Saeid Mirzai

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline. Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance spectroscopy. The primary outcomes were ASCVD, HF, and all‐cause death. Secondary outcomes were myocardial infarction, ischemic stroke, peripheral artery disease, and CVD death. All outcomes were defined based on International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth Revision ( ICD‐10 ) codes. Multivariable‐adjusted Cox proportional hazards models examined the association of total KB with incident cardiovascular outcomes and mortality. Results: At a median follow‐up of 13.4 years, higher levels of total KB (per 10‐fold increase) were associated with a greater risk of incident ASCVD, HF, and all‐cause mortality (hazard ratio [HR], 1.31 [95% CI, 1.18–1.46], 1.44 [95% CI, 1.24–1.6]7, and 1.51 [95% CI, 1.38–1.66]), respectively. Participants also demonstrated a 37% (95% CI, 11%–69%) increased risk of stroke and 69% (95% CI, 43%–100%) increased risk of CVDdeath. There was no significant association between KB and incident myocardial infarction. Conclusions: Elevation in endogenous KB in a population free from CVD at baseline is associated with an increased risk of ASCVD, HF, stroke, and mortality.

Background: Insulin resistance (IR) and lipoprotein(a), Lp(a), are established contributors to cardiovascular disease (CVD) risk. Whether IR modifies the association between Lp(a) and CVD in primary prevention remains uncertain. Methods: This prospective cohort study included UK Biobank participants without baseline CVD. IR at enrollment was assessed using the triglyceride‐glucose index (TyG). The primary outcome was first major adverse cardiovascular event, defined as peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, or cardiovascular death. Cox models estimated adjusted hazard ratios (aHRs) with 95% CIs for log‐transformed Lp(a) and TyG, adjusting for each other. Lp(a) was categorized as P ‐value for the multiplicative interaction between TyG and Lp(a) was 0.07. Relative to reference, aHRs (95% CI) were 1.15 (1.10–1.20) for ≥125/low IR, 1.09 (1.06–1.12) for <125/high IR, and 1.32 (1.24–1.41) for ≥125/high IR. Conclusions: Lp(a) and IR each independently contribute to cardiovascular risk, with a combination offering improved risk stratification. This suggests that accounting for IR may enhance the assessment of Lp(a)‐associated risk in the context of primary CVD prevention setting.

Background/Objectives: The Metabolic Score for Insulin Resistance (METS-IR), a non-insulin-based index of insulin resistance (IR), and subclinical myocardial injury (SCMI), identified by electrocardiogram (ECG), are each associated with cardiovascular disease (CVD). However, their joint impact on mortality remains unclear. We examined the association of the METS-IR with SCMI and evaluated the individual and combined associations of SCMI and IR with cardiovascular mortality. Methods: We analyzed adults without baseline CVD from the Third National Health and Nutrition Examination Survey (1988–1994) with mortality follow-up through 31 December 2019. The METS-IR was calculated from fasting glucose, triglycerides, high-density lipoprotein cholesterol, and body mass index and categorized as low (<75th percentile) or high (≥75th percentile). SCMI was defined as a cardiac infarction injury score ≥ 10 on ECG. Multivariable logistic regression assessed associations between the METS-IR and SCMI, and Cox regression estimated cardiovascular mortality risk across SCMI-IR combinations. Results: Among 6079 participants, 14.1% had SCMI. Higher METS-IR values were associated with greater SCMI odds (OR (95% CI): 1.58 (1.31–1.90)). Over a median of 18.8 years, 563 (9.1%) cardiovascular deaths occurred. Both SCMI and high IR were individually associated with increased cardiovascular mortality ((HR (95% CI): 1.41 (1.19–1.69) and 1.32 (1.09–1.59), respectively). Participants with both SCMI and high IR had the highest risk (HR 1.92; 95% CI 1.49–2.50) compared with those with neither condition. Conclusions: In adults without prior CVD, the METS-IR was positively associated with SCMI. The coexistence of SCMI and high IR identified a subgroup at nearly twofold higher risk of cardiovascular mortality, supporting the combined use of ECG-based injury markers and metabolic indices for cardiovascular risk stratification.

Background/Objectives: The Metabolic Score for Insulin Resistance (METS-IR), a non-insulin-based index of insulin resistance (IR), and subclinical myocardial injury (SCMI), identified by electrocardiogram (ECG), are each associated with cardiovascular disease (CVD). However, their joint impact on mortality remains unclear. We examined the association of METS-IR with SCMI and evaluated the individual and combined associations of SCMI and IR with cardiovascular mortality. Methods: We analyzed adults without baseline CVD from the Third National Health and Nutrition Examination Survey. METS-IR was calculated from fasting glucose, triglycerides, high-density lipoprotein cholesterol, and body mass index and categorized as low (Results: Among 6,079 participants, 14.1% had SCMI. Higher METS-IR was associated with greater SCMI odds (OR(95%CI): 1.58(1.31-1.90)). Over a median of 18.8 years, 563 (9.1%) cardiovascular deaths occurred. Both SCMI and high IR were individually associated with increased cardiovascular mortality ((HR(95% CI): 1.41(1.19–1.69) and 1.32(1.09–1.59), respectively). Participants with both SCMI and high IR had the highest risk (HR 1.92; 95% CI 1.49–2.50) compared with those with neither condition. Conclusions: In adults without prior CVD, METS-IR was positively associated with SCMI. The coexistence of SCMI and high IR identified a subgroup at nearly twofold higher risk of cardiovascular mortality, supporting combined use of ECG-based injury markers and metabolic indices for cardiovascular risk stratification.

Cheon P, et al. Clin Hypertens. 2026 ;32:e33. https://doi.org/10.5646/ch.2026.32.e33

Purpose of Review: Cardiorenal syndrome refers to disorders of the heart and kidneys in which dysfunction in one organ has resulted in dysfunction of the other. Wasting continuum disorders such as cachexia are highly prevalent in cardiorenal syndrome, yet the clinical impact, pathophysiological mechanisms, and management options have not been well elucidated in previous literature. In this review, we aim to summarize current knowledge regarding the epidemiology, clinical impact, and pathophysiology of CRS-induced wasting continuum disorders, as well as highlight effective and potentially emerging treatment options. Recent Findings: Neurohormonal activation, inflammation, metabolic dysfunction, gastrointestinal abnormalities, protein degradation, and mitochondrial pathway dysfunction are pathophysiologic mechanisms underlying CRS-induced cachexia. Recent studies have investigated various treatment options targeting such mechanisms with mixed results. Summary: Early screening of wasting continuum disorders in CRS, in combination with nutritional supplementation and exercise rehabilitation strategies, is the mainstay of management. Pharmacologic optimization may also benefit patients. Future studies are necessary to improve generalizability and consensus definitions of cardio- and renal-specific wasting continuum disorders.

The aging of the global population over recent decades has resulted in an increased prevalence of hypertension in older adults. Hypertension develops with increasing age primarily due to a disastrous feedback loop of increased arterial stiffness and maladaptive hemodynamics; this is compounded by age-related changes in physiology. The risk of adverse hypertension-related outcomes concurrently increases with age, and optimal blood pressure (BP) control in older adults thus becomes increasingly important each year. The results of several randomized clinical trials (RCTs) evaluating antihypertension strategies in older adults have concluded that the potential benefits of intensive BP management outweigh the risks of harm. However, the exclusion of frail, multimorbid, and institutionalized individuals limits the generalizability of such findings to the broader population of older patients with hypertension. Secondary analyses and external studies have continued to support intensive BP control strategies in older adults with frailty or sarcopenia. Therefore, based on available evidence, clinicians should continue practicing intensive BP control strategies in the older population, yet careful consideration of functional status, life expectancy, medication side effects, polypharmacy, and multimorbidity must take place to avoid unnecessary harm. Strategies must then be tailored to accommodate modifiers such as frailty and sarcopenia in older adults with hypertension. Knowledge gaps underscore the need for future studies evaluating BP management in older adults that incorporate greater proportions of multimorbid and institutionalized individuals with frailty, assess personalization of treatment, and identify subgroups in which optimal BP levels exist or the permissibility of higher BP levels is safer than BP reduction.