Longevity is a relevant cardiovascular (CV) endpoint because survival integrates incident CV disease (CVD), competing non-CVD risks, and the physiological reserve that determines resilience to aging and chronic illness. Two related constructs, physical activity (PA; a modifiable behavior) and cardiorespiratory fitness (CRF; an integrative phenotype reflecting habitual PA, genetics, cardiopulmonary function, skeletal muscle oxidative capacity, and comorbidity), are consistently associated with lower all-cause and CVD mortality across diverse populations. In this invited narrative review, we synthesize evidence linking PA and CRF to longevity, highlight the dose-response nature of benefits and the importance of activity domain and intensity, and explain why CRF generally outperforms self-reported PA for risk prediction. We address challenges in causal inference, residual confounding variables, reverse causation, and selection/measurement bias, and emphasize approaches that strengthen inference, including device-based PA assessment (e.g., accelerometry), repeated measures, and triangulation with mechanistic and trial evidence. Mechanistic pathways plausibly linking PA and CRF to survival include favorable effects on blood pressure, glycemia and insulin sensitivity, adiposity and body composition, vascular reactivity, autonomic balance, inflammation and immune function, thrombosis, and preservation of skeletal muscle and mitochondrial reserve. We review evidence in particularly relevant subgroups and discuss the "extreme exercise hypothesis", distinguishing mortality from risks, such as atrial fibrillation and accelerated coronary calcification, in endurance athletes. We conclude with practical actions for clinicians and health systems, such as prescribing activities based on the frequency, intensity, time, and type (FITT) principles, incorporating resistance training, treating CRF as a vital sign, and addressing common implementation barriers.

The landscape of lipid management has transitioned from a statin-monotherapy and statin-intensification paradigm to a sophisticated, multi-axis intervention model targeting low-density lipoprotein cholesterol, triglyceride-rich lipoproteins, lipoprotein(a), and vascular inflammation. The emergence of PCSK9-targeted small interfering RNA therapies, CETP inhibitors, and Lp(a)-directed antisense and RNA based agents has enabled complementary modulation of diverse lipid pathways through distinct molecular targets. However, this increasingly multidrug approach may also increase treatment complexity, healthcare burden, and adherence challenges, particularly among high-risk patients already receiving multidrug cardiometabolic therapy. Although intensive and sustained LDL-C lowering remains foundational to preventive cardiology, the real-world effectiveness of increasingly complex treatment strategies may ultimately depend on long-term adherence, affordability, patient capacity, and implementation feasibility. We propose a Clinical Prioritization and Personalization Framework centered on individualized risk-based intensification, comprehensive residual risk management, and optimization of treatment delivery to achieve sustainable, patient-centered cardiovascular protection.

Coronary artery ectatic/aneurysmatic disease (CAE/CAA) is a rare but clinically significant condition characterized by abnormal dilatation of the coronary arteries, either diffusely (CAE) or focally (CAA). Its pathophysiology is multifactorial, involving atherosclerosis, genetic predisposition, systemic autoimmunity, and infectious triggers, with distinct etiologies in adults (e.g., atherosclerosis, connective tissue disorders) and children (e.g., Kawasaki disease, multisystem inflammatory syndrome in children). CAE/CAA is associated with increased risks of thrombosis, embolization, and acute coronary syndromes, even in the absence of obstructive coronary artery disease. Diagnostic evaluation relies on multimodality imaging, including transthoracic echocardiography (especially in children), computed tomography coronary angiography, cardiovascular magnetic resonance angiography, and invasive coronary angiography with intravascular ultrasound. Each modality offers unique advantages, but challenges such as radiation exposure, contrast use, expertise and availability persist. Therapeutic management remains empirical due to a lack of randomized trials. In adults, risk factor modification, statins, angiotensin converting enzyme inhibitors / angiotensin receptor blockers, calcium channel blockers are commonly used. Optimal strategies for antiplatelet/anticoagulant treatment are currently under debate. In children, anticoagulation and antiplatelet therapy are recommended for large aneurysms, particularly in Kawasaki disease. Future research should focus on elucidating pathophysiology, comparing imaging modalities, and establishing evidence-based treatment strategies to improve outcomes in this complex patient population.