Cardio-Renal-Metabolic Multimorbidity in India: Findings from a Large Community-Based Study

Presenter: Sailesh Mohan, et al.

This large community-based study assessed the prevalence of Cardio-Renal-Metabolic Multimorbidity (CRMM) among 11,017 adults aged 30 years or older from North and South India. Data on sociodemographic characteristics, chronic diseases, and risk factors were collected through questionnaires, while blood pressure, anthropometric measurements, and fasting blood samples were obtained using standard methods. Cardio-Renal-Metabolic Multimorbidity was defined as the presence of at least two of the following conditions: diabetes, hypertension, cardiovascular disease, chronic kidney disease, and overweight/obesity. The mean age of participants was 49.1 years, and 53% were women. The overall prevalence of CRMM was 33.6% (95% confidence interval [CI]: 32.7–34.5), indicating that approximately one in three adults had multiple cardio-renal-metabolic conditions. Higher prevalence was observed among males (37.7%; 95% CI: 36.4–39.0), urban residents (42.9%; 95% CI: 41.6–44.3), individuals aged ≥60 years (49.7%; 95% CI: 47.8–51.7), and those in the highest wealth quintile (44.3%; 95% CI: 42.1–46.6).

These findings highlight the substantial burden of CRMM in India across different population groups. The authors suggest that integrated healthcare strategies targeting shared risk factors through primary care may help improve health outcomes associated with these interconnected conditions.

Lipid Management in Patients with High-Risk Diabetes Mellitus at Risk for a First Major Atherosclerotic Cardiovascular Event: Findings from the VESALIUS-REAL Global Study

Presenter: Mahendra Sibartie, et al.

This study evaluated lipid management practices in patients with high-risk diabetes mellitus (DM) who were at risk of experiencing their first major atherosclerotic cardiovascular event. Data were analyzed from 11 databases across North America, Europe, and the Asia-Pacific region between 2017 and 2022. High-risk DM was defined as diabetes with microvascular complications or chronic insulin use, along with elevated lipid levels and additional cardiovascular risk factors, but without a prior history of myocardial infarction or stroke. The analysis included 354,643 patients with high-risk DM, of whom 51% were women. Additionally, 14% had coronary artery disease, atherosclerotic cerebrovascular disease, or peripheral artery disease. Less than half of the patients (46%) were receiving lipid-lowering therapy (LLT) at the time they met study eligibility criteria. Among those receiving treatment, statin monotherapy was the most common regimen, accounting for 87% of LLT use. Among patients who were not receiving LLT at baseline, only 26% initiated treatment within one year. For patients already receiving LLT, treatment intensification within one year occurred in just 7% of cases. Lipid monitoring was also suboptimal, with only 42% of patients undergoing low-density lipoprotein cholesterol (LDL-C) testing during the first year of follow-up (n=149,495). Achievement of recommended LDL-C goals was low, with only 22% of patients reaching targets defined by local guidelines.

Overall, the findings indicate substantial gaps in lipid management among patients with high-risk DM, including low treatment rates, limited therapy intensification, inadequate lipid monitoring, and poor attainment of LDL-C goals.

Predictors of Therapeutic Inertia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

Presenter: Rachel Marie Perez, et al.

This post hoc analysis investigated the presence of therapeutic inertia (TI) in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, a multicenter study that enrolled approximately 10,000 participants with type 2 diabetes (T2D) and cardiovascular disease (CVD) or its risk factors. Participants were assigned to either intensive glycemic control (glycated hemoglobin [HbA1c] <6%) or standard glycemic control (HbA1c 7.0–7.9%). Despite protocol-defined treatment adjustment criteria, the study evaluated whether therapy was appropriately intensified when glycemic targets were not met. The analysis included 5,341 participants receiving insulin and covered 13,657 study visits. Therapeutic inertia was defined as failure to adjust insulin therapy or number of oral glucose-lowering agents despite HbA1c levels remaining above the treatment target for the assigned study arm. Across all visits, HbA1c was above target at 67% of encounters. Among these visits, therapeutic inertia was observed in 26% of cases, indicating that treatment was not intensified despite inadequate glycemic control. Age and sex were not associated with therapeutic inertia. Participants with higher HbA1c levels were less likely to experience therapeutic inertia compared with those with HbA1c levels of 8.0–8.9%. The likelihood of therapeutic inertia was lower in participants with HbA1c levels of 9.0–9.9% (odds ratio [OR] 0.53; 95% confidence interval [CI] 0.39–0.70) and HbA1c ≥10% (OR 0.64; 95% CI 0.42–0.97). In contrast, more frequent hypoglycemic events were associated with a greater likelihood of therapeutic inertia (OR 1.06; 95% CI 1.03–1.10 per additional weekly hypoglycemic event). Black participants were more likely to experience therapeutic inertia than other racial groups, with Black race remaining an independent predictor after adjustment for socioeconomic, clinical, and trial-related factors (OR 1.45; 95% CI 1.25–1.67).

Overall, therapeutic inertia was present even within a controlled clinical trial setting with predefined treatment protocols. Higher hypoglycemia frequency, Black race, and lower HbA1c levels were associated with a greater likelihood of therapeutic inertia.

Triple Target Achievement in Type 2 Diabetes

Presenter: Subhash Dalpat Sonawala, et al.

This cross-sectional study assessed whether achieving multiple metabolic targets was associated with a lower complication burden in 400 patients with type 2 diabetes mellitus (T2DM). Metabolic targets were defined as triglycerides <150 mg/dL, BMI 23–25, and HbA1c <7%. Patients were categorized based on the number of targets achieved: Group A (0–1 target), Group B (2 targets), and Group C (all three targets). Only 18% of patients achieved all three targets, while 45% achieved 0–1 target and 37% achieved 2 targets. The prevalence of multiple complications (≥2 of bone disease, neuropathy, or dyslipidemia) decreased with increasing target achievement, occurring in 68% of patients with 0–1 target and 42% of those with 2 targets. Achieving all three targets was associated with a 73% lower risk of multiple complications compared with achieving 0–1 target (relative risk [RR] 0.26; 95% confidence interval [CI] 0.14–0.49).Patients who met TG and BMI targets despite suboptimal HbA1c levels (7.2–8.1%) had fewer complications than those who achieved HbA1c <7% without meeting TG and BMI targets (28% vs 54%; p<0.01). Rates of osteoporosis (8% vs 32% vs 61%) and moderate-to-severe neuropathy (12% vs 38% vs 58%) also differed significantly across the groups (p<0.001 for both).

Overall, these findings suggest that achieving multiple metabolic targets is associated with a lower burden of diabetes-related complications than achieving glycemic targets alone.

Lipid Variability Is Associated with Incident Heart Failure and Elevation in NT-proBNP in the Multiethnic Study of Atherosclerosis

Presenter: Daniel S Nuyujukian, et al.

This study investigated whether visit-to-visit variability in lipid levels is associated with the risk of heart failure (HF) and elevated levels of N-terminal B-type natriuretic peptide (NT-proBNP), a marker of cardiac stress, in participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Lipid variability was assessed using the coefficient of variation for low-density lipoprotein cholesterol (CV-LDL) and log-transformed triglycerides (CV-logTrig). Participants with at least three lipid measurements before a heart failure event were included. Heart failure events were tracked for approximately 10 years. After adjustment for heart failure risk factors, greater variability in both triglycerides and low-density lipoprotein cholesterol was associated with a higher risk of heart failure. The hazard ratios were 1.47 (95% confidence interval [CI] 1.29–1.66) for CV-logTrig and 1.51 (95% CI 1.35–1.74) for CV-LDL (both p<0.001). Higher lipid variability was also associated with elevated NT-proBNP levels (>125 pg/mL) at follow-up. For CV-logTrig, the odds ratio (OR) was 1.09 (95% CI 1.01–1.18; p=0.03), while for CV-LDL it was 1.16 (95% CI 1.03–1.22; p=0.01). Associations were stronger for severely elevated NT-proBNP levels (>450 pg/mL), with ORs of 1.28 (95% CI 1.11–1.47; p<0.001) for CV-logTrig and 1.26 (95% CI 1.08–1.47; p=0.004) for CV-LDL.

These findings suggest that greater visit-to-visit variability in lipid levels is associated with an increased risk of heart failure and higher NT-proBNP levels, indicating a potential role of lipid variability in the early development of heart failure.

Revolutionizing Cardiac Health: Unlocking the Power of Oral Ketones to Boost Cardiac Efficiency, Changes in Insulin Secretion, and Cardiometabolic Outcomes

Authors: Francisca M. Acosta, et al.

Ketone infusion improves ejection fraction (EF) by approximately 6% within 3 hours in patients with T2D and HFrEF. Oral ketones (OKE) have demonstrated similar effects. This study evaluated the effects of chronic OKE ester administration (7 dayson cardiac function in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Twelve patients underwent cardiac magnetic resonance imaging and metabolic assessments at baseline, 3 hours after a single OKE dose, and after 7 days of twice-daily OKE treatment. Participants had a mean body mass index (BMI) of 31±1 kg/m², glycated hemoglobin (HbA1c) of 7.1±0.3%, and ejection fraction (EF) of 42±2% at baseline. OKE administration rapidly increased blood ketone levels to 6.0±0.3 mmol/L at 3 hours and was associated with an increase in EF of 5.9±0.9%. This improvement in cardiac function was maintained after 7 days of treatment. The study also observed increases in C-peptide and insulin levels following OKE administration, suggesting a possible insulin-stimulating effect of ketone bodies.

Overall, short-term OKE administration was well tolerated and was associated with improved cardiac efficiency which appears to be dose-dependent in patients with T2D and HFrEF. The findings also suggest potential insulinogenic effects of ketones, which require further investigation.

Cardiovascular Outcomes Associated with GLP-1 Receptor Agonist Use among Adults with Type 1 Diabetes and Overweight or Obesity: A Target Trial Emulation Using Real-World EHR Data

Authors: Yixue Shao, et al.

This target trial emulation study evaluated the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and cardiovascular outcomes in adults with type 1 diabetes (T1D) and overweight or obesity. Using electronic health records from the Epic COSMOS database, researchers compared 23,527 adults with T1D who initiated a GLP-1RA between 2020 and 2024 with 102,676 matched nonusers. The mean age of participants was 52.1 years, 55.9% were female, and 21% had pre-existing cardiovascular disease at baseline. The primary outcome was major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or all-cause mortality. GLP-1RA use was associated with a 31% lower risk of MACE compared with nonuse (hazard ratio [HR] 0.69; 95% confidence interval [CI]: 0.63–0.76; p<0.001). Significant reductions were also observed in the risk of atrial fibrillation (AF) (HR 0.82; 95% CI: 0.70–0.96) and heart failure (HF) (HR 0.83; 95% CI: 0.74–0.94). However, no significant association was found between GLP-1RA use and peripheral vascular disease (PVD) (HR 1.04; 95% CI: 0.94–1.16).

These data suggest the potential value of GLP-1RAs as a targeted therapeutic option for reducing macrovascular events in high-risk T1D populations, aligning with current standards of care in type 2 diabetes. 

Relative and Absolute Risk Reduction for MACE in Cardiovascular Outcomes Trials with GLP-1 Receptor Agonists in Female vs. Male People with Type 2 Diabetes

Authors: Young Hee Lee-Barkey, et al.

This pooled analysis evaluated whether the cardiovascular outcomes with glucagon-like peptide-1 receptor agonists (GLP-1RAs) differ between women and men with type 2 diabetes (T2D). Data were analyzed from eight cardiovascular outcomes trials (CVOTs), including LEADER, SUSTAIN-6, EXSCEL, HARMONY Outcomes, REWIND, PIONEER-6, AMPLITUDE-O, and SOUL. The analysis included 22,859 women (35.9%) and 40,803 men. Major adverse cardiovascular events (MACE) rates were compared between GLP-1RA and placebo groups, and results were normalized to a 3-year follow-up period. GLP-1RA treatment was associated with similar relative reductions in MACE risk in women (odds ratio [OR] 0.82; 95% confidence interval [CI], 0.75–0.89) and men (OR 0.86; 95% CI, 0.81–0.91). Absolute risk reductions were also comparable between women (1.66%; 95% CI, 1.45–1.87) and men (1.60%; 95% CI, 1.46–1.73). The number needed to treat (NNT) to prevent one MACE event was similar in women (60; 95% CI, 54–69) and men (63; 95% CI, 58–68). However, the baseline risk of MACE in the placebo group was higher in men than in women (4.3 vs. 3.3 events per 100 person-years of observation).

Overall, GLP-1 receptor agonists provided comparable reductions in major adverse cardiovascular events in women and men with type 2 diabetes, with similar absolute risk reductions and numbers needed to treat.

Relative and Absolute Risk Reduction for MACE in Cardiovascular Outcomes Trials with GLP-1 Receptor Agonists in Type 2 Diabetes Patients with and without ASCVD at Baseline

Authors: Michael Albrecht Nauck, et al.

This pooled analysis evaluated whether the cardiovascular outcomes with glucagon-like peptide-1 receptor agonists (GLP-1RAs) differ between patients with and without atherosclerotic cardiovascular disease (ASCVD) at baseline. Data were analyzed from seven cardiovascular outcomes trials: LEADER, SUSTAIN-6, EXSCEL, REWIND, PIONEER-6, AMPLITUDE-O, and SOUL. The analysis included 38,642 participants with ASCVD and 13,409 without ASCVD at baseline. Major adverse cardiovascular events (MACE) rates were compared between GLP-1RA and placebo groups, with results normalized to a 3-year follow-up period. GLP-1RAs produced similar relative reductions in MACE risk among participants with ASCVD (odds ratio [OR] 0.83; 95% confidence interval [CI], 0.78–0.88) and those without ASCVD (OR 0.89; 95% CI, 0.79–1.00). However, absolute risk reduction was significantly greater in participants with ASCVD than in those without ASCVD (2.12% vs. 0.92%). Accordingly, the number needed to treat (NNT) to prevent one MACE event was lower in the ASCVD group (47; 95% CI, 44–51) than without non-ASCVD group (109; 95% CI, 88–144). Participants receiving placebo had a higher baseline risk of MACE if they had ASCVD compared with those without ASCVD (4.7 vs. 3.0 events per 100 person-years of observation).

Overall, GLP-1 receptor agonists provided comparable relative reductions in major adverse cardiovascular events regardless of baseline ASCVD status; however, patients with established ASCVD experienced greater absolute risk reductions and lower numbers needed to treat.

Effect of Different Treatment Durations of Sodium-Glucose Cotransporter 2 Inhibitor on Cardiovascular Outcomes in Patients with Type 2 Diabetes: A Target Trial Emulation Study

Authors: Kyungyeon Jung, et al.

This nationwide South Korean study evaluated whether longer treatment duration with sodium-glucose cotransporter 2 inhibitors (SGLT2is) is associated with greater cardiovascular benefits in patients with type 2 diabetes. Using healthcare data from 2012 to 2023, researchers identified 1,174,088 patients with type 2 diabetes who initiated SGLT2i therapy. Participants were categorized according to treatment duration: less than 1 year, 1–2 years, 2–3 years, and 3 years or longer. The primary outcomes were major adverse cardiovascular events (MACE) and hospitalization for heart failure (HHF) over a 5-year follow-up period. The study population had a mean age of 57.3 years, and 40.5% were female. Compared with patients treated for less than 1 year, longer treatment durations were associated with progressively lower cardiovascular risk. For MACE, the risk ratios (RRs) were 0.93 (95% confidence interval [CI], 0.90–0.96) for 1–2 years of treatment, 0.82 (95% CI, 0.78–0.85) for 2–3 years, and 0.69 (95% CI, 0.67–0.72) for 3 years or longer. Similarly, the risk of HHF decreased with longer treatment duration, with RRs of 0.93 (95% CI, 0.90–0.97), 0.91 (95% CI, 0.80–0.99), and 0.74 (95% CI, 0.67–0.79), respectively.

Overall, longer persistence with SGLT2i therapy was associated with progressively greater reductions in the risk of major adverse cardiovascular events and hospitalization for heart failure, supporting the cardiovascular benefits of sustained treatment.

Evolocumab Reduces CV Events in Patients with High-Risk Diabetes: Results from the VESALIUS-CV Trial

Authors: Lawrence Leiter, et al.

This prespecified analysis of the Very Effective Strategy of LDL-C Assessment and Intervention Using Subcutaneous Evolocumab in Cardiovascular Risk Reduction (VESALIUS-CV) trial evaluated the effect of evolocumab on cardiovascular outcomes in patients with high-risk diabetes mellitus (HR-DM: microvascular disease, insulin use, or duration ≥10 years) who had no prior myocardial infarction or stroke for prevention of first CV events. The trial randomized patients with low-density lipoprotein cholesterol (LDL-C) levels >90 mg/dL and either atherosclerosis or HR-DM to receive evolocumab 140 mg every 2 weeks or placebo. The dual primary endpoints were coronary heart disease death, MI or ischemic stroke (3-P MACE) and 3-P MACE in addition to ischemia-driven arterial revascularization (4-P MACE).  Among the 12,257 participants enrolled, 6,002 (49%) had HR-DM. The median age was 66 years, 50% were female, 66% were receiving high-intensity statins, 24% were using sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1RAs), and 67% had no qualifying atherosclerosis. After a median follow-up of 4.6 years, evolocumab reduced the risk of 3-point major adverse cardiovascular events (MACE; coronary heart disease death, myocardial infarction, or ischemic stroke) by 29% compared with placebo in patients with HR-DM. In participants without HR-DM, the reduction was 21% (interaction p=0.47). Evolocumab also reduced the risk of 4-point MACE (3-point MACE plus ischemia-driven arterial revascularization) by 21% in the HR-DM group and by 18% in those without HR-DM (interaction p=0.73). The risk of myocardial infarction was reduced by 35–36% in both groups (interaction p=0.97). A numerically lower mortality rate was also observed with evolocumab in both subgroups. Among patients with HR-DM, the benefits of evolocumab were consistent regardless of the presence of atherosclerosis, baseline LDL-C levels, statin intensity, or use of SGLT2is or GLP-1RAs (all interaction p>0.05).

Overall, evolocumab reduced cardiovascular events in patients with HR-DM, including those without established atherosclerosis and those already receiving other cardioprotective therapies.

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