Risk Of Adverse Cardiovascular Outcomes Research Articles

Safety and Efficacy of Anti-Hypertensive Medications in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis.

Hypertension (HTN) is a co-morbidity that is commonly associated with heart failure with preserved ejection fraction (HFpEF). However, it remains unclear whether treatment of hypertension in HFpEF patients is associated with improved cardiovascular outcomes. The purpose of this meta-analysis is to evaluate the association of anti-hypertensive medical therapy with cardiovascular outcomes in patients with HFpEF. We performed a database search for studies reporting on the association of anti-hypertensive medications with cardiovascular outcomes and safety endpoints in patients with HFpEF. The databases searched include OVID Medline, Web of Science, and Embase. The primary endpoint was all-cause mortality. Secondary endpoints include cardiovascular (CV) mortality, worsening heart failure (HF), CV hospitalization, composite major adverse cardiovascular events (MACE), hyperkalemia, worsening renal function, and hypotension. A total of 12 studies with 14062 HFpEF participants (7010 treated with medical therapy versus 7052 treated with placebo) met inclusion criteria. Use of anti-hypertensive medications was not associated with lower all-cause mortality, CV mortality or CV hospitalization compared to treatment with placebo (OR 1.02, 95% CI 0.77-1.35; p=0.9, OR 0.88, 95% CI 0.73-1.06; p=0.19, OR 0.99, 95% CI 0.87-1.12; p=0.83, OR 0.90, 95% CI 0.79-1.03; p=0.11). Anti-hypertensive medications were not associated with lower risk of subsequent acute myocardial infarction (AMI) (OR 0.53, 95% CI 0.07-3.73; p=0.5). Use of anti-hypertensive medications was associated with a statistically significant lower risk of MACE (OR 0.90, 95% CI 0.83-0.98; p=0.02). While treatment with anti-hypertensive medications was not associated with lower risk of all-cause mortality, their use may be associated with reduce risk of adverse cardiovascular outcomes in patients with HFpEF regardless of whether they have HTN. Additional high quality studies are required to clarify this association and determine the effect based on specific classes of medications.

Cold-water foot immersion and physiological strain of adults with coronary artery disease during hot and humid heat exposure

Introduction: Heat extremes are associated with a greater risk of adverse cardiovascular outcomes, especially among adults with coronary artery disease. While air-conditioning provides exceptional protection during heat extremes, it is neither sustainable nor widely accessible. Cold-water foot immersion reduces physiological heat strain in healthy young adults but its effect in more vulnerable populations remains unknown. Objective and hypotheses: This study aims to identify the effect of cold-water foot immersion on markers of physiological heat strain in adults with coronary artery disease. We hypothesized that cold-water foot immersion would reduce physiological heat strain when used on its own and that this effect would be greater when combined with an electric fan. Methods: 17 adults living with stable coronary artery disease (2 females/15 males; 67±8 years) were exposed to a 38°C, 60% relative humidity environment for 3 hours on three separate, randomized occasions: i) no cooling (control; CON); ii) cold-water foot immersion (20 min of immersion each 30 min, ~30 cm in water kept at ~18°C; FI); iii) cold-water foot immersion and fan use (FI+FAN). Rectal and skin temperatures, heart rate (5-lead ECG), and whole-body sweat loss (change in nude weight) were measured. Results: The increase in rectal temperature did not differ between conditions (CON: 0.40±0.24°C, FI: 0.41±0.29°C, and FI+FAN: 0.36±0.22°C; p≥0.49). The increase in skin temperature was reduced with FI and FI+FAN compared to CON (CON: 4.9±0.8°C, FI: 4.1±1.2°C, and FI+FAN: 4.3±0.8°C; p≤0.01), with no difference between FI and FI+FAN (p=0.15). Similarly, the increase in heart rate was reduced with FI and FI+FAN compared to CON (CON: 8±6 bpm, FI: 4±6 bpm, and FI+FAN: 3±6 bpm; p≤0.01), with no difference between FI and FI+FAN (p=0.45). Sweat loss was also reduced by FI and FI+FAN compared with CON (CON: 823±114 g, FI: 544±174 g, and FI+FAN: 671±255 g; p≤0.03), with sweat loss during FI sweat loss being lower than during FI+FAN (p=0.03). Conclusion: The results show that cold-water foot immersion, used alone or in combination with an electric fan, reduces the increase in heart rate and whole-body sweat loss of adults living with coronary artery disease exposed to a hot and humid environment for 3 hours. This could be linked to the lower increase in skin temperature with foot immersion. National Health and Medical Research Council of Australia (APP1147789). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease.

Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Continuous glucose monitoring for glycaemic control and cardiovascular risk reduction in patients with type 2 diabetes not on insulin therapy: A clinical trial.

To evaluate the impact of the Dexcom G6 continuous glucose monitoring (CGM) device on glycaemic control and cardiometabolic risk in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk who are not on insulin therapy. Adults with T2DM with glycated haemoglobin (HbA1c) >7% and body mass index (BMI) ≥30 kg/m2 not using insulin were enrolled in a two-phase cross-over study. In phase 1, CGM data were blinded, and participants performed standard glucose self-monitoring. In phase 2, the CGM data were unblinded, and CGM, demographic and cardiovascular risk factor data were collected through 90 days of follow-up and compared using paired tests. Forty-seven participants were included (44% women; 34% Black; mean age 63 years; BMI 37 kg/m2; HbA1c 8.4%; 10-year predicted atherosclerotic cardiovascular disease risk 24.0%). CGM use was associated with a reduction in average glucose (184.0 to 147.2 mg/dl, p < .001), an increase in time in range (57.8 to 82.8%, p < .001) and a trend towards lower glucose variability (26.2 to 23.8%). There were significant reductions in HbA1c, BMI, triglycerides, blood pressure, total cholesterol, diabetes distress and 10-year predicted risk for atherosclerotic cardiovascular disease (p < .05 for all) and an increase in prescriptions for sodium-glucose cotransporter 2 inhibitors (36.2 to 83.0%) and glucagon-like peptide-1 receptor agonists (42.5 to 87.2%, p < .001 for both). Dexcom G6 CGM was associated with improved glycaemic control and cardiometabolic risk in patients with T2DM who were not on insulin. CGM can be a safe and effective tool to improve diabetes management in patients at high risk for adverse cardiovascular outcomes.

Association between habitual betel quid chewing and risk of adverse cardiovascular outcomes: A systematic review.

Habitual betel quid chewing, a tobacco product, is a leading cause of oral cancer in Asia-Pacific countries where this practice is most prevalent. However, it is not well understood whether betel quid chewing is also a cause of adverse cardiovascular outcomes. To address this gap, we conducted a systematic literature review of peer-reviewed published studies evaluating the association between habitual betel quid use on the risk of adverse cardiovascular outcomes. We searched PubMed for studies assessing the correlation between betel quid chewing and cardiovascular health. We included studies if (i) they included human subjects; (ii) were peer-reviewed articles in indexed journals; and (iii) were in English. We extracted data from eligible studies and stratified them by geographical location, study designs and cardiovascular outcomes. Finally, we did a narrative synthesis of the data to identify adverse cardiovascular outcomes associated with chronic betel quid use. We reviewed data from 19 studies that met the inclusion criteria. Habitual betel quid chewing was associated with hypertension, atherosclerosis, inflammation and ischaemic heart disease. In addition, betel quid use was a risk factor for arrhythmias. Interestingly, betel quid use was an independent risk factor for cardiovascular disease in women. Long-term betel quid consumption was associated with higher risks for all-cause mortality and increased overall cardiovascular risk. Habitual betel quid chewing is an important cardiovascular risk factor in populations where the practice is prevalent.

Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention

BackgroundSince the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI.MethodsThis single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α.ResultsUnadjusted Kaplan–Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28–5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12–5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively).ConclusionThe study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI.Trial registration: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians’ Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan—Clinical Trials Registry, UMIN-CTR 000035587).

Risk Factors and Adverse Outcomes of Hypoglycemia in Older Patients with Type 2 Diabetes Mellitus

Currently, the world is experiencing a steady increase in the number of patients with type 2 diabetes mellitus (T2DM); this disease is recognized as a global medical and social problem of the 21st century. There is also a trend towards increasing life expectancy and, as a result, an aging population. Accordingly, the number of older patients with T2DM is increasing. Hypoglycemia, a serious complication of T2DM, is quite common among this category of patients. Hypoglycemia leads to worsening glycemic control, cognitive deficits, and an increased risk of adverse cardiovascular outcomes in older patients. This review examines the risk factors for hypoglycemic conditions that must be taken into account when prescribing glucose-lowering therapy to older patients and their prognostic significance in assessing the risk of hypoglycemia. The possible negative consequences of hypoglycemia are described and the importance of individual goals for glycemic control in older patients is emphasized.

Dapagliflozin in patients with heart failure and previous myocardial infarction: A participant-level pooled analysis of DAPA-HF and DELIVER.

Patients with heart failure (HF) and history of myocardial infarction (MI) face a higher risk of disease progression and clinical events. Whether sodium-glucose cotransporter 2 inhibitors may modify clinical trajectory in such individuals remains incompletely understood. The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with left ventricular ejection fraction (LVEF) ≤40% and > 40%, respectively. In this pooled participant-level analysis, we assessed efficacy and safety outcomes by history of MI. The primary outcome in both trials was the composite of cardiovascular death or worsening HF. Of the total of 11 007 patients, 3731 (34%) had a previous MI and were at higher risk of the primary outcome across the spectrum of LVEF in covariate-adjusted models (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.02-1.24). Dapagliflozin reduced the risk of the primary outcome to a similar extent in patients with (HR 0.83, 95% CI 0.72-0.96) and without previous MI (HR 0.76, 95% CI 0.68-0.85; pinteraction = 0.36), with consistent benefits on key secondary outcomes as well. Serious adverse events did not occur more frequently with dapagliflozin, irrespective of previous MI. History of MI confers increased risks of adverse cardiovascular outcomes in patients with HF across the LVEF spectrum, even among those with preserved ejection fraction. Dapagliflozin consistently and safely reduces the risk of cardiovascular death or worsening HF, regardless of previous MI.

Child Marriage and Cardiovascular Risk: An Application of the Non-laboratory Framingham Risk Score.

Child marriage, defined as marriage before the age of 18 years, is a precocious transition from adolescence to adulthood, which may take a long-term toll on health. This study aims to assess whether child marriage was associated with added risk of adverse cardiovascular outcomes in a nationally representative sample of Indian adults. Applying the non-laboratory-based Framingham algorithm to data on 336,953 women aged 30-49 years and 49,617 men aged 30-54 years, we estimated individual's predicted heart age (PHA). Comparing the PHA with chronological age (CA), we categorized individuals in four groups: (i) low PHA: PHA < CA, (ii) equal PHA: PHA = CA (reference category), (iii) high PHA: PHA > CA by at most 4 years, and (iv) very high PHA: PHA > CA by 5 + years. We estimated multivariable multinomial logistic regressions to obtain relative risks of respective categories for the child marriage indicator. We found that women who were married in childhood had 1.06 (95% CI 1.01-1.10) and 1.22 (95% CI 1.16-1.27) times higher adjusted risks of having high and very high PHA, respectively, compared to women who were married as adults. For men, no differential risks were found between those who were married as children and as adults. These results were generally robust across various socioeconomic sub-groups. These findings add to the relatively new and evolving strand of literature that examines the role of child marriage on later life chronic health outcomes and provide important insights for public health policies aimed at improving women's health and wellbeing.

Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis.

The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Comparative effectiveness of moderate-intensity statin with ezetimibe therapy versus high-intensity statin monotherapy in patients with acute coronary syndrome: a nationwide cohort study

The long-term outcome of first-line moderate-intensity statin with ezetimibe combination therapy for secondary prevention after percutaneous coronary intervention in patients with acute coronary syndrome (ACS) compared to high-intensity statin monotherapy remains elusive. The objective of this study was to compare the effectiveness of moderate-intensity statin and ezetimibe combination therapy with high-intensity statin monotherapy. We conducted a nationwide, population-based, retrospective, cohort study of patients with ACS from 2013 to 2019. The patients using combination therapy were matched (1:1) to those using monotherapy. The primary outcome was a composite of myocardial infarction, stroke and all-cause mortality. We estimated the hazard ratios (HR) and 95% confidence intervals (CIs) using the Cox proportional hazards regression. After propensity score matching, 10,723 pairs were selected. Men accounted for 70% of the patients and 37% aged > 70 years. The primary endpoint occurred in 1297 patients (12.1%) in the combination group and in 1426 patients (13.3%) in the monotherapy group, and decreased risk (HR 0.85, 95% CI 0.78–0.92, P < 0.001) in the combination group. Among the patients with ACS, moderate-intensity statin with ezetimibe combination therapy was associated with decreased risk of adverse cardiovascular outcomes compared with high-intensity statin monotherapy in a nationwide population-based study representing routine clinical practice.

Psychological Distress and the Risk of Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease

BackgroundPsychological distress is a recognized risk factor in patients with coronary heart disease (CHD), but its clinical significance is unclear. ObjectivesThe purpose of this study was to determine if an index of psychological distress is independently associated with adverse outcomes and significantly contributes to risk prediction. MethodsPooled analysis of 2 prospective cohort studies of patients with stable CHD (N = 891). A psychological distress score was constructed using measures of depression, anxiety, anger, perceived stress, and post-traumatic stress disorder, measured at baseline. The study endpoint included cardiovascular death or first or recurrent nonfatal myocardial infarction or hospitalization for heart failure at 5.9 years. ResultsIn both cohorts, first and recurrent events occurred more often among those in the highest tertile of distress score than those in the lowest tertile. After combining the 2 cohorts, compared with the lowest tertile, the hazards ratio for having a distress score in the highest tertile was 2.27 (95% CI: 1.69-3.06), and for the middle tertile, it was 1.52 (95% CI: 1.10-2.08). Adjustment for demographics and clinical risk factors only slightly weakened the associations. When the distress score was added to a traditional clinical risk model, C-statistic, net reclassification index, and integrative discrimination index all significantly improved. ConclusionsAmong patients with CHD, a composite measure of psychological distress was significantly associated with an increased risk of adverse events and significantly improved risk prediction.

NON-DIPPING BLOOD PRESSURE PATTERNS AND ASSOCIATED TARGET ORGAN DAMAGE IN ELDERLY HYPERTENSIVE PATIENTS

Background: Older adults with hypertension face an increased risk of adverse cardiovascular outcomes, emphasizing the importance of target organ damage (TOD) in their treatment. The non-dipping blood pressure (BP) pattern, characterized by inadequate reduction of nocturnal BP (less than 10-20%), is associated with a higher likelihood of TOD in individuals with essential hypertension. This study aimed to examine the characteristics of non-dipping BP patterns among elderly individuals with essential hypertension and evaluate their associations with TOD. Methods: A descriptive cross-sectional study was conducted, involving 96 patients aged ≥60 years (mean age 70.9 ± 7.9 years, 35.4% male). Participants underwent routine clinical and laboratory assessments, including clinic and 24-hour ambulatory blood pressure monitoring. TOD was defined as the presence of left ventricular (LV) hypertrophy, renal impairment, or proteinuria. Results: Non-dipping patterns for systolic and diastolic BP were observed in 36 (36.5%) and 41 (42.7%) patients, respectively. TOD was present in 61 (63.5%) patients. Non-dipping systolic patients exhibited lower rates of diabetes mellitus (37.1% vs. 81.3%, p=0.006), dyslipidemia (68.6% vs. 100%, p=0.011), higher levels of creatinine (median 85.6, interquartile range [IQR] 72.1-101 vs. 70.8, IQR 62.4-78.3 µmol/l, p=0.012), and higher LV mass index (median 106.6, IQR 96.4-148.4 vs. 93.7, IQR 72.9-111.5 g/m2, p=0.028) compared to dipping patients. Non-dipping diastolic patients had a lower prevalence of dyslipidemia (73.2% vs. 100%, p=0.048) and a lower body mass index (median 23, IQR 19.73-25 vs. 25.26, IQR 22.54-27.17 kg/m2, p=0.013). Multivariate analysis, after adjusting for cardiovascular risk, showed that non-dipping patterns (both systolic and diastolic) were associated with TOD (odds ratio 7.21; 95% confidence interval 1.47-35.36, p=0.015). Conclusion. Our study underscores the significant association between non-dipping blood pressure patterns and TOD in elderly individuals with essential hypertension. The notable prevalence of non-dipping patterns emphasizes the clinical importance of monitoring and managing these patterns in clinical practice.

Pharmacist impact on evidence-based prescribing of diabetes medications in patients with clinical atherosclerotic cardiovascular disease.

Including pharmacists on care teams of patients with type 2 diabetes (T2D) has been shown to promote guideline-based prescribing and improve glycemic control, lowering risks of adverse cardiovascular outcomes. Evidence is lacking regarding whether including pharmacists on the care team is associated with the prescribing of GLP-1 receptor agonists (GLP-1 RA) and SGLT-2 inhibitors (SGLT-2i) recommended for use in patients with T2D and atherosclerotic cardiovascular disease (ASCVD). To assess the association between having a pharmacist on the primary care team of patients with T2D and ASCVD and being prescribed a guideline-recommended GLP-1 RA or SGLT-2i. A cross-sectional analysis of patients with T2D and ASCVD seen by primary care providers at an academic medical center between June 2019 and May 2020 was completed. Patients with prescriptions for GLP-1 RA or SGLT-2i with evidence of cardiovascular benefit were identified and compared between those with pharmacist care vs usual care using multivariable log-binominal regression analyses. Of 1,497 included patients, 1,283 (85.7%) were in the usual care group (mean age 68.9 years, hemoglobin A1c 7.6%) and 214 (14.3%) in the pharmacist care group (mean age 64.5 years, A1c 9.0%). Of the pharmacist care group, 50.5% were prescribed a GLP-1 RA or SGLT-2i with cardiovascular benefit vs 17.9% in the usual care group (P < 0.001). In multivariable analyses controlling for A1c and other potential confounders, those in the pharmacist care group were 2.15 times as likely to have been prescribed a GLP-1 RA or SGLT-2i than those in the usual care group (adjusted risk ratio 2.15, 95% CI = 1.83-2.52; P < 0.001). These data provide preliminary evidence that integrating pharmacists into patient care teams is associated with increased prescribing of guideline-recommended treatment with GLP-1 RA and SGLT-2i in patients with T2D and ASCVD, yet there is room for improvement in prescribing these agents to patients with T2D and ASCVD.

Impact of Baseline Comorbidities and Treatment on Cardiovascular (CV) Outcomes in Patients with Chronic Lymphocytic Leukemia (CLL): Results of a Systematic Literature Review (SLR) of Interventional Trials and a Targeted Literature Review (TLR) of Real-World Observational Studies in CLL

Background: Ibrutinib, the first Bruton tyrosine kinase inhibitor (BTKi) indicated for CLL, has been associated with a higher risk of CV events, including atrial fibrillation (AF) and hypertension, vs non-BTKi active comparators and placebo. In a phase 3 clinical trial of patients (pts) with CLL comparing ibrutinib with acalabrutinib-a more selective, second-generation BTKi-CV event incidence was numerically higher with ibrutinib and the incidence and cumulative risk of AF were significantly higher with ibrutinib (Byrd JC et al. J Clin Oncol. 2021;39:3441-52). Ibrutinib's toxicity profile prompted changes to its prescribing information and lowered its recommendation status in current CLL guidelines. We conducted an SLR of interventional trials in CLL followed by a supplemental TLR of observational studies in CLL to explore the extent to which CV outcomes of pts with CLL are driven by their baseline comorbidities or treatments. Methods: Embase and MEDLINE were searched to identify evidence in peer-reviewed journals (cutoff date: June 23, 2023). For the SLR, limits were English articles published in 2012 or later, and inclusion criteria specified phase 2/3 interventional trials in adults aged ≥18 y with treatment-naive or relapsed/refractory CLL. Treatments included BTKis, BCL-2 inhibitors, and chemoimmunotherapy. CV outcomes were arrhythmia, heart failure, major adverse CV events, major bleeding, myocardial infarction, stroke, sudden cardiac death, and venous thromboembolism. For the TLR, language and time limits were analogous to the SLR. Additional limits were observational studies with &amp;gt;70% CLL pts receiving any or no treatment. The TLR assessed baseline CV events/risk, including arrhythmia, heart failure, major adverse CV events, major bleeding, myocardial infarction, stroke, sudden cardiac death, and venous thromboembolism. Results: The SLR yielded 55 studies. Among the phase 3 randomized controlled trials, incidence ranges were 0%-16% for AF/atrial flutter, 0%-6.9% for heart failure, and 0%-11% for major bleeding; rates were generally higher with BTKis, among which ibrutinib appeared to be associated with the highest rates ( Figure 1). CV data from the SLR were sparse and heterogeneous, primarily due to limited baseline CV risk reporting and substantial variability in CV adverse event reporting. To clarify relationships of CV risk with treatment, we performed the TLR, which yielded 24 studies. Analysis of baseline CV risk reported in the observational studies yielded several key findings ( Figure 2): 1) in pts with CLL, the risk of CV events, including AF, increased with age; in pts aged 65−74 y and ≥65 y, the reported risk of AF was 2.4-fold and 2.8-fold higher, respectively, than that of pts aged &amp;lt;65 y (Shanafelt TD et al. Leuk Lymphoma. 2017;58:1630-9; Visentin A et al. Hematol Oncol. 2019;37:508-12); 2) baseline CV risk was similarly high in pts with CLL and matched non-CLL comparators (Larsson K et al. Am J Hematol. 2022;97:E255-7); 3) ibrutinib was associated with a higher risk of CV disease relative to chemotherapy, even when prior AF, age, and anticoagulant exposure were controlled for (Abdel-Qadir H et al. J Clin Oncol. 2021;39:3453-62). In ibrutinib-treated pts with a B-cell malignancy followed in cardio-oncology clinics (N=53; n=38 CLL), median time to new onset of ibrutinib-related AF was 5.5 mo; AF incidence was 15-fold higher in ibrutinib-treated pts overall vs that expected in an age- and sex-comparable general population and in ibrutinib-treated pts with CLL vs that expected in pts with CLL and no ibrutinib treatment (Baptiste F et al. Open Heart. 2019;6:e001049). Conclusions: CLL primarily affects the elderly, who are at higher risk of CV events vs a younger demographic. Results suggest that some pts with CLL have an increased risk of adverse CV outcomes; thus, it would be inaccurate to attribute the higher rates of CV events observed in pts with CLL solely to their treatment as it is plausible that pts with CLL already have an elevated CV risk contributing to such outcomes. However, our findings suggest that the first-generation BTKi (ibrutinib) may impact CV outcomes in these pts; data examining the CV risk of second-generation BTKis and other novel therapies (eg, venetoclax) are limited. Future research that consistently estimates baseline CV risk and closely monitors CV parameters in pts with CLL is required to ascertain the true risk of CV disease due to CLL treatment.

Cardiovascular Outcomes of α-Blockers vs 5-α Reductase Inhibitors for Benign Prostatic Hyperplasia

The most prescribed class of medications for benign prostatic hyperplasia (BPH) is α-blockers (ABs). However, the cardiovascular safety profile of these medications among patients with BPH is not well understood. To compare the safety of ABs vs 5-α reductase inhibitors (5-ARIs) for risk of adverse cardiovascular outcomes. This active comparator, new-user cohort study was conducted using insurance claims data from a 20% random sample of Medicare beneficiaries from 2007 to 2019 to evaluate the 1-year risk of adverse cardiovascular outcomes. Males aged 66 to 90 years were indexed into the cohort at new use of an AB or 5-ARI. Twelve months of continuous enrollment and at least 1 diagnosis code for BPH within 12 months prior to initiation were required. Data were analyzed from January 2007 through December 2019. Exposure was defined by a qualifying prescription fill for an AB or 5-ARI after at least 12 months without a prescription for these drug classes. Follow-up began at a qualified refill for the study drug. Primary study outcomes were hospitalization for heart failure (HF), composite major adverse cardiovascular events (MACE; hospitalization for stroke, myocardial infarction, or death), composite MACE or hospitalization for HF, and death. Inverse probability of treatment and censoring-weighted 1-year risks, risk ratios (RRs), and risk differences (RDs) were estimated for each outcome. Among 189 868 older adult males, there were 163 829 patients initiating ABs (mean [SD] age, 74.6 [6.2] years; 579 American Indian or Alaska Native [0.4%], 5890 Asian or Pacific Islander [3.6%], 9179 Black [5.6%], 10 610 Hispanic [6.5%], and 133 510 non-Hispanic White [81.5%]) and 26 039 patients initiating 5-ARIs (mean [SD] age, 75.3 [6.4] years; 76 American Indian or Alaska Native [0.3%], 827 Asian or Pacific Islander [3.2%], 1339 Black [5.1%], 1656 Hispanic [6.4%], and 21 605 non-Hispanic White [83.0%]). ABs compared with 5-ARIs were associated with an increased 1-year risk of MACE (8.95% [95% CI, 8.81%-9.09%] vs 8.32% [95% CI, 7.92%-8.72%]; RR = 1.08 [95% CI, 1.02-1.13]; RD per 1000 individuals = 6.26 [95% CI, 2.15-10.37]), composite MACE and HF (RR = 1.07; [95% CI, 1.03-1.12]; RD per 1000 individuals = 7.40 [95% CI, 2.88-11.93 ]), and death (RR = 1.07; [95% CI, 1.01-1.14]; RD per 1000 individuals = 3.85 [95% CI, 0.40-7.29]). There was no difference in risk for HF hospitalization alone. These results suggest that ABs may be associated with an increased risk of adverse cardiovascular outcomes compared with 5-ARIs. If replicated with more detailed confounder data, these results may have important public health implications given these medications' widespread use.

Prevalence of traditional cardiovascular risk factors in subjects with unrecognized myocardial infarction: a systematic review and meta-analysis

Abstract Background Unrecognized myocardial infarction (UMI) is defined as myocardial ischemia (MI) that was not recognized as such during the acute phase, but later identified by pathological Q waves on an electrocardiogram (ECG), myocardial imaging evidence, or pathological findings on autopsy. Previous studies found that UMI accounts for up to 50% of all MIs, especially in women and the elderly. UMI is associated with increased risk of adverse cardiovascular outcomes and mortality, similar to subjects with recognized myocardial infarction (RMI). However, associated risk factors of UMI remain understudied. Purpose We aimed to summarize and combine the evidence on the associations between traditional cardiovascular risk factors and UMI in the general population. We also sought to assess sex differences in these risk factors. Methods A systematic search of general population-based cohort studies investigating UMI and reporting traditional cardiovascular risk factors of subjects with UMI and subjects without MI was performed through Embase, Medline, and Google Scholar up to 7 February 2023. Study selection, data extraction and risk of bias were assessed independently by 2 authors. Pooled standardized mean differences (SMD) or odds ratios (ORs) with 95% confidence intervals (CI) of traditional cardiovascular risk factors were determined, comparing UMI to subjects without MI. Random-effects meta-analyses were performed. If data allowed, analyses were repeated stratified by sex. Results A total of 17 studies were included involving 216,858 individuals, among which 4,717 experienced UMI (mean age 66.1±8.3 year, 49% women). UMI was diagnosed through ECG in 14 studies and MRI in 3 studies. All studies established diagnosis of UMI and risk factors in a cross-sectional manner. Compared to subjects without MI, individuals with UMI demonstrated significantly larger values of BMI (SMD 0.05, 95% CI 0.03-0.08) and SBP (SMD 0.25, 95% CI 0.12-0.39), and higher prevalence of hypertension (OR 1.71, 95% CI 1.07-2.72) and diabetes mellitus (DM) (OR 1.81, 95% CI 1.40-2.34). Risk factors were reported stratified by sex in 3 studies. The relation between hypertension and UMI was stronger in women than in men. In contrast, the association of DM with UMI was weaker in women. However, these differences were statistically non-significant. Conclusion BMI, SBP, hypertension and diabetes mellitus are associated with an increased risk of UMI, similar to RMI. Limited evidence from studies stratified for sex indicate a differential impact of traditional risk factors on UMI in women and men.

Comparison of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in myocardial infarction patients with type 2 diabetes

Abstract Background Both sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to reduce the risk of adverse cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients with established atherosclerotic cardiovascular disease. Purpose The aim of this study was to assess the comparative effectiveness of SGLT2i and GLP1-RA in myocardial infarction (MI) patients with T2DM. Methods This observational cohort study included MI patients with T2DM who were treated with SGLT2i or GLP1-RA within 180 days of hospital discharge between 2013 and 2021. Data was acquired from the SWEDEHEART registry, a nationwide quality register. The co-primary endpoints of this study were a composite of MI, ischemic stroke and all-cause mortality (MACE) and a composite of heart failure hospitalisation (HHF) and all-cause mortality. Inverse probability of treatment weighting was used to adjust for differences in baseline covariates between the treatment groups. Results This study consisted of 617 patients who were treated with SGLT2i and 543 patients who were treated with GLP1-RA. We observed no statistically significant differences between SGLT2i and GLP1-RA concerning the risk of MACE (adjusted incidence rate 76 vs. 68 events per 1000 person-years; HR 1.09 [95% CI 0.85 - 1.40]) and the risk of HHF or all-cause mortality (adjusted incidence rate 52 vs. 50 events per 1000 person-years; HR 1.04 [95% CI 0.80 - 1.36]). Similarly, we did not observe any statistically significant differences between the treatment groups concerning the secondary outcomes of MI (adjusted incidence rate 63 vs. 53 events per 1000 person-years; HR 1.08 [95% CI 0.83 - 1.40]), stroke (adjusted incidence rate 7 vs. 6 events per 1000 person-years; HR 1.22 [95% CI 0.57 - 2.87]), HHF (adjusted incidence rate 45 vs. 38 events per 1000 person-years; HR 1.06 [95% CI 0.80 - 1.41]) and all-cause mortality (adjusted incidence rate 11 vs. 15 events per 1000 person-years; HR 1.06 [95% CI 0.63 - 1.82]). Conclusions There were no statistically significant differences between SGLT2i and GLP1-RA concerning the risk of recurrent ischemic events, HHF and all-cause mortality in this cohort of MI patients with T2DM.Cumulative incidence of events

Abstract 18437: Efficacy and Safety of Dapagliflozin in Patients With Heart Failure and Previous Myocardial Infarction

Introduction: Patients with HF and history of myocardial infarction (MI) may represent a distinct subpopulation with unique pathways of disease progression and elevated risk of clinical events. Whether SGLT2 inhibitors may modify disease trajectory in such individuals is uncertain. Methods: The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with LVEF ≤40% and &gt;40%, respectively. In this pooled participant-level analysis, we assessed efficacy and safety outcomes by history of MI. The primary outcome in both trials was the composite of cardiovascular (CV) death or worsening HF. Results: Of the total of 11,007 patients, 3,731 (34%) had a prior MI and were at higher risk of the primary outcome across the spectrum of LVEF in covariate-adjusted models (HR 1.12 [95% CI 1.02-1.24]; Left Panel ). Dapagliflozin reduced the risk of the primary outcome to a similar extent in patients with (HR 0.83 [95% CI 0.72-0.96]) and without prior MI (HR 0.76 [95% CI 0.68-0.85]; P i nteraction =0.36), with consistent benefits on key secondary outcomes as well ( Right Panel ). Serious adverse events did not occur more frequently with dapagliflozin, irrespective of prior MI. Conclusions: History of MI confers increased risks of adverse cardiovascular outcomes in patients with HF across the spectrum of ejection fraction. Dapagliflozin consistently and safely reduces the risk of adverse cardiovascular outcomes, regardless of previous MI. Ongoing trials are actively examining SGLT2 inhibitors when introduced early after acute MI.

Abstract 12734: A Sex-Stratified Analysis of Social Determinants of Health and Adverse Cardiovascular Outcomes in Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is associated with a heightened risk of adverse cardiovascular outcomes. Current prediction models often overlook potential sex differences, as well as the combined influence of gendered social determinants of health (SDOH) with traditional cardiovascular risk factors. The objective of this study is to compare the associations between social determinants and adverse outcomes in models stratified by sex. Methods: Participants were sourced from the EURObservational Research Programme-Atrial Fibrillation (ESC-EHRA EORP-AF) General Long-Term Registry. Alongside CHA 2 DS 2 -VASc variables, SDOH factors, including education, living arrangements, gender inequality index (GII), and EQ-5D-5L questionnaire subscales, were evaluated. The primary outcome was a composite of major adverse cardiovascular events (MACE) and all-cause mortality. We evaluated the predictive performance of various models using C-statistics, including individual CHA2DS2-VASc components, SDOH only, and a combined model. Results: Among 11,096 patients (mean age: 69.2 years; 40.7% females) from 27 European countries, sex-stratified analyses indicated fewer SDOH associations with composite outcomes in females compared to males. For both females and males, higher self-reported health and regular exercise were associated with lower risk of composite outcomes. In the male model only, a higher education level, higher GII, reduced mobility, reduced self-care ability, alcohol use, and smoking were all associated with an increased risk of MACE and all-cause mortality (Figure 1). The combined model demonstrated modest superior predictive performance, while the improvement when combining CHA2DS2-VASc and SDOH components appears more pronounced in males compared to females. Conclusions: The study highlights the distinct impact of SDOH in AF, with males exhibiting a wider range of SDOH factors associated with outcomes.