High Baseline Cardiovascular Risk Research Articles

BLOOD PRESSURE LOWERING TREATMENT AND BASELINE CARDIOVASCULAR RISK IN PRIMARY PREVENTION: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reduced cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk according to the SCORE-2 system. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 11/2022) for the effect of BP-lowering treatment against placebo, no treatment or less intense BP reduction on fatal or non-fatal CV outcomes. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We studied 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061. For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22-35%) in the category of very high-risk patients, and by 10% in the category of high-risk patients (p value for interaction = 0.020). Also, the relative risk reduction of the combined outcome was progressively greater the higher the baseline CV risk (p trend = 0.006). The risk reduction of CV death showed a significant trend from lower to higher baseline CV risk (p trend = 0.036). CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), and in the very high-risk group compared to the low-moderate risk group (p = 0.001). Conclusions: The greatest outcome benefit from BP lowering treatment in primary is observed in patients at higher baseline cardiovascular risk, as calculated by the SCORE-2.

PS-C08-8: OUTCOMES FROM BLOOD PRESSURE REDUCTION IN PATIENTS WITH DIFFERENT BASELINE CARDIOVASCULAR RISK: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reducing cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk that was assessed according to SCORE-2. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We included 54 studies (i.e., 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients, and this reduction was significantly greater (P = 0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). Moreover, CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), as well as in the very high-risk group compared to the low-moderate risk group (p = 0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p = 0.045). Conclusions: The greatest outcome benefit from BP lowering in primary prevention is observed in patients at higher baseline cardiovascular risk as calculated by the SCORE-2.

Effect of blood pressure reduction on cardiovascular outcomes in patients with different baseline cardiovascular risk: systematic review and meta-analysis of randomized trials

Abstract Background/Introduction Blood pressure (BP) lowering is accompanied by a reduction on cardiovascular (CV) outcomes and death in hypertensive patients. There is no data on the effect of lowering BP in patients stratified according to their baseline CV risk as indicated by SCORE 2. Purpose The aim of this meta-analysis was to demonstrate the impact of BP-lowering treatment on the occurrence of CV events in these previously reported patients. Methods A systematic review in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) was conducted to identify randomized trials that study the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, baseline cardiovascular risk was estimated using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results The analysis was composed of 54 studies, of which 12 trials included patients with low-to-moderate CV risk, (n=21,192 patients), 13 trials with high CV risk patients (n=66,886) and 29 trials with very high CV risk patients (n=79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients. This reduction was significantly greater (p=0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). CV death showed a significant reduction in the high-risk group of patients compared to the low-moderate risk group (p=0.005), as well as in the very high-risk group compared to the low-moderate risk group (p=0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p=0.045). Conclusions With the present meta-analysis, we observed that the greatest benefit from BP lowering in primary prevention in the occurrence of CV events and mortality is observed in patients at higher baseline cardiovascular risk, as calculated by the SCORE-2. Funding Acknowledgement Type of funding sources: None.

Cardiovascular Risks of Diclofenac Versus Other Older COX-2 Inhibitors (Meloxicam and Etodolac) and Newer COX-2 Inhibitors (Celecoxib and Etoricoxib): A Series of Nationwide Emulated Trials.

Diclofenac has increased cardiovascular risks, but its risk profile compared with other COX-2 inhibitors remains unknown. The aim of this study was to compare the cardiovascular risks of diclofenac versus other older and newer COX-2 inhibitors (coxibs). Using Danish nationwide health registries (1999-2020), we conducted a series of emulated trials (n=264). Eligible adults had no recent NSAID prescriptions, contraindications or conditions with low adherence. We included initiators of diclofenac (n=1,600,202), meloxicam (n=10,903), etodolac (n=238,538), celecoxib (n=77,591), and etoricoxib (n=12,122). We computed the adjusted intention-to-treat incidence rate ratio (aIRR) with 95% confidence interval (CI) of major adverse cardiovascular events (MACE) within 30 days of initiation (5562 events). MACE was 20% increased among initiators of diclofenac compared with other older COX-2 inhibitors (aIRR 1.19, 95% CI 1.10-1.28), driven by cardiac death (aIRR 1.57, 95% CI 1.21-2.03). The effect appeared strongest for women (aIRR 1.28, 95% CI 1.15-1.43), individuals with high baseline cardiovascular risk (aIRR 1.32, 95% CI 1.05-1.66), and when comparing high-dose diclofenac with low doses of the other older COX-2 inhibitors (aIRR 1.31, 95% CI 1.13-1.52). The results reflected increased rates compared with both meloxicam (aIRR 1.46, 95% CI 0.94-2.26) and etodolac (aIRR 1.18, 95% CI 1.09-1.28). Diclofenac initiators had similar increased rates of MACE compared with coxibs (aIRR 0.96, 95% CI 0.85-1.08), consistent for celecoxib (aIRR 1.02, 95% CI 0.88-1.19) and etoricoxib (aIRR 0.85, 95% CI 0.66-1.10). The increased cardiovascular risks associated with diclofenac initiation were higher than for other older COX-2 inhibitors (meloxicam/etodolac) and comparable to coxibs (celecoxib/etoricoxib).

BLOOD PRESSURE REDUCTION AND OUTCOMES IN PATIENTS WITH DIFFERENT BASELINE CARDIOVASCULAR RISK: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reducing cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk that was assessed according to SCORE-2. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We included 54 studies (i.e., 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients, and this reduction was significantly greater (P = 0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). Moreover, CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), as well as in the very high-risk group compared to the low-moderate risk group (p = 0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p = 0.045). Conclusions: The greatest outcome benefit from BP lowering in primary prevention is observed in patients at higher baseline cardiovascular risk as calculated by the SCORE-2.

MO731: Predictors of Early and 1-Year Mortality After an Acute Coronary Event in Haemodialysis Patients

Abstract BACKGROUND AND AIMS Cardiovascular disease (CVD) is the leading cause of mortality in haemodialysis (HD) patients (40%), mainly secondary to a coronary event (17%). According to the European Society of Cardiology (ESC), beta-blockers (BBs), anti-platelets, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) and statins are the cornerstones of CVD prevention. However, a great percentage of dialysis patients remain undermedicated. Our aim is to identify the predictors of mortality in HD patients after an acute myocardial infarction (AMI) during hospitalization and 1 year after the cardiac event. Methods We performed an observational retrospective study of all HD patients admitted to the coronary intensive care unit between January 2017 and December 2020 due to a myocardial infarction. Our variables of interest were collected before and after hospital discharge and 1 year after. We assessed patients’ frailty using the clinical frailty scale (CFS) and baseline cardiovascular (CV) risk using ESC’s classification; as we focused in HD patients (very-high risk of CVD), we classified CV risk regardless of the kidney disease. IBM SPSS 23.0 was used to perform statistical analysis; the confidence interval (CI) was set at 95%. RESULTS We collected 70 patients (males: n = 51, 73.2%), with a mean age of 70.9 ± 12.2 years and a median time in HD of 73.2 ± 60 months. Identifiable CV risk factors were: dyslipidaemia (98.6%), arterial hypertension (95.7%), heart failure (74.3%), diabetes (57.1%) and obesity (55.7%); mean total cholesterol and low-density lipoprotein cholesterol (LDL) levels were 151 ± 39.6 and 97.5 ± 34.1 mg/dL, respectively. As a result, 81.4% of our sample was classified as having a very high baseline CV risk. Before admission, most patients were on statin therapy (87.1%), but only 34.2% were taking the proper statin class/dosage adjusted to their CV risk. In fact, only 7.1% were previously medicated with all prognosis-modifying drugs (ACEis/ARBs, statins, anti-platelets and BBs). The mean hospitalization stay was 10.3 ± 9 days, and the early mortality rate (30 days post-admission) was 18.6%. Mortality was higher in older patients (72.5 ± 10.3 versus 69.1 ± 10.9 years; P = .3), males (21.6 versus 10.5%), with longer HD vintage (82.8 ± 46.8 versus 70.8 ± 48 months; P = 0.41) and higher CV risk (very-high CV risk, 84.6 versus 80%; P = .7); hypoalbuminemia (serum albumin < 3.0 g/dL) (OR 5.4, 95% CI 1.2–25.1; P = .028) and higher frailty score (CFS ≥ 4) (OR 6.1, 95% CI 1.2–30.0; P = .002) prompt a worse short-term prognosis. The mortality rate after 1 year was 30%, with a median time of 5.6 ± 2.4 months since the cardiac event. Mortality was also higher in older patients (71.5 ± 10 versus 69 ± 10 years; P = .34), males (31.3 versus 26.3%; P = 0.70), with longer dialysis vintage (85.2 ± 45.6 versus 67.2 ± 48; P = .14) and longer hospitalizations (12.8 ± 9.9 versus 9.3 ± 8.3; P = .12). After discharge, patients prescribed with at least three prognosis-modifying drugs had a lower 1-year mortality rate (3.2 versus 26.9%; OR 11, 95% CI 1.2–97.0; P = .003). Hypoalbuminemia (OR 9.4, 95% CI 2.3–4.3’; P = .002) and higher frailty scores (CFS ≥ 4) (OR 4.1, 95% CI 1.2–14.0; P = .025) were associated with worse outcomes. CONCLUSION We concluded that most HD patients were undermedicated prior to a coronary event given their baseline CV risk. Despite most studies in HD patients did not find a beneficial long-term effect of starting statin therapy after HD initiation, one must always individualize therapy according to the patient's CV risk. In our series, better-nourished patients with at least three prognosis-modifying drugs had a lower mortality rate, which highlights the importance of these drugs on survival together with optimal nutritional care.

Efficacy of vildagliptin on 10-year cardiovascular risk reduction in Thai patients with type 2 diabetes mellitus: A real-world observational study

Background and aimsThis study aimed to assess the effects of vildagliptin on the prevention of cardiovascular diseases in Thai patients with type 2 diabetes mellitus using the Thai Cardiovascular Risk Score. MethodsAll patients with type 2 diabetes mellitus who used vildagliptin at a secondary hospital in Thailand were screened and recruited. The relevant variables were obtained from patient medication charts at the first visit on which the patients were prescribed vildagliptin and from the 6-month, 12-month, and 18-month post-treatment visits. The Thai Cardiovascular Risk Score was calculated and monitored as a primary outcome, whereas changes in separate cardiometabolic parameters were assessed as secondary outcomes. ResultsOf the 321 patients screened, only 95 were recruited for the analysis. The average 10-year cardiovascular risks of patients increased from 19.65% at baseline to 20.74%, 20.69%, and 23.78% at 6, 12, and 18 months post treatment, respectively. However, a better trend of reduction in cardiovascular risk was observed in patients with a high baseline cardiovascular risk. The glucose-lowering effects of vildagliptin were significantly observed 12 months of treatment onwards, but non-significant changes were found in lipid and blood pressure levels as well as body mass index. ConclusionVildagliptin provided a promising glucose-lowering effect in Thai patients with type 2 diabetes mellitus. However, the mean 10-year cardiovascular risk did not significantly decrease. However, a negative correlation between cardiovascular risk reduction and baseline cardiovascular risk was observed in this study. Low sample size was a major limitation of this study.

Residual cardiovascular risk of patients with dyslipidemia receiving multifactorial cardiovascular prevention therapy

Abstract Background Few studies have reported on the incidence and risk factors of cardiovascular disease (CVD) in patients with dyslipidemia receiving multifactorial treatment. Purpose To record CVD incidence and risk factors in patients with dyslipidemia receiving multifactorial CVD prevention therapy. Methods This was a retrospective observational study including consecutive adult patients with dyslipidemia who were followed for ≥3 years at the outpatient Lipid Clinic of our University General Hospital. We recorded CVD incidence and compared it with ATTICA study, an epidemiological prospective cohort assessing the 10-year cardiovascular risk in a representative sample of the general population in Greece. Factors that were significantly associated with incident CVD were additionally identified. Results A total of 1,334 individuals were included and followed-up for 6 (4–10) years. Lipid-lowering treatment was overall prescribed to 94% of study participants, while 70% were on antihypertensive and 20% on glucose-lowering therapy. During follow-up, 95 subjects (7%) developed CVD events. Despite higher baseline cardiovascular risk, CVD incidence rate in this study was lower compared with ATTICA (10.4 vs 15.7/1,000 person-years, respectively). Diabetes (HR: 2.09, 95% CI: 1.18–3.70, p<0.001), established CVD at baseline (HR: 2.04, 95% CI: 1.21–3.43, p<0.001), smoking (HR: 1.82, 95% CI: 1.17–2.84, p<0.001) and age (HR: 1.07, 95% CI: 1.4–1.9, p<0.001) were independently associated with incident CVD. Conclusions CVD incidence rate of high-risk dyslipidemic patients receiving multifactorial treatment was lower compared with general population. Diabetes, smoking, age, and baseline CVD remain the residual CVD risk factors in dyslipidemic patients receiving prevention therapy. Funding Acknowledgement Type of funding sources: None.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Renal denervation in hypertension patients: Proceedings from an expert consensus roundtable cosponsored by SCAI and NKF.

Assessment of Cardiovascular Risk in Transgender Patients Presenting for Gender-Affirming Care

BackgroundThe transgender population is rapidly growing in the United States and abroad. Transgender men and women are marginalized as a result of their transgender status, with resultant health repercussions. This and other factors such as increased substance use, mental health disorders, violence, and chronic stress may place transgender individuals at higher risk for cardiovascular disease. Additionally, many transgender patients pursue gender-affirming hormone therapy, which has been linked to increased rates of some cardiovascular events such as metabolic syndrome, venous thromboembolism, and stroke. Despite the likelihood of elevated cardiovascular risk in this population, there is a paucity of published data about the cardiovascular risk of this population. MethodsWe present baseline cardiovascular data from a transgender population at a large tertiary care center prior to the initiation of hormone therapy. ResultsThe described transgender population had much higher rates of mental health disorders and substance use than the general population. Furthermore, there were high rates of undiagnosed and untreated comorbidities, such as hypertension and dyslipidemia, that increase risk for cardiovascular disease. Baseline risk assessment using the ASCVD (Atherosclerotic Cardiovascular Disease) and QRISK3 calculators showed higher-than-expected cardiovascular risk, particularly given the young age of our patient population. ConclusionsTransgender individuals are at high baseline cardiovascular risk. These data help fill some important knowledge gaps in this patient subgroup, and provide us with much-needed data to help guide our management and counseling of individuals seeking this type of care.

Abstract 14600: Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors

Introduction: The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients. Methods: This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis. Results: 93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none, P =0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%, P =0.04), PCI (0 vs. 0.5%, P =1), CABG (0. vs. 0.5%, P =1), stroke (0 vs. 0%), TIA (0 vs. 0.5%, P =1), DVT (5.4 vs. 2.2%, P =0.17), PE (1.1 vs. 4.8%, P =0.17), and myocarditis (2.2 vs. 1.1%, P =0.60). There was an increased rate of pneumonitis (14 vs. 4%, P <0.001) and skin toxicity (16 vs. 0%, P <0.001). Conclusions: Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.

Reduced Cardiorespiratory Fitness and Increased Cardiovascular Mortality After Prolonged Androgen Deprivation Therapy for Prostate Cancer

BackgroundProlonged androgen deprivation therapy (ADT) is favored over short-term use in patients with localized high-risk prostate cancer (PC). ObjectivesThis study sought to compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure and to explore how duration of ADT exposure influences CRF and CV mortality. MethodsRetrospective cohort study of patients referred for exercise treadmill testing (ETT) after a PC diagnosis. PC risk classification was based on Gleason score (GS): high risk if GS ≥8; intermediate risk if GS = 7; and low risk if GS <7. CRF was categorized by metabolic equivalents (METs): METs >8 defined as good CRF and METs ≤8 as reduced CRF. ADT exposure was categorized as short term (≤6 months) versus prolonged (>6 months). ResultsA total of 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0, 7.9 years) after PC diagnosis. Of those, 150 patients (24.3%) received ADT prior to the ETT; 99 with short-term and 51 with prolonged exposure. 504 patients (81.8%) had ≥2 CV risk factors. Prolonged ADT was associated with reduced CRF (odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.31 to 5.61; p = 0.007) and increased CV mortality (hazard ratio [HR]: 3.87; 95% CI: 1.16 to 12.96; p = 0.028) in adjusted analyses. Although the association between short-term ADT exposure and reduced CRF was of borderline significance (OR: 1.71; 95% CI: 1.00 to 2.94; p = 0.052), there was no association with CV mortality (HR: 1.60; 95% CI: 0.51 to 5.01; p = 0.420) in adjusted Cox regression models. ConclusionsAmong patients with PC and high baseline CV risk, prolonged ADT exposure was associated with reduced CRF and increased CV mortality.

Renal Denervation in High-Risk Patients With Hypertension

BackgroundRenal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent an attractive treatment for patients with high cardiovascular (CV) risk. It is important to determine whether baseline CV risk affects the efficacy of RDN. ObjectivesThe purpose of this study was to assess blood pressure (BP) reduction and event rates after RDN in patients with various comorbidities, testing the hypothesis that RDN is effective and durable in these high-risk populations. MethodsBP reduction and adverse events over 3 years were evaluated for several high-risk subgroups in the GSR (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry), an international registry of RDN in patients with uncontrolled hypertension (n = 2,652). Comparisons were made for patients age ≥65 years versus age <65 years, with versus without isolated systolic hypertension, with versus without atrial fibrillation, and with versus without diabetes mellitus. Baseline cardiovascular risk was estimated using the American Heart Association (AHA)/American College of Cardiology (ACC) atherosclerosis cardiovascular disease (ASCVD) risk score. ResultsReduction in 24-h systolic BP at 3 years was −8.9 ± 20.1 mm Hg for the overall cohort, and for high-risk subgroups, BP reduction was −10.4 ± 21.0 mm Hg for resistant hypertension, −8.7 ± 17.4 mm Hg in patients age ≥65 years, −10.2 ± 17.9 mm Hg in patients with diabetes, −8.6 ± 18.7 mm Hg in isolated systolic hypertension, −10.1 ± 20.3 mm Hg in chronic kidney disease, and −10.0 ± 19.1 mm Hg in atrial fibrillation (p < 0.0001 compared with baseline for all). BP reduction in patients with measurements at 6, 12, 24, and 36 months showed similar reductions in office and 24-h BP for patients with varying baseline ASCVD risk scores, which was sustained to 3 years. Adverse event rates at 3 years were higher for patients with higher baseline CV risk. ConclusionsBP reduction after RDN was similar for patients with varying high-risk comorbidities and across the range of ASCVD risk scores. The impact of baseline risk on clinical event reduction by RDN-induced BP changes could be evaluated in further studies. (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry; NCT01534299)

Cardiorespiratory fitness and cardiovascular mortality after prolonged androgen deprivation therapy for prostate cancer.

11576 Background: Androgen deprivation therapy (ADT) plays a pivotal role in management of prostate cancer (PC), with prolonged ADT favored over short-term use in the definitive treatment of high risk PC with radiation. Objectives: To compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure, and to explore how duration of ADT exposure influences CRF and CV mortality risk. Methods: This is a retrospective study of patients referred for exercise treadmill testing (ETT) after a diagnosis of PC. PC risk classification was based on Gleason score (GS) at diagnosis: high risk GS ≥ 8, intermediate risk GS= 7, and low risk GS ≤ 6. CRF was categorized according to metabolic equivalents (METs): METs ≥ 8 defined as good CRF and METs &lt; 8 as reduced CRF. ADT exposure was grouped as short-term (≤ 6 months) versus prolonged (&gt; 6 months). Results: 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0-7.9) after diagnosis of PC. 150 patients (24.3%) received ADT prior to ETT; 51 with short-term versus 99 with prolonged exposure. 524 (85.1%) patients had ≥ 2 CV risk factors, and 28 CV deaths occurred over 4.2 (interquartile range: 2.3-7.1) years following the ETT. Reduced CRF was more frequent among ADT-exposed versus ADT-naive patients (48.7 versus 32.6%, p&lt; 0.001). Prolonged ADT was associated with reduced CRF (odds ratio (OR): 2.71; 95% confidence interval (CI): 1.31-5.61; p=0.007) and increased CV mortality (hazard ratio (HR): 3.87; 95% CI: 1.16-12.96; p=0.03) in adjusted analyses. In contrast, short-term ADT exposure was not independently associated with either reduced CRF (OR 1.71; 95% CI: 1.00-2.94); p=0.05) or CV mortality (HR: 1.60; 95% CI: 0.51-5.01; p=0.42). Conclusions: Among patients with PC and high baseline CV risk, &gt; 6 months ADT exposure but not less was associated with reduced CRF and increased CV mortality. Reduced CRF may in part mediate increased CV mortality risk. Exercise interventions concurrent with prolonged ADT warrants investigation to potentially offset risk.

Cardiovascular Effects of Liraglutide.

Liraglutide is a glucagon-like 1 (GLP-1) agonist approved for treatment of type 2 diabetes and obesity. To review the cardiovascular effects of liraglutide including macrovascular and microvascular events, its use in heart failure, and its effects on heart rate and blood pressure. The impact of liraglutide on cardiovascular outcomes was examined in a large welldesigned study published in 2016, the LEADER trial. This study included 9,340 patients with advanced type 2 diabetes and high baseline cardiovascular risk. The primary outcome was the first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. After a median follow-up of 3.8 years, patients randomized to liraglutide had significant reduction in the composite primary outcome compared to patients randomized to placebo, hazard ratio (HR) 0.87; 95% CI 0.78-0.97. Death from cardiovascular causes was significantly reduced with liraglutide therapy (HR, 0.78; 95% CI 0.66-0.93), as well as death from any cause (HR, 0.85; 95% CI 0.74-0.97). In 2017, the LEADER investigators reported that nephropathy events were significantly lower after liraglutide therapy than placebo (HR 0.78; 95% CI 0.67-0.92), but there was no significant difference in retinopathy events. Meanwhile, other studies suggested that the use of liraglutide may be harmful in patients with severe heart failure, in part due to increase in heart rate. Liraglutide is a useful therapy in patients with advanced type 2 diabetes complicated by cardiovascular disease, except patients with severe heart failure. Further studies are needed to evaluate the long-term effects of liraglutide, and to see whether its beneficial effects extend to patients with type 2 diabetes and low cardiac risk.

All-cause mortality and antipsychotic use among elderly persons with high baseline cardiovascular and cerebrovascular risk: a multi-center retrospective cohort study in Italy

ABSTRACTBackground: Little is known about the comparative risk of death with atypical or conventional antipsychotics (APs) among persons with cardiovascular or cerebrovascular disease (CCD).Research design and methods: A cohort study was conducted using five Italian claims databases. New atypical AP users with CCD aged ≥65 (reference) were matched to new conventional AP users. Mortality per 100 person-years (PYs) and hazard ratios (HR), estimated using Cox models, were reported. Incidence and risk of death were estimated for persons having drug–drug interactions. Outcome occurrence was evaluated 180 days after AP initiation.Results: Overall 24,711 and 27,051 elderly new conventional and atypical AP users were identified. The mortality rate was 51.3 and 38.5 deaths per 100 PYs for conventional and atypical AP users. Mortality risk was 1.33 (95%CI: 1.27–1.39) for conventional APs. There was no increased mortality risk with single drug–drug interactions (DDIs) vs. no DDI. AP users with ≥1 DDI had a 29% higher mortality risk compared to no DDI in the first 90 days of treatment (HR: 1.29 (95% CI: 1.00–1.67)).Conclusions: Conventional APs had a higher risk of death than atypical APs among elderly persons with CCD. Having ≥1 DDI was associated with an increased risk of death.

Arterial stiffness: A helpful guide to prognosis and therapy in populations with a high baseline cardiovascular risk.

Arterial stiffness: A helpful guide to prognosis and therapy in populations with a high baseline cardiovascular risk.

Pathophysiology of ischaemic heart disease.

To summarize recent findings in the pathogenesis of ischemic heart disease (IHD) in people living with HIV (PLWH). PLWH have an elevated risk of IHD. Although incidence is declining, this condition still represents a major cause of non-AIDS-related mortality. The cause is likely multifactorial: traditional risk factors play an important role and IHD risk might be reduced with greater emphasis on primary prevention. The contribution of specific antiretroviral agents to IHD risk is changing as antiretroviral coverage increases globally and as safer agents have replaced drugs with well-described metabolic toxicities. The beneficial impact of virological suppression on antiretroviral therapy (ART) in reducing IHD is particularly evident in participants with advanced HIV infection and high baseline cardiovascular risk. The association between current abacavir use and myocardial infarction is still unexplained and indicates that mechanisms other than metabolic alterations may underlie IHD in PLWH. Consequently, the contributions of inflammation, subclinical atherosclerosis and endothelial dysfunction are receiving greater attention. Modern ART coupled with intensified efforts towards primary prevention is the cornerstone of IHD risk management in PLWH. The role of chronic inflammation and its optimal management need to be defined.

The effect of aromatase inhibitors use on endothelial function among postmenopausal women with breast cancer.

e12064 Background: Data on long-term cardiovascular effects and safety of aromatase inhibitors (AI) are limited and conflicting. The purpose of the current study was to evaluate the effect of AI on vascular injury as assessed by peripheral endothelial function among women with breast cancer. Methods: This is an observational, prospective study of 96 postmenopausal women with breast cancer at initiation of treatment, with or without AI. All participants underwent baseline and 6-12 months follow up non-invasive peripheral endothelial function measurement. Reactive hyperemia index (RHI) was measured using the EndoPAT test. The primary endpoint was endothelial function deterioration of at least 20% between baseline and follow-up. Results: Mean age of the study population was 66±7 years. There was no statistical difference in demographic data between the groups. Compared with the control group, more women in the treatment group demonstrated worsening of RHI (53% vs. 42%, p = 0.207) between baseline and 6-12 month follow up measurement. There was no statistical difference between the groups at baseline. When RHI deterioration was evaluated as a dichotomous variable, with a 20% cutoff, women in the AI group demonstrated higher rates of RHI deterioration (28% vs. 8%, p=0.020). The risk of AIs for endothelial dysfunction was correlated with burden of cardiovascular (CV) risk, such that in women with &gt;3 CV risk factors, AIs were associated with increased risk of RHI deterioration (42% vs. 10%, p=0.016), whereas in women with &lt;2 CV risk factors, rates of RHI deterioration were similar in AI and control groups (20% vs. 7%, p = 0.232). Conclusions: This study suggests that AI therapy may be associated with vascular injury as detected by deterioration in endothelial function. The effect is more pronounced among women with higher baseline CV risk factor burden. The results of this study have potentially important implications for patients with breast cancer being treated with AI and for women at increased lifetime risk of breast cancer who may use AI for breast cancer risk reduction. Clinical trial information: NCT00719966.

Noncardiovascular deaths are more common than cardiovascular deaths in patients with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: Insights from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial

Patients with impaired glucose tolerance have an elevated risk of cardiovascular (CV) death; however, the causes and risk factors associated with non-CV deaths are poorly understood. The NAVIGATOR trial enrolled 9,306 participants with impaired glucose tolerance and CV disease or at high CV risk, with a median follow-up of 6.4years. Using this population, we identified (1) the proportion of deaths attributed to CV, non-CV, and unknown causes, and (2) the risk factors associated with non-CV death. During the NAVIGATOR trial follow-up, 622 patients died. Investigators reported 244 (39.2%) CV deaths, 313 (50.3%) non-CV deaths, and 65 (10.5%) deaths of unknown cause. Myocardial infarction was the leading cause of investigator-reported death (57/622 [9.2%]). Among non-CV deaths, the most commonly identified cause related to malignancy (177/313 [56.5%]). Using adjudicated causes of death, Cox proportional hazard models identified 3 independent prognostic markers that increased the risk of non-CV death: history of non-melanoma skin cancer (hazard ratio 2.67 [95% CI 1.65-4.33]; P<.0001), white blood cell count (1 unit >5000/mm3; 1.10 [1.02-1.18]; P=.011), and serum potassium levels (per 1mmol/L above any value; 1.67 [1.302.15]; P<.0001). Despite the high baseline CV risk among patients in the NAVIGATOR trial, the most common cause of death was non-CV. The high burden of non-CV death in this population has potential implications for future CV event-driven trials.