Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Barriers and Facilitators to Risk Reduction of Cardiovascular Disease in Hypertensive Patients in Nigeria.

Background: In Sub-Saharan Africa (SSA), the prevalence of hypertension is increasing due to many factors like rapid population growth, globalization, stress, and urbanization. We aimed to characterize the perceptions of cardiovascular disease (CVD) risk among individuals with hypertension living in Nigeria and identify barriers and facilitators to optimal hypertension management. Methods: This cross-sectional survey study was conducted at a large teaching hospital in Lagos, Nigeria. We used a convenient sample of males and females, aged 18 or older, with a diagnosis of hypertension who presented for outpatient visits in the cardiology, nephrology, or family medicine clinics between November 1 and 30, 2020. A semiquantitative approach was utilized with a survey consisting of closed and open-ended questionnaires focused on patient knowledge, perceptions of CVD risk, and barriers and facilitators of behavioral modifications to reduce CVD risk. Results: There were 256 subjects, and 62% were female. The mean age was 58.3 years (standard deviation (SD) = 12.6). The mean duration of the hypertension diagnosis was 10.1 years. Most participants were quite knowledgeable about hypertension; however, we observed some knowledge gaps, including a belief that too much "worrying or overthinking" was a major cause of hypertension and that an absence of symptoms indicated that hypertension was under control. Barriers to hypertension management include age, discomfort or pain, and lack of time as barriers to exercise. Tasteless meals and having to cook for multiple household members were barriers to decreasing salt intake. Cost and difficulty obtaining medications were barriers to medication adherence. Primary facilitators were family support or encouragement and incorporating lifestyle modifications into daily routines. Conclusion: We identified knowledge gaps about hypertension and CVD among our study population. These gaps enable opportunities to develop targeted interventions by healthcare providers, healthcare systems, and local governments. Our findings also help in the promotion of community-based interventions that address barriers to hypertension control and promote community and family involvement in hypertension management in these settings.

Association of Dual Eligibility for Medicare and Medicaid With Heart Failure Quality and Outcomes Among Get With The Guidelines-Heart Failure Hospitals.

Importance: The Centers for Medicare & Medicaid Services uses a new peer group-based payment system to compare hospital performance as part of its Hospital Readmissions Reduction Program, which classifies hospitals into quintiles based on their share of dual-eligible beneficiaries for Medicare and Medicaid. However, little is known about the association of a hospital's share of dual-eligible beneficiaries with the quality of care and outcomes for patients with heart failure (HF). Objective: To evaluate the association between a hospital's proportion of patients with dual eligibility for Medicare and Medicaid and HF quality of care and outcomes. Design, Setting, and Participants: This retrospective cohort study evaluated 436 196 patients hospitalized for HF using the Get With The Guidelines-Heart Failure registry from January 1, 2010, to December 31, 2017. The analysis included patients 65 years or older with available data on dual-eligibility status. Hospitals were divided into quintiles based on their share of dual-eligible patients. Quality and outcomes were analyzed using unadjusted and adjusted multivariable logistic regression models. Data analysis was performed from April 1, 2020, to January 1, 2021. Main Outcomes and Measures: The primary outcome was 30-day all-cause readmission. The secondary outcomes included in-hospital mortality, 30-day HF readmissions, 30-day all-cause mortality, and HF process of care measures. Results: A total of 436 196 hospitalized HF patients 65 years or older from 535 hospital sites were identified, with 258 995 hospitalized patients (median age, 81 years; interquartile range, 74-87 years) at 455 sites meeting the study criteria and included in the primary analysis. A total of 258 995 HF hospitalizations from 455 sites were included in the primary analysis of the study. Hospitals in the highest dual-eligibility quintile (quintile 5) tended to care for patients who were younger, were more likely to be female, belonged to racial minority groups, or were located in rural areas compared with quintile 1 sites. After multivariable adjustment, hospitals with the highest quintile of dual eligibility were associated with lower rates of key process measures, including evidence-based ß-blocker prescription, measure of left ventricular function, and anticoagulation for atrial fibrillation or atrial flutter. Differences in clinical outcomes were seen with higher 30-day all-cause (adjusted odds ratio, 1.24; 95% CI, 1.14-1.35) and HF (adjusted odds ratio, 1.14; 95% CI, 1.03-1.27) readmissions in higher dual-eligible quintile 5 sites compared with quintile 1 sites. Risk-adjusted in-hospital and 30-day mortality did not significantly differ in quintile 1 vs quintile 5 hospitals. Conclusions and Relevance: In this cohort study, hospitals with a higher share of dual-eligible patients provided care with lower rates of some of the key HF quality of care process measures and with higher 30-day all-cause or HF readmissions compared with lower dual-eligibility quintile hospitals.

Mechanisms and Treatment of Dyslipidemia in Diabetes.

PURPOSE OF REVIEW: Type 2 diabetes mellitus is widespread throughout the world and is a powerful risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). This manuscript explored the mechanisms underlying dyslipidemia in type 2 diabetes as well as currently available treatment options and guideline recommendations. RECENT FINDINGS: Type 2 diabetes is associated with a characteristic pattern of dyslipidemia, often termed diabetic dyslipidemia. Patients with type 2 diabetes often present with low HDL levels, elevated levels of small dense LDL particles, and elevated triglyceride levels. LDL lowering is the cornerstone of managing diabetic dyslipidemia, and statins are the mainstay of therapy. The cholesterol absorption inhibitor ezetimibe and PCSK9 inhibitors have also been shown to lower risk in patients with diabetes. Recently, the eicosapentaenoic (EPA) only n-3 fatty acid, icosapent ethyl, has also shown benefit for cardiovascular risk reduction in patients with diabetes. To date, no agents targeting HDL increase have shown cardiovascular benefit in patients on background statin therapy. Diabetic dyslipidemia is significant cardiovascular disease risk factor, and LDL-lowering therapy with statins, PCSK9 inhibitors, and ezetimibe continues to be mainstay therapy to reduce cardiovascular risk. Future studies targeting low HDL and high triglycerides levels associated with type 2 diabetes could provide additional novel therapies to manage diabetic dyslipidemia.

Asian-Americans and Pacific Islanders in COVID-19: Emerging Disparities Amid Discrimination.

Coronavirus disease 2019 (COVID-19) is a global pandemic. In the USA, the burden of mortality and morbidity has fallen on minority populations. The understanding of the impact of this pandemic has been limited in Asian-Americans and Pacific Islanders (AAPIs), though disaggregated data suggest disproportionately high mortality rates. AAPIs are at high risk for COVID-19 transmission, in part due to their over-representation in the essential workforce, but also due to cultural factors, such as intergenerational residency, and other social determinants of health, including poverty and lack of health insurance. Some AAPI subgroups also report a high comorbidity burden, which may increase their susceptibility to more severe COVID-19 infection. Furthermore, AAPIs have encountered rising xenophobia and racism across the country, and we fear such discrimination only serves to exacerbate these rapidly emerging disparities in this community. We recommend interventions including disaggregation of mortality and morbidity data, investment in community-based healthcare, advocacy against discrimination and the use of non-inflammatory language, and a continued emphasis on underlying comorbidities, to ensure the protection of vulnerable communities and the navigation of this current crisis.

Correction: Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings.

[This corrects the article DOI: 10.5334/gh.823.].

Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings.

In this paper, we provide recommendations on the management of cardiovascular disease (CVD) among patients with confirmed or suspected coronavirus disease (COVID-19) to facilitate the decision making of healthcare professionals in low resource settings. The emergence of novel coronavirus disease, also known as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions, leading to a pandemic. There is concern that COVID-19 is cardiotropic, and it interacts with the cardiovascular system on multiple levels. Individuals with established CVD are more susceptible to severe COVID-19. Through a consensus approach involving an international group this WHF statement summarizes the links between cardiovascular disease and COVID-19 and present some practical recommendations for the management of hypertension and diabetes, acute coronary syndrome, heart failure, rheumatic heart disease, Chagas disease, and myocardial injury for patients with COVID-19 in low-resource settings. This document is not a clinical guideline and it is not intended to replace national clinical guidelines or recommendations. Given the rapidly growing burden posed by COVID-19 illness and the associated severe prognostic implication of CVD involvement, further research is required to understand the potential mechanisms linking COVID-19 and CVD, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients.

Cardiac arrhythmias in low- and middle-income countries.

Many low- and middle-income countries (LMICs) are undergoing an epidemiological transition. With an improvement in socioeconomic conditions and an aging population, cardiovascular diseases (CVDs), like cardiac arrhythmias, are expected to increase in these countries. However, there are limited studies on the epidemiology and management of cardiac arrhythmias in LMICs. This review will highlight the unique challenges and opportunities that these countries face when managing cardiac arrhythmias.

Association of Hospital Racial Composition and Payer Mix With Mortality in Acute Coronary Syndrome.

Background Patient characteristics insufficiently explain disparities in cardiovascular outcomes among hospitalized patients, suggesting a role for community or hospital-level factors. Here, we evaluate the association of hospital racial composition and payer mix with all-cause inpatient mortality for patients hospitalized with acute coronary syndrome (ACS). Methods and Results Using the National Inpatient Sample, we identified adult hospitalizations from 2014 with a primary diagnosis of ACS (n=550 005). We divided National Inpatient Sample hospitals into quartiles based on percent of minority (black, Hispanic, Asian or Pacific Islander, Native American race/ethnicity) and low-income payer (Medicaid or uninsured) discharges in 2014. We utilized logistic regression to determine whether hospital minority or low-income payer makeup associated with all-cause inpatient mortality among those admitted for ACS . In adjusted models, ACS patients admitted to hospitals with >12.4% to 25.4% (Quartile 2), >25.4% to 44.3% (Q3), and >44.3% (Q4) minority discharges experienced a 14% (OR 1.14, 95% CI 1.06-1.23), 13% (OR 1.13, 95% CI 1.04-1.23), and 15% (OR 1.15, 95% CI 1.04-1.26) increased odds of all-cause inpatient mortality compared with hospitals with ≤12.4% (Q1) minority discharges. ACS patients admitted to hospitals with >18.7% to 25.7% (Q2) and >34.0% (Q4) low-income payer discharges experienced a 9% (OR 1.09, 1.01-1.17) and 9% (OR 1.09, 1.00-1.19) increased odds of all-cause inpatient mortality when compared with hospitals with ≤18.7% (Q1) low-income payer discharges. Conclusions Hospital minority and low-income payer makeup positively associate with odds of all-cause inpatient mortality among patients admitted for acute coronary syndrome.

Hospital-Based Quality Improvement Interventions for Patients With Acute Coronary Syndrome: A Systematic Review.

BACKGROUND: Quality improvement initiatives have been developed to improve acute coronary syndrome care largely in high-income country settings. We sought to synthesize the effect size and quality of evidence from randomized controlled trials (RCTs) and nonrandomized studies for hospital-based acute coronary syndrome quality improvement interventions on clinical outcomes and process of care measures for their potential implementation in low- and middle-income country settings. METHODS AND RESULTS: We conducted a bibliometric search of databases and trial registers and a hand search in 2016 and performed an updated search in May 2018 and May 2019. We performed data extraction, risk of bias assessment, and quality of evidence assessments in duplicate. We assessed differences in outcomes by study design comparing RCTs to nonrandomized quasi-experimental studies and by country income status. A meta-analysis was not feasible due to substantial, unexplained heterogeneity among the included studies, and thus, we present a qualitative synthesis. We screened 5858 records and included 32 studies (14 RCTs [n=109 763] and 18 nonrandomized quasi-experimental studies [n=54-423]). In-hospital mortality ranged from 2.1% to 4.8% in the intervention groups versus 3.3% to 5.1% in the control groups in 5 RCTs (n=55 942). Five RCTs (n=64 313) reported 3.0% to 31.0% higher rates of reperfusion for patients with ST-segment-elevation myocardial infarction in the intervention groups. The effect sizes for in-hospital and discharge medical therapies in a majority of RCTs were 3.0% to 10.0% higher in the intervention groups. There was no significant difference in 30-day mortality evaluated by 4 RCTs (n=42 384), which reported 2.5% to 15.0% versus 5.9% to 22% 30-day mortality rates in the intervention versus control groups. In contrast, nonrandomized quasi-experimental studies reported larger effect sizes compared to RCTs. There were no significant consistent differences in outcomes between high-income and middle-income countries. Low-income countries were not represented in any of the included studies. CONCLUSIONS: Hospital-based acute coronary syndrome quality improvement interventions have a modest effect on process of care measures but not on clinical outcomes with expected differences by study design. Although quality improvement programs have an ongoing and important role for acute coronary syndrome quality of care in high-income country settings, further research will help to identify key components for contextualizing and implementing such interventions to new settings to achieve their desired effects. Systematic Review Registration: URL: https://www.crd.york.ac.uk/PROSPERO/. Unique identifier: CRD42016047604.

Hospital-based quality improvement interventions for patients with heart failure: a systematic review.

OBJECTIVE: To estimate the direction and magnitude of effect and quality of evidence for hospital-based heart failure (HF) quality improvement interventions on process of care measures and clinical outcomes among patients with acute HF. REVIEW METHODS: We performed a structured search to identify relevant randomised trials evaluating the effect of in-hospital quality improvement interventions for patients hospitalised with HF through February 2017. Studies were independently reviewed in duplicate for key characteristics, outcomes were summarised and a qualitative synthesis was performed due to substantial heterogeneity. RESULTS: From 3615 records, 14 randomised controlled trials were identified for inclusion with multifaceted interventions. There was a trend towards higher in-hospital use of ACE inhibitors (ACE-I; 57.9%vs40.0%) and beta-blockers (BBs; 46.7%vs10.2%) in the intervention than the comparator in one trial (n=429 participants). Five trials (n=78 727 participants) demonstrated no effect of the intervention on use of ACE-I or angiotensin receptor blocker at discharge. Three trials (n=89 660 participants) reported no effect on use of BB at discharge. Two trials (n=419 participants) demonstrated a trend towards lower hospital readmission up to 90 days after discharge. There was no consistent effect of the quality improvement intervention on 30-day all-cause mortality, hospital length of stay and patient-level health-related quality of life. CONCLUSIONS: Randomised trials of hospital-based HF quality improvement interventions do not show a consistent effect on most process of care measures and clinical outcomes. The overall quality of evidence for the prespecified primary and key secondary outcomes was very low to moderate, suggesting that future research will likely influence these estimates. TRIAL REGISTRATION NUMBER: CRD42016049545.

Presentation, management and outcomes of acute coronary syndrome: a registry study from Kenyatta National Hospital in Nairobi, Kenya.

BACKGROUND: Acute coronary syndrome (ACS) is understudied in sub-Saharan Africa despite its increasing disease burden. We sought to create an ACS registry at Kenyatta National Hospital to evaluate the presentation, management and outcomes of ACS patients. METHODS: From November 2016 to April 2017, we conducted a retrospective review of ACS cases managed at Kenyatta National Hospital between 2013 and 2016, with a primary discharge diagnosis of ACS, based on International Classification of Diseases (ICD) 10 coding (I20-I24). We compared the presentation, management and outcomes by ACS subtype using analysis of variance testing. We created multivariable logistic regression models using the Global Registry of Acute Coronary Events (GRACE) risk score to evaluate the association between clinical variables, including guideline-directed medical therapy and in-hospital outcomes. RESULTS: Among 196 ACS admissions, the majority (65%) was male, and the median age was 58 years. Most (57%) ACS admissions were for ST-segment-elevation myocardial infarction (STEMI). In-hospital dual antiplatelet (> 85%), beta-blockade (72%) and anticoagulant (72%) therapy was common. A minority (33%) of patients with STEMI was eligible for reperfusion therapy but only 5% received reperfusion. In-hospital mortality rate was 17%, and highest among individuals presenting with STEMI (21%). After multivariable adjustment, higher serum creatinine level was associated with higher odds of in-hospital death (OR = 1.84, 95% CI: 1.21 - 2.78), and STEMI and Killip class > 1 were associated with in-hospital composite of death, re-infarction, stroke, major bleeding or cardiac arrest (STEMI: OR = 8.70, 95% CI: 2.52 - 29.93; Killip > 1: OR = 10.7, 95% CI: 3.34-34.6). CONCLUSIONS: We describe the largest ACS registry at Kenyatta National Hospital to date and identify potential areas for improved ACS care related to diagnostics and management to optimise in-hospital outcomes.

Facilitators, context of and barriers to acute coronary syndrome care at Kenyatta National Hospital, Nairobi, Kenya: a qualitative analysis.

BACKGROUND: The prevalence of ischaemic heart disease and its acute manifestation, acute coronary syndrome (ACS), is growing throughout sub-Saharan Africa, including Kenya. To address this increasing problem, we sought to understand the facilitators, context of and barriers to ACS care at Kenyatta National Hospital, with the aim of improving the quality of care of ACS. METHODS: We conducted in-depth interviews with healthcare providers involved in the management of ACS patients from January to February 2017 at Kenyatta National Hospital in Nairobi, Kenya. We selected an initial sample of key participants for interviewing and used a snowballing technique to identify additional participants until we achieved saturation. After transcription of audio recordings of the interviews, two authors conducted data coding and analysis using a framework approach. RESULTS: We conducted 16 interviews with healthcare providers. Major themes included the need to improve the diagnostic and therapeutic capabilities of the hospital, including increasing the number of ECG machines and access to thrombolytics. Participants highlighted an overall wide availability of other guideline-directed medical therapies, including antiplatelets, beta-blockers, statins, anticoagulants and ACE inhibitors. All participants also stated the need for and openness to accepting future interventions for improvement of quality of care, including checklists and audits to improve ACS care at Kenyatta National Hospital. CONCLUSION: Major barriers to ACS care at Kenyatta National Hospital include inadequate diagnostic and therapeutic capabilities, lack of hospital-wide ACS guidelines, undertraining of healthcare providers and delayed presentation of patients seeking care. We also identified potential targets, including checklists and audits for future improvements in quality of care from the perspective of healthcare providers.

Lay beliefs about hypertension among HIV-infected adults in Kenya.

OBJECTIVE: Hypertension affects 23% of Kenyans and is the most prevalent modifiable risk factor for cardiovascular disease. Despite this, hypertension awareness and treatment adherence is very low. We conducted a qualitative study to explore lay beliefs about hypertension among HIV-infected adults to inform the development of culture sensitive hypertension prevention and control program. METHODS: Eight focus group discussions were held for 53 HIV-infected adults at the HIV clinic in Kenya. RESULTS: Respondents had difficulties in describing hypertension. Hypertension was considered a temporary illness that is fatal and more serious than HIV. Stress was perceived as a main cause for hypertension with a large majority claiming stress reduction as the best treatment modality. Alcohol and tobacco use were not linked to hypertension. Obesity was cited as a cause of hypertension but weight control was not considered as a treatment modality even though the majority of our participants were overweight. Most participants did not believe hypertension could be prevented. CONCLUSION: Our findings suggest a limited understanding of hypertension among people living with HIV and points to an urgent need to integrate hypertension education programmes in HIV care facilities in Kenya. To effect change, these programmes will need to tie in the culture meaning of hypertension.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD. OBJECTIVES: To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs. SEARCH METHODS: We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD. DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence. MAIN RESULTS: In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this update. Eight of the 13 trials evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from six weeks to 23 months. More recent trials were generally larger with longer follow-up and lower risk of bias. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Compared with the comparator groups (placebo, usual care, or active drug comparator), the effects of the fixed-dose combination treatment on mortality (FDC = 1.0% versus control = 1.0%, RR 1.10, 95% CI 0.64 to 1.89,  I2 = 0%, 5 studies, N = 5300) and fatal and non-fatal ASCVD events (FDC = 4.7% versus control = 3.7%, RR 1.26, 95% CI 0.95 to 1.66, I2 = 0%, 6 studies, N = 4517) were uncertain (low-quality evidence). The low event rates for these outcomes and indirectness of evidence for comparing fixed-dose combination to usual care versus individual drugs suggest that these results should be viewed with caution. Adverse events were common in both the intervention (32%) and comparator (27%) groups, with participants randomised to fixed-dose combination therapy being 16% (RR 1.16, 95% CI 1.09 to 1.25, 11 studies, 6906 participants, moderate-quality evidence) more likely to report an adverse event . The mean differences in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 trials, 7638 participants, moderate-quality evidence). The mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 trials, 6565 participants, low-quality evidence) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 trials, 7153 participants, moderate-quality evidence), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 80% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (26% to 65%) compared with usual care (4 trials, 3835 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS: The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain. A limited number of trials reported these outcomes, and the included trials were primarily designed to observe changes in ASCVD risk factor levels rather than clinical events, which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, active comparator, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing, longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes.

Patterns of Cardiovascular Mortality for HIV-Infected Adults in the United States: 1999 to 2013.

With widespread availability and the use of antiretroviral therapy, patients with human immunodeficiency virus (HIV) in the United States are living long enough to experience non-AIDS-defining illnesses. HIV is associated with an increased risk for cardiovascular disease (CVD) because of traditional CVD risk factors, residual virally mediated inflammation despite HIV treatment, and side effects of antiretroviral therapy. No United States population-wide studies have evaluated patterns of CVD mortality for HIV-infected subjects. Our central hypothesis was that the proportionate mortality from CVD (CVD mortality/total mortality) in the HIV-infected population increased from 1999 to 2013. We used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research online database of the United States public health data to assess proportionate CVD mortality from 1999 to 2013 in the HIV-infected, general, and inflammatory polyarthropathy populations; the inflammatory polyarthropathy population was included as a positive control group. Total mortality in the HIV-infected population decreased from 15,739 in 1999 to 8,660 in 2013; however, CVD mortality increased from 307 to 400 during the same period. Thus, proportionate CVD mortality for the HIV-infected population increased significantly from 1999 to 2013 (p <0.0001); this pattern was consistent across races, particularly for men. In contrast, proportionate CVD mortality decreased for the general and inflammatory polyarthropathy populations from 1999 to 2013. In conclusion, CVD has become an increasingly common cause of death in HIV-infected subjects since 1999; understanding evolving mortality risks in the HIV-infected population is essential to inform routine clinical care of HIV-infected subjects as well as CVD prevention and treatment.

Disparities in cardiovascular research output and citations from 52 African countries: a time-trend, bibliometric analysis (1999-2008).

BACKGROUND: Cardiovascular research output and citations of publications from Africa have historically been low yet may be increasing. However, data from the continent are limited. METHODS AND RESULTS: To evaluate the cardiovascular research output and citations from 52 African countries between 1999 and 2008, we created a bibliometric filter to capture cardiovascular research articles published in the Web of Knowledge based on specialist journals and title words. Two coauthors with expertise in cardiovascular medicine tested and refined this filter to achieve >90% precision and recall. We matched retrieved records with their associated citation reports and calculated the running 5-year citation count postpublication, including the year of publication. Publications from Africa were identified by author addresses. South Africa published 872 cardiovascular research papers, Egypt 393, Tunisia 264, and Nigeria 192 between 1999 and 2008. The number of publications increased over the time period for a small number of countries (range 0.1 to 4.8 more publications per year by fractional count). Most countries' citations were low (<50), but citations were greatest for South Africa (7063), Egypt (2557), Tunisia (903), and Nigeria (540). The same countries had the greatest annual increase in 5-year citation index values: 65 (95% CI: 30, 99) for South Africa, 46 (34, 58) for Egypt, 22 (15, 28) for Tunisia, and 8 (2, 14) for Nigeria. The burden of cardiovascular disease had a weak and inconsistent relationship to cardiovascular publications (r(2)=0.07, P=0.05). Greater gross domestic product was associated with more cardiovascular publications in 2008 (r(2)=0.53, P<0.0001). CONCLUSIONS: The increases in cardiovascular research outputs from Africa are concentrated in a few countries. The reasons for regional differences in research outputs require further investigation, particularly relative to competing disease burdens. Higher prioritization of cardiovascular research funding from African countries is warranted.