline) and 66.6% (after publication of the guideline) in the overall cohort, 62.7% (before publication) and 67.0% (after publication) in the ASCVD cohort, 50.6% (before publication) and 52.3% (after publication) in the cohort with elevated low-density lipoprotein cholesterol levels (ie, ≥190 mg/dL), 52.4% (before publication) and 55.2% (after publication) in the diabetes cohort, and 41.9% (before publication) and 46.9% (after publication) in the remaining group with 10-year ASCVD risk of 7.5% or higher. In hierarchical logistic regression models, there was a significant increase in the use of moderate-intensity to high-intensity statins in the overall cohort (4.8%) and in the ASCVD cohort (4.3%) (P .01 for slope for both). There was no significant change for other risk cohorts. Nonstatin LLT use remained unchanged in the preguideline and postguideline periods in the hierarchical logistic regression models for all of the risk groups.Adoption of the 2013 ACC/AHA Cholesterol Management Guideline in cardiology practices was modest. Timely interventions are needed to improve guideline-concordant practice to reduce the burden of ASCVD.