Persistence of significant secondary mitral regurgitation post-cardiac resynchronization therapy and survival: a systematic review and meta-analysis : Mitral regurgitation and mortality post-CRT.

Cardiac resynchronization therapy (CRT) significantly reduces secondary mitral regurgitation (MR) in patients with severe left ventricular systolic dysfunction. However, uncertainty remains as to whether improvement in secondary MR correlates with improvement with mortality seen in CRT. We conducted a meta-analysis to determine the association of persistent unimproved significant secondary MR (defined as moderate or moderate-to-severe or severe MR) compared to improved MR (no MR or mild MR) post-CRT with all-cause mortality, cardiovascular mortality, and heart failure hospitalization. A systematic search of PubMed, EMBASE, and Cochrane Library databases till July 31, 2022 identified studies reporting clinical outcomes by post-CRT secondary MR status. In 12 prospective studies of 4954 patients (weighted mean age 66.8 years, men 77.8%), the median duration of follow-up post-CRT at which patients were re-evaluated for significant secondary MR was 6 months and showed significant relative risk reduction of 30% compared to pre-CRT. The median duration of follow-up post-CRT for ascertainment of main clinical outcomes was 38 months. The random effects pooled hazard ratio (95% confidence interval) of all-cause mortality in patients with unimproved secondary MR compared to improved secondary MR was 2.00 (1.57-2.55); p < 0.001). There was insufficient data to evaluate secondary outcomes in a meta-analysis, but limited data that examined the relationship showed significant association of unimproved secondary MR with increased cardiovascular mortality and heart failure hospitalization. The findings of this meta-analysis suggest that lack of improvement in secondary MR post-CRT is associated with significantly elevated risk of all-cause mortality and possibly cardiovascular mortality and heart failure hospitalization. Future studies may investigate approaches to address persistent secondary MR post-CRT to help improved outcome in this population.

Evolution and prognosis of tricuspid and mitral regurgitation following cardiac implantable electronic devices: a systematic review and meta-analysis.

AIMS: Significant changes in tricuspid regurgitation (TR) and mitral regurgitation (MR) post-cardiac implantable electronic devices (CIEDs) are increasingly recognized. However, uncertainty remains as to whether the risk of CIED-associated TR and MR differs with right ventricular pacing (RVP) via CIED with trans-tricuspid RV leads, compared with cardiac resynchronization therapy (CRT), conduction system pacing (CSP), and leadless pacing (LP). The study aims to synthesize extant data on risk and prognosis of significant post-CIED TR and MR across pacing strategies. METHODS AND RESULTS: We searched PubMed, EMBASE, and Cochrane Library databases published until 31 October 2023. Significant post-CIED TR and MR were defined as ≥ moderate. Fifty-seven TR studies (n = 13 723 patients) and 90 MR studies (n = 14 387 patients) were included. For all CIED, the risk of post-CIED TR increased [pooled odds ratio (OR) = 2.46 and 95% CI = 1.88-3.22], while the risk of post-CIED MR reduced (OR = 0.74, 95% CI = 0.58-0.94) after 12 and 6 months of median follow-up, respectively. Right ventricular pacing via CIED with trans-tricuspid RV leads was associated with increased risk of post-CIED TR (OR = 4.54, 95% CI = 3.14-6.57) and post-CIED MR (OR = 2.24, 95% CI = 1.18-4.26). Binarily, CSP did not alter TR risk (OR = 0.37, 95% CI = 0.13-1.02), but significantly reduced MR (OR = 0.15, 95% CI = 0.03-0.62). Cardiac resynchronization therapy did not significantly change TR risk (OR = 1.09, 95% CI = 0.55-2.17), but significantly reduced MR with prevalence pre-CRT of 43%, decreasing post-CRT to 22% (OR = 0.49, 95% CI = 0.40-0.61). There was no significant association of LP with post-CIED TR (OR = 1.15, 95% CI = 0.83-1.59) or MR (OR = 1.31, 95% CI = 0.72-2.39). Cardiac implantable electronic device-associated TR was independently predictive of all-cause mortality [pooled hazard ratio (HR) = 1.64, 95% CI = 1.40-1.90] after median of 53 months. Mitral regurgitation persisting post-CRT independently predicted all-cause mortality (HR = 2.00, 95% CI = 1.57-2.55) after 38 months. CONCLUSION: Our findings suggest that, when possible, adoption of pacing strategies that avoid isolated trans-tricuspid RV leads may be beneficial in preventing incident or deteriorating atrioventricular valvular regurgitation and might reduce mortality.

Variation in statin prescription among veterans with HIV and known atherosclerotic cardiovascular disease.

BACKGROUND: People with HIV have increased atherosclerotic cardiovascular disease (ASCVD) risk, worse outcomes following incident ASCVD, and experience gaps in cardiovascular care, highlighting the need to improve delivery of preventive therapies in this population. OBJECTIVE: Assess patient-level correlates and inter-facility variations in statin prescription among Veterans with HIV and known ASCVD. METHODS: We studied Veterans with HIV and existing ASCVD, ie, coronary artery disease (CAD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD), who received care across 130 VA medical centers for the years 2018-2019. We assessed correlates of statin prescription using two-level hierarchical multivariable logistic regression. Median odds ratios (MORs) were used to quantify inter-facility variation in statin prescription. RESULTS: Nine thousand six hundred eight Veterans with HIV and known ASCVD (mean age 64.3 ± 8.9 years, 97% male, 48% Black) were included. Only 68% of the participants were prescribed any-statin. Substantially higher statin prescription was observed for those with diabetes (adjusted odds ratio [OR] = 2.3, 95% confidence interval [CI], 2.0-2.6), history of coronary revascularization (OR = 4.0, CI, 3.2-5.0), and receiving antiretroviral therapy (OR = 3.0, CI, 2.7-3.4). Blacks (OR = 0.7, CI, 0.6-0.9), those with non-coronary ASCVD, ie, ICVD and/or PAD only, (OR 0.53, 95% CI: 0.48-0.57), and those with history of illicit substance use (OR=0.7, CI, 0.6-0.9) were less likely to be prescribed statins. There was significant variation in statin prescription across VA facilities (10th, 90th centile: 55%, 78%), with an estimated 20% higher likelihood of difference in statin prescription practice for two clinically similar individuals treated at two comparable facilities (adjusted MOR = 1.21, CI, 1.18-1.24), and a greater variation observed for Blacks or those with non-coronary ASCVD or history of illicit drug use. CONCLUSION: In an analysis of large-scale VA data, we found suboptimal statin prescription and significant interfacility variation in statin prescription among Veterans with HIV and known ASCVD, particularly among Blacks and those with a history of non-coronary ASCVD.

Variability of adiposity indices and incident heart failure among adults with type 2 diabetes.

BACKGROUND: It remains unclear how the variability of adiposity indices relates to incident HF. This study evaluated the associations of the variability in several adiposity indices with incident heart failure (HF) in individuals with type 2 diabetes (T2DM). METHODS: We included 4073 participants from the Look AHEAD (Action for Health in Diabetes) study. We assessed variability of body mass index (BMI), waist circumference (WC), and body weight across four annual visits using three variability metrics, the variability independent of the mean (VIM), coefficient of variation (CV), and intraindividual standard deviation (SD). Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for incident HF. RESULTS: Over a median of 6.7 years, 120 participants developed incident HF. After adjusting for relevant confounders including baseline adiposity levels, the aHR for the highest (Q4) versus lowest quartile (Q1) of VIM of BMI was 3.61 (95% CI 1.91-6.80). The corresponding aHRs for CV and SD of BMI were 2.48 (95% CI 1.36-4.53) and 2.88 (1.52-5.46), respectively. Regarding WC variability, the equivalent aHRs were 1.90 (95% CI 1.11-3.26), 1.79 (95% CI 1.07-3.01), and 1.73 (1.01-2.95) for Q4 versus Q1 of VIM, CV and SD of WC, respectively. CONCLUSIONS: In a large sample of adults with T2DM, a greater variability of adiposity indices was associated with higher risks of incident HF, independently of traditional risk factors and baseline adiposity levels. Registration-URL: https://clinicaltrials.gov/ct2/show/NCT00000620 .

New Antipsychotic Prescribing Continued into Skilled Nursing Facilities Following a Heart Failure Hospitalization: a Retrospective Cohort Study.

BACKGROUND: Multimorbidity and polypharmacy are common among individuals hospitalized for heart failure (HF). Initiating high-risk medications such as antipsychotics may increase the risk of poor clinical outcomes, especially if these medications are continued unnecessarily into skilled nursing facilities (SNFs) after hospital discharge. OBJECTIVE: Examine how often older adults hospitalized with HF were initiated on antipsychotics and characteristics associated with antipsychotic continuation into SNFs after hospital discharge. DESIGN: Retrospective cohort. PARTICIPANTS: Veterans without prior outpatient antipsychotic use, who were hospitalized with HF between October 1, 2010, and September 30, 2015, and were subsequently discharged to a SNF. MAIN MEASURES: Demographics, clinical conditions, prior healthcare utilization, and antipsychotic use data were ascertained from Veterans Administration records, Minimum Data Set assessments, and Medicare claims. The outcome of interest was continuation of antipsychotics into SNFs after hospital discharge. KEY RESULTS: Among 18,008 Veterans, antipsychotics were newly prescribed for 1931 (10.7%) Veterans during the index hospitalization. Among new antipsychotic users, 415 (21.5%) continued antipsychotics in skilled nursing facilities after discharge. Dementia (adjusted OR (aOR) 1.48, 95% CI 1.11-1.98), psychosis (aOR 1.62, 95% CI 1.11-2.38), proportion of inpatient days with antipsychotic use (aOR 1.08, 95% CI 1.07-1.09, per 10% increase), inpatient use of only typical (aOR 0.47, 95% CI 0.30-0.72) or parenteral antipsychotics (aOR 0.39, 95% CI 0.20-0.78), and the day of hospital admission that antipsychotics were started (day 0-4 aOR 0.36, 95% CI 0.23-0.56; day 5-7 aOR 0.54, 95% CI 0.35-0.84 (reference: day > 7 of hospital admission)) were significant predictors of continuing antipsychotics into SNFs after hospital discharge. CONCLUSIONS: Antipsychotics are initiated fairly often during HF admissions and are commonly continued into SNFs after discharge. Hospital providers should review antipsychotic indications and doses throughout admission and communicate a clear plan to SNFs if antipsychotics are continued after discharge.

Risk of ventricular arrhythmia in cardiac resynchronization therapy responders and super-responders: a systematic review and meta-analysis.

AIMS: Response to cardiac resynchronization therapy (CRT) is associated with improved survival, and reduction in heart failure hospitalization, and ventricular arrhythmia (VA) risk. However, the impact of CRT super-response [CRT-SR, increase in left ventricular ejection fraction (LVEF) to ≥ 50%] on VA remains unclear. METHODS AND RESULTS: We undertook a meta-analysis aimed at determining the impact of CRT response and CRT-SR on risk of VA and all-cause mortality. Systematic search of PubMed, EMBASE, and Cochrane databases, identifying all relevant English articles published until 31 December 2019. A total of 34 studies (7605 patients for VA and 5874 patients for all-cause mortality) were retained for the meta-analysis. The pooled cumulative incidence of appropriate implantable cardioverter-defibrillator therapy for VA was significantly lower at 13.0% (4.5% per annum) in CRT-responders, vs. 29.0% (annualized rate of 10.0%) in CRT non-responders, relative risk (RR) 0.47 [95% confidence interval (CI) 0.39-0.56, P < 0.0001]; all-cause mortality 3.5% vs. 9.1% per annum, RR of 0.38 (95% CI 0.30-0.49, P < 0.0001). The pooled incidence of VA was significantly lower in CRT-SR compared with CRT non-super-responders (non-responders + responders) at 0.9% vs. 3.8% per annum, respectively, RR 0.22 (95% CI 0.12-0.40, P < 0.0001); as well as all-cause mortality at 2.0% vs. 4.3%, respectively, RR 0.47 (95% CI 0.33-0.66, P < 0.0001). CONCLUSIONS: Cardiac resynchronization therapy super-responders have low absolute risk of VA and all-cause mortality. However, there remains a non-trivial residual absolute risk of these adverse outcomes in CRT responders. These findings suggest that among CRT responders, there may be a continued clinical benefit of defibrillators.

Association between cumulative social risk, particulate matter environmental pollutant exposure, and cardiovascular disease risk.

BACKGROUND: Long-term exposure to pollution has been shown to increase risk of cardiovascular disease (CVD) and mortality, and may contribute to the increased risk of CVD among individuals with higher social risk. METHODS: Data from the community-based Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were used to quantify Cumulative Social Risk (CSR) by assigning a score of 1 for the presence of each of 4 social risk factors: racial minority, single living, low income, and low educational status. 1-year average air pollution exposure to PM2.5 was estimated using land-use regression models. Associations with clinical outcomes were assessed using Cox models, adjusting for traditional CVD risk factors. The primary clinical outcome was combined all-cause mortality and nonfatal CVD events. RESULTS: Data were available on 1933 participants (mean age 59 years, 66% female, 44% Black). In a median follow up time of 8.3 years, 137 primary clinical outcome events occurred. PM2.5 exposure increased with higher CSR score. PM2.5 was independently associated with clinical outcome (adjusted hazard ratio [HR]: 1.19 [95% CI: 1.00, 1.41]). Participants with ≥2 CSR factors had an adjusted HR of 2.34 (1.48-3.68) compared to those with CSR = 0. The association was attenuated after accounting for PM2.5 (HR: 2.16; [1.34, 3.49]). Mediation analyses indicate that PM2.5 explained 13% of the risk of clinical outcome in individuals with CSR score ≥ 2. CONCLUSION: In a community-based cohort study, we found that the association of increasing CSR with higher CVD and mortality risks is partially accounted for by exposure to PM2.5 environmental pollutants.

The role of coronary artery calcification testing in incident coronary artery disease risk prediction in type 1 diabetes.

AIMS/HYPOTHESIS: We sought to assess the role of coronary artery calcification (CAC) and its progression in predicting incident coronary artery disease (CAD) in individuals with type 1 diabetes using data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. METHODS: The present study examined 292 participants who had at least one CAC measure and were free from CAD at baseline; 181 (62%) had repeat CAC assessments 4-8 years later and did not develop CAD between the two CAC measures. The HRs of incident CAD events were estimated using Cox models in categorised or in appropriately transformed CAC scores. C statistics and net reclassification improvement (NRI) were used to assess the added predictive value of CAC for incident CAD. RESULTS: At baseline, the mean age of participants was 39.4 years and the mean diabetes duration was 29.5 years. There were 76 participants who experienced a first incident CAD event over an average follow-up of 10.7 years. At baseline, compared with those without CAC (Agatston score = 0), the adjusted HR (95% CI) in groups of 1-99, 100-399 and ≥400 was 3.1 (1.6, 6.1), 4.4 (2.0, 9.5) and 4.8 (1.9, 12.0), respectively. CAC density was inversely associated with incident CAD in those with CAC volume ≥100 (HR 0.3 [95% CI 0.1, 0.9]) after adjusting for volume score. Among participants with repeated CAC measures, annual CAC progression was positively associated with incident CAD after controlling for baseline CAC. The HR (95% CI) for above vs below the median annual CAC volume progression was 3.2 (1.2, 8.5). When compared with a model that only included established risk factors, the addition of CAC improved the predictive ability for incident CAD events in the whole group. CONCLUSIONS/INTERPRETATION: CAC is strongly associated with incident CAD events in individuals with type 1 diabetes; its inclusion in CAD risk models may lead to improvement in prediction over established risk factors.

Particulate Matter Air Pollution and Racial Differences in Cardiovascular Disease Risk.

OBJECTIVE: We aimed to assess racial differences in air pollution exposures to ambient fine particulate matter (particles with median aerodynamic diameter <2.5 µm [PM2.5]) and black carbon (BC) and their association with cardiovascular disease (CVD) risk factors, arterial endothelial function, incident CVD events, and all-cause mortality. APPROACH AND RESULTS: Data from the HeartSCORE study (Heart Strategies Concentrating on Risk Evaluation) were used to estimate 1-year average air pollution exposure to PM2.5 and BC using land use regression models. Correlates of PM2.5 and BC were assessed using linear regression models. Associations with clinical outcomes were determined using Cox proportional hazards models, adjusting for traditional CVD risk factors. Data were available on 1717 participants (66% women; 45% blacks; 59±8 years). Blacks had significantly higher exposure to PM2.5 (mean 16.1±0.75 versus 15.7±0.73µg/m3; P=0.001) and BC (1.19±0.11 versus 1.16±0.13abs; P=0.001) compared with whites. Exposure to PM2.5, but not BC, was independently associated with higher blood glucose and worse arterial endothelial function. PM2.5 was associated with a higher risk of incident CVD events and all-cause mortality combined for median follow-up of 8.3 years. Blacks had 1.45 (95% CI, 1.00-2.09) higher risk of combined CVD events and all-cause mortality than whites in models adjusted for relevant covariates. This association was modestly attenuated with adjustment for PM2.5. CONCLUSIONS: PM2.5 exposure was associated with elevated blood glucose, worse endothelial function, and incident CVD events and all-cause mortality. Blacks had a higher rate of incident CVD events and all-cause mortality than whites that was only partly explained by higher exposure to PM2.5.

Association of obstructive sleep apnea with microvascular endothelial dysfunction and subclinical coronary artery disease in a community-based population.

Studies have reported an association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD) morbidity and mortality. Proposed mechanisms include endothelial dysfunction and atherosclerosis. We aimed to investigate the associations of OSA with endothelial dysfunction and subclinical atherosclerotic coronary artery disease (CAD), and assess the impact of race on these associations. We used data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, a community-based prospective cohort with approximately equal representation of black and white participants. OSA severity was measured in 765 individuals using the apnea-hypopnea index (AHI). Endothelial dysfunction was measured using the Endo-PAT device, expressed as Framingham reactive hyperemia index (F_RHI). Coronary artery calcium (CAC), a marker of subclinical CAD, was quantified by electron beam computed tomography. There were 498 (65%) female participants, 282 (37%) black individuals, and 204 (26%) participants with moderate/severe OSA (AHI ≥15). In univariate models, moderate/severe OSA was associated with lower F_RHI and higher CAC, as well as several traditional CVD risk factors including older age, male sex, hypertension, diabetes, higher body mass index, and lower high-density lipoprotein cholesterol levels. In a multivariable model, individuals with moderate/severe OSA had 10% lower F_RHI and 35% higher CAC, which did not reach statistical significance ( p=0.08 for both comparisons). There was no significant interaction of race on the association of OSA with F_RHI or CAC ( p-value >0.1 for all comparisons). In a community-based cohort comprised of black and white participants, moderate/severe OSA was modestly associated with endothelial dysfunction and subclinical atherosclerotic CAD. These associations did not vary by race.

Association of cumulative social risk with mortality and adverse cardiovascular disease outcomes.

BACKGROUND: Quantifying the cumulative effect of social risk factors on cardiovascular disease (CVD) risk can help to better understand the sources of disparities in health outcomes. METHOD AND RESULTS: Data from the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study were used to create an index of cumulative social risk (CSR) and quantify its association with incident CVD and all-cause mortality. CSR was defined by assigning a score of 1 for the presence of each of 4 social factors: i) racial minority status (Black race), ii) single living status, iii) low income, and iv) low educational level. Hazard ratios (HRs) were computed using Cox-regression models, adjusted for CVD risk factors. Over a median follow-up period of 8.3 years, 127 incident events were observed. The incidence of the primary outcome for subgroups of participants with 0, 1, and ≥2 CSR scores was 5.31 (95% CI, 3.40-7.22), 10.32 (7.16-13.49) and 17.80 (12.94-22.67) per 1000 person-years, respectively. Individuals with CSR score of 1 had an adjusted HR of 1.85 (1.15-2.97) for incident primary outcomes, compared to those with score of 0. The corresponding HR for individuals with CSR score of 2 or more was 2.58 (1.60-4.17). CONCLUSION: An accumulation of social risk factors independently increased the likelihood of CVD events and deaths in a cohort of White and Black individuals.

Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESES: Current evidence indicates that statins increase the risk of incident diabetes; however, the relationship between statins and glycaemic control in people with established diabetes has not been well characterised. To address this question, we conducted a meta-analysis of randomised controlled trials (RCTs) of statins in patients with diabetes for whom there was available data on glycaemic control. METHODS: We identified studies published between January 1970 and November 2013 by searching electronic databases and reference lists. We included RCTs in which the intervention group received statins and the control group received placebo or standard treatment, with >200 participants enrolled, with the intervention lasting >12 weeks and with pre- and post-intervention HbA1c reported. We combined study-specific estimates using random-effects model meta-analysis. RESULTS: In a pooled analysis of nine trials involving 9,696 participants (4,980 statin, 4,716 control) and an average follow-up of 3.6 years, the mean HbA1c of participants randomised to statins was higher than those randomised to the control group: mean difference (95% CI) was 0.12% (0.04, 0.20) or 1.3 mmol/mol (0.4, 2.2); p = 0.003. There was moderate heterogeneity across the studies (I (2) = 54%, p = 0.014) not explained by available study-level characteristics. This review was limited by the small number of studies, available data on only three statins and sparse reporting on changes in use of glucose-lowering medications. CONCLUSIONS/INTERPRETATION: Statin treatment is associated with a modest increase in HbA1c in patients with diabetes.

Risk of death and readmission among individuals with heart failure and HIV: A systematic review and meta-analysis.

The association between human immunodeficiency virus (HIV) status and readmissions and death outcomes in patients with established heart failure (HF) remains unclear. We conducted a systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science up to March 1st, 2023, for cohort studies of adult patients (≥18 years) diagnosed with HF and recorded HIV status at baseline. Our analysis included 7 studies with 10,328 HF patients living with HIV and 48,757 HF patients without HIV. Compared to HF patients without HIV, those with HIV had a higher risk of all-cause deaths (HR: 1.20, 95% CI: 1.15-1.25). HIV infection was also associated with increased risks of HF-associated readmission (HR: 1.34, 95% CI: 1.03-1.75) and all-cause readmission (HR: 1.27, 95% CI: 1.10-1.46). Our study highlights the independent association between HIV and poor HF outcomes, emphasizing the need for improved management in individuals living with HIV.

Clinical Outcomes After Acute Coronary Syndromes or Revascularization Among People Living With HIV: A Systematic Review and Meta-Analysis.

Importance: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately. Objective: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group. Data Sources: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023. Study Selection: Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event. Data Extraction and Synthesis: Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis. Main Outcome and Measures: The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure. Results: A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and ß-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62). Conclusions and Relevance: These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Therapy for hepatitis C virus infection increases survival of patients with pretreatment anemia.

BACKGROUND & AIMS: Individuals with chronic hepatitis C virus (HCV) infection and pretreatment anemia are less likely to begin and complete a full course of treatment for HCV. However, among those who are treated for HCV infection, the effect of treatment on mortality is not clear. METHODS: We performed a retrospective analysis of 200,139 HCV-infected veterans using data from the Electronically Retrieved Cohort of Hepatitis C-Infected veterans (2001-2008). The effects of treatment and treatment duration on survival were compared based on data from 1820 treated and 27,690 untreated anemic HCV-infected veterans. The association between HCV treatment and mortality was estimated using the Cox proportional hazard models, with adjustments for potential confounders. The main outcome was all-cause mortality. RESULTS: In multivariable analysis, pretreatment anemia was associated significantly with African American race (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.95-2.11), chronic kidney disease (OR, 3.36; 95% CI, 3.23-3.51), and decompensated liver disease (OR, 3.69; 95% CI, 3.53-3.86). All-cause mortality for treated, anemic, HCV-infected veterans was lower (54.2 per 1000 person-years; 95% CI, 49.2-59.7 per 1000 person years) than for untreated, anemic HCV-infected veterans (146.8 per 1000 person-years; 95% CI, 144.2-149.4 per 1000 person-years). The adjusted hazard ratio for treatment of HCV in anemic veterans was 0.45 (95% CI, 0.39-0.51), which was reduced after exclusion of comorbidities (hazard ratio, 0.28; 95% CI, 0.22-0.37). CONCLUSIONS: Based on a retrospective analysis of a veterans database, HCV therapy increases survival rates of individuals with pretreatment anemia. Additional studies are needed to determine strategies to increase rates of HCV therapy for this group.

Type 1 diabetes and risk of heart failure: A systematic review and meta-analysis.

AIM: Robust data on type 1 diabetes (T1DM) and the risk of heart failure (HF) is scarce. METHODS: We searched PubMed and EMBASE for relevant studies, abstracted data on HF incidence rate and adjusted relative risk (aRR) for T1DM, type 2 diabetes (T2DM) and controls, and pooled incidence rates and aRRs for HF across studies. RESULTS: Four studies including 61,885 T1DM patients, 4,599,213 non-diabetic controls, and 248,021 T2DM patients (three studies) were included. The pooled average proportions of men were 56%, 54%, and 55%, for T1DM, T2DM, and controls, respectively. The corresponding pooled average participants' ages were 40, 65 and 57 years, respectively. Over a 1 to 12 years follow-up, 1378, 3993, 18,945 HF events occurred among individuals with T1DM, T2DM, and controls, yielding pooled HF incidence rates of 5.8 (95%CI: 4.1-7.6), 10.0 (95% CI: 6.1-13.9), 2.3 (95% CI: 1.5-3.2) per 1000 person-years, respectively. Compared to controls, T1DM patients had a 3-fold higher HF risk (aRR 3.4, 95% CI 2.71-4.26). The RR of HF was âˆ¼ 5-fold higher in women (aRR: 4.9, 95% CI: 4.1-5.9) vs. 3-fold higher in men (aRR: 3.0, 95% CI: 2.2-4.0). CONCLUSIONS: Individuals with T1DM had a substantially higher risk of HF compared to those without diabetes.

Incidence of New Dementia Diagnosis in Veterans Admitted to Nursing Homes After Heart Failure Hospitalization.

BACKGROUND: Hospitalization with heart failure (HF) may signal an increased risk of Alzheimer's disease and related dementias (ADRD). Nursing homes routinely assess cognition but the association of these results with new ADRD diagnosis in a population at high risk of ADRD is not known. OBJECTIVE: To determine the association between nursing home cognitive assessment results and new diagnosis of dementia after heart failure hospitalization. METHODS: This retrospective cohort study included Veterans hospitalized for HF and discharged to nursing homes, from 2010 to 2015, without a prior diagnosis of ADRD. We determined mild, moderate, or severe cognitive impairment using multiple items of the nursing home admission assessment. We used Cox regression to determine the association of cognitive impairment with new ADRD diagnosis during 365 days of follow-up. RESULTS: The cohort included 7,472 residents, new diagnosis of ADRD occurred in 4,182 (56%). The adjusted hazard ratio of ADRD diagnosis was 4.5 (95% CI 4.2, 4.8) for the mild impairment group, 5.4 (95% CI 4.8, 5.9) for moderate impairment, and 4.0 (95% CI 3.2, 5.0) for severe impairment compared to the cognitively intact group. CONCLUSION: New ADRD diagnoses occurred in more than half of Veterans with HF admitted to nursing homes for post-acute care.

Acute Antipsychotic Use and Presence of Dysphagia Among Older Veterans with Heart Failure.

OBJECTIVE: Examine whether new antipsychotic (AP) exposure is associated with dysphagia in hospitalized patients with heart failure (HF). DESIGN: Retrospective cohort. SETTINGS AND PARTICIPANTS: AP-naïve Veterans hospitalized with HF and subsequently discharged to a skilled nursing facility (SNF) between October 1, 2010, and November 30, 2019. METHODS: We linked Veterans Health Administration (VHA) electronic medical records with Centers for Medicare & Medicaid (CMS) Minimum Data Set (MDS) version 3.0 assessments and CMS claims. The exposure variable was administration of ≥1 dose of a typical or atypical AP during hospitalization. Our main outcome measure was dysphagia presence defined by (1) inpatient dysphagia diagnosis codes and (2) the SNF admission MDS 3.0 swallowing-related items to examine post-acute care dysphagia status. Inverse probability of treatment weighting was used for risk adjustment. RESULTS: The analytic cohort consisted of 29,591 Veterans (mean age 78.5 ± 10.0 years; female 2.9%; n = 865). Acute APs were administered to 9.9% (n = 2941). Those receiving APs had differences in prior dementia [37.1%, n = 1091, vs 22.3%, n = 5942; standardized mean difference (SMD) = 0.33] and hospital delirium diagnoses (7.7%, n = 227 vs 2.8%, n = 754; SMD = 0.22). Acute AP exposure was associated with nearly double the risk for hospital dysphagia diagnosis codes [adjusted (adj.) relative risk (RR) 1.9, 95% CI 1.8, 2.1]. At the SNF admission MDS assessment, acute AP administration during hospitalization was associated with an increased dysphagia risk (adj. RR 1.2, 95% CI 1.0, 1.5) both in the oral (adj. RR 1.7, 95% CI 1.2, 2.0) and pharyngeal phases (adj. RR 1.3, 95% CI 1.0, 1.7). CONCLUSIONS AND IMPLICATIONS: In this retrospective study, AP medication exposure was associated with increased dysphagia coding and MDS assessment. Considering other adverse effects, acute AP should be cautiously administered during hospitalization, particularly in those with dementia. Swallowing function is critical to hydration, nutrition, and medical management of HF; therefore, when acute APs are initiated, a swallow evaluation should be considered.

Performance of Cardiovascular Risk Prediction Models Among People Living With HIV: A Systematic Review and Meta-analysis.

Importance: Extant data on the performance of cardiovascular disease (CVD) risk score models in people living with HIV have not been synthesized. Objective: To synthesize available data on the performance of the various CVD risk scores in people living with HIV. Data Sources: PubMed and Embase were searched from inception through January 31, 2021. Study Selection: Selected studies (1) were chosen based on cohort design, (2) included adults with a diagnosis of HIV, (3) assessed CVD outcomes, and (4) had available data on a minimum of 1 CVD risk score. Data Extraction and Synthesis: Relevant data related to study characteristics, CVD outcome, and risk prediction models were extracted in duplicate. Measures of calibration and discrimination are presented in tables and qualitatively summarized. Additionally, where possible, estimates of discrimination and calibration measures were combined and stratified by type of risk model. Main Outcomes and Measures: Measures of calibration and discrimination. Results: Nine unique observational studies involving 75 304 people (weighted average age, 42 years; 59 490 male individuals [79%]) living with HIV were included. In the studies reporting these data, 86% were receiving antiretroviral therapy and had a weighted average CD4+ count of 449 cells/µL. Included in the study were current smokers (50%), patients with diabetes (5%), and patients with hypertension (25%). Ten risk prediction scores (6 in the general population and 4 in the HIV-specific population) were analyzed. Most risk scores had a moderate performance in discrimination (C statistic: 0.7-0.8), without a significant difference in performance between the risk scores of the general and HIV-specific populations. One of the HIV-specific risk models (Data Collection on Adverse Effects of Anti-HIV Drugs Cohort 2016) and 2 of the general population risk models (Framingham Risk Score [FRS] and Pooled Cohort Equation [PCE] 10 year) had the highest performance in discrimination. In general, models tended to underpredict CVD risk, except for FRS and PCE 10-year scores, which were better calibrated. There was substantial heterogeneity across the studies, with only a few studies contributing data for each risk score. Conclusions and Relevance: Results of this systematic review and meta-analysis suggest that general population and HIV-specific CVD risk models had comparable, moderate discrimination ability in people living with HIV, with a general tendency to underpredict risk. These results reinforce the current recommendations provided by the American College of Cardiology/American Heart Association guidelines to consider HIV as a risk-enhancing factor when estimating CVD risk.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear. OBJECTIVE: The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials. METHODS: Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic. RESULTS: In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01). CONCLUSION: PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.