Clonal hematopoiesis of indeterminate potential (CHIP) raises cardiovascular risk, yet the size of a clone in blood does not by itself explain how that clone contributes to disease. We argue that selection acts not once but at three dissociable checkpoints: competition among hematopoietic stem cells, myeloid lineage output, and entry, niche occupancy and local proliferation in tissue. Blood variant allele frequency (VAF), the measurement on which the clinical literature rests, is the product of the first two and therefore does not report the mutant fraction among stem cells; because lineage bias is gene-dependent, VAF-matched comparisons across drivers are not equivalent. Evidence from TET2, DNMT3A, ASXL1, JAK2 and Trp53 models shows that an advantage at one checkpoint need not carry to the next, and that the checkpoints separate gene by gene. At checkpoint 1, cardiovascular risk factors and tissue injury act on stem cells both directly and by remodeling the bone marrow niche, but whether cardiovascular stress selects mutant clones specifically through defined niche changes remains unresolved. At checkpoint 3, human cross-sectional data have not demonstrated preferential recruitment of mutant macrophages into cardiovascular tissue and cannot separate recruitment from retention, niche occupancy or local proliferation, and irradiated transplantation chimeras measure how a clone fills a vacated niche rather than how it competes for an occupied one. Existing pharmacology — canakinumab, colchicine, metformin — is read out at checkpoints 1 and 2 alone. Genotype-resolved, spatial and longitudinal measurements are needed to make the framework testable.
Ischemic heart disease is one of the major diseases that affect human health, and it has high morbidity and mortality rates globally. The primary clinical strategy for its treatment is prompt restoration of blood supply to the ischemic myocardium. Nevertheless, reperfusion of blood flow can exacerbate myocardial damage, leading to myocardial ischemia/reperfusion injury (MIRI). RhoA/rho-associated protein kinase (ROCK) signaling plays a pivotal role in cardiovascular diseases and is a candidate therapeutic target in MIRI. However, its role is bidirectional: the intensity and duration of activation, the phase of ischemia and reperfusion, the cell type in which the signal arises, and the downstream effector engaged together determine whether RhoA signaling injures or protects the myocardium. Protection is carried by branches acting through protein kinase D, PINK1/Parkin, and myocardin-related transcription factor A so that intervention is directed at correcting pathological overactivation rather than blocking the pathway. Traditional Chinese medicine (TCM) has long been used in ischemic heart disease and is extensively studied as an intervention against MIRI. In addition, active ingredients of Chinese medicinal herbs, TCM compound prescriptions, and electroacupuncture alleviate oxidative stress, maintain calcium ion homeostasis and mitochondrial function, and suppress inflammatory responses and apoptosis, and these effects are accompanied by suppression of excessive RhoA/ROCK activation. However, most of the available studies report only changes in RhoA or ROCK expression, and the evidence establishing RhoA as a necessary target of these interventions remains limited. The clinical trials completed for these interventions used coronary flow and exercise capacity as endpoints without measuring the pathway in patients, and their translation remains to be established. This narrative review summarizes the research on TCM modulation of the RhoA signaling pathway in MIRI and appraises the current state of its clinical translation.
The aging population in China continues to intensify, and ischemic heart disease (IHD) has become the leading cause of death and disability among the elderly population (> 60 years), with a substantial disease burden. This review is based on multiple databases and summarizes the epidemiological characteristics, multidimensional risk factors, pathogenesis, diagnosis and treatment techniques, as well as prevention and control progress of elderly IHD in China. Although the standardized incidence and mortality indicators of IHD among the elderly in China have slightly declined, driven by population aging, the absolute total number of cases, deaths, and Disability-Adjusted Life-Years (DALYs) continues to rise. The disease burden shows a distribution pattern of high in the north and low in the south, higher in rural areas than in cities, concentrated in the population over 70 years old, and accelerated risk growth among elderly women; Non-modifiable factors (age, gender, heredity), unhealthy lifestyle, hypertension/diabetes and other comorbidity, psychosocial factors, and environmental pollution constitute a superposition risk. Aging related coronary microvascular disease, mitochondrial dysfunction, chronic low-grade inflammation, and imbalance of multiple signaling pathways are the core pathological mechanisms of elderly ischemic myocardial injury. Non invasive cardiac imaging, high-sensitivity troponin, and multiple-omics biomarkers may be can improve diagnostic accuracy in elderly patients with atypical symptoms. A hierarchical chronic disease prevention and control system has been established in China, but weak community-level monitoring, insufficient disease awareness among the population, and the slow translation of research findings into clinical practice remain weaknesses. In the future, it is necessary to rely on local cohorts to deepen research on the etiology and mechanism of aging, promote comprehensive multidimensional risk-factor intervention, and provide scientific basis for reducing the burden of cardiovascular disease in the elderly and achieving healthy aging.
BackgroundAtmospheric pressure affects the boiling point of water and may influence thermal lesion formation during radiofrequency (RF) ablation. However, whether atmospheric pressure alters RF lesion formation and steam-pop risk under fixed ablation index (AI) targets remains unknown.MethodsA total of 360 analyzable lesions were created in 36 ex vivo porcine hearts using the same RF ablation system, which was transported and used consistently at three sites with different atmospheric pressures: Beijing (1,014 hPa), Xining (770 hPa), and Lhasa (650 hPa). At each site, 30 analyzable lesions were obtained at each target AI value (300, 400, 500, and 600). Lesion dimensions, impedance reduction, ablation duration, temperature, and steam-pop occurrence were recorded. Differences among sites were assessed using analysis of variance and Fisher's exact test. A multiple linear regression model was constructed to evaluate the relationship between atmospheric pressure, AI, and lesion volume.ResultsAt fixed AI targets, lesions created at lower-pressure sites were significantly shallower and had smaller volumes (all P < 0.05), whereas surface and maximum diameters remained similar among the three sites. Steam pops occurred in 0/120 (0.0%) RF applications in Beijing, 2/122 (1.6%) in Xining, and 6/126 (4.8%) in Lhasa (overall P = 0.031). Impedance reductions differed significantly among sites at 3 and 10 s (both P < 0.001), but not at 5 s (P = 0.498). Atmospheric pressure and AI jointly explained 88.4% of the variation in lesion volume (R2 = 0.884), enabling derivation of a hypothesis-generating AI correction equation.ConclusionWithin the natural range of atmospheric pressures examined, lower atmospheric pressure was associated with shallower and smaller-volume RF lesions at fixed AI targets and a higher observed incidence of steam pops. These findings suggest that atmospheric pressure may influence RF lesion formation and steam-pop occurrence, warranting further mechanistic and in vivo validation.
BackgroundHypertensive disorders of pregnancy (HDP) are associated with increased long-term cardiovascular, cerebrovascular, and renal risk, yet pathways linking HDP to later organ damage remain poorly understood. Persistent vascular dysfunction after HDP and subsequent cardiovascular risk factors may contribute to long-term hypertension-mediated organ damage (HMOD). We evaluated associations between HDP and long-term cerebral, cardiac, vascular, and renal HMOD across clinically relevant risk subgroups.MethodsIn this UK Biobank matched cohort study, parous females with a history of HDP were matched 1:4 to females without HDP by age at first delivery and parity. HMOD was assessed using white matter hyperintensity volume, left ventricular ejection fraction, pulse wave arterial stiffness index, and urine albumin-to-creatinine ratio. Multivariate linear regression models adjusted for cardiovascular risk factors assessed associations between HDP and each HMOD marker. Analyses were stratified by subsequent hypertension, menopausal status, age ≥50 years, antihypertensive medication use, and time since HDP ≥10 years.ResultsAmong participants (mean age 50 ± 7 years), HDP was not associated with white matter hyperintensity volume (β = −0.31, 95% CI −1.04 to 0.41, p = 0.401), left ventricular ejection fraction (β = 0.76, 95% CI −0.38 to 1.90, p = 0.193), pulse wave arterial stiffness index (β = 0.14, 95% CI −0.36 to 0.64, p = 0.595), or urine albumin-to-creatinine ratio (β = −0.12, 95% CI −0.51 to 0.26, p = 0.535) after multivariate adjustment. Subgroup analyses revealed an isolated significant adjusted association with lower log-transformed white matter hyperintensity volume among participants with subsequent hypertension (β = −0.41, 95% CI −0.79 to −0.03, p = 0.033), while other associations were not consistently significant.DiscussionHDP was not consistently associated with selected measures of long-term subclinical HMOD across clinically relevant subgroups. Established long-term cardiovascular and renal risks following HDP may not be uniformly reflected by HMOD markers assessed at a single time point later in life. Future longitudinal studies using repeated assessments are needed to identify which HMOD phenotypes emerge following HDP and whether they predict or mediate subsequent cardiovascular, cerebrovascular, and renal outcomes.
