Qingchun Zeng

Introduction: Lipoprotein(a) [Lp(a)] is a genetically determined cardiovascular risk factor that is largely unaffected by statins. Although PCSK9 inhibitors can lower Lp(a), comparative evidence among agents is limited. Methods: We conducted a systematic review and frequentist random−effects network meta−analysis of randomized controlled trials from database inception to February 2026 (PROSPERO: CRD420251208404). The primary outcome was the percentage change in Lp(a) from baseline. Secondary outcomes included changes in low−density lipoprotein cholesterol (LDL − C), non−high−density lipoprotein cholesterol (non − HDL−C), triglyceride (TG), total cholesterol (TC), high−density lipoprotein cholesterol (HDL − C), and apolipoprotein B (ApoB). Safety outcomes were adverse events (AEs) and serious adverse events (SAEs). Certainty of evidence was assessed using CINeMA. Sensitivity analyses were conducted according to the reported Lp(a) unit and by restricting the analysis to label−approved dose regimens. Results: Sixty − two trials involving 73,240 participants and six PCSK9 inhibitors were included. All evaluated agents were associated with reductions in Lp(a) versus placebo. The largest point estimates were observed for ongericimab (MD = − 46.36%, 95% CI − 55.96 to − 36.77) and tafolecimab (MD = − 41.12%, 95% CI − 50.73 to − 31.51), although certainty was low and comparisons were predominantly indirect. Sensitivity analyses yielded broadly similar results. No statistically significant differences in overall AEs or SAEs were detected versus placebo. Conclusions: PCSK9 inhibitors may reduce Lp(a) and improve atherogenic lipid profiles. Comparative effects among individual agents remain uncertain because the evidence was mainly indirect and of low certainty. Whether Lp(a) lowering itself improves cardiovascular outcomes remains unknown.

Objective: This retrospective study compared the effects of indobufen versus aspirin, each combined with clopidogrel, on serum uric acid (SUA) levels and gout attacks in patients undergoing coronary stenting. Methods: Among 213 enrolled patients, 156 were included after propensity score matching and assigned to either the indobufen plus clopidogrel group ( n = 78) or the aspirin plus clopidogrel group ( n = 78). SUA levels were measured at baseline and at the 1-month, 6-month, and 1-year follow-ups. Gout attacks and major cardiovascular events were recorded throughout the study. Results: Baseline characteristics were comparable. The indobufen group showed significant reductions in SUA levels at all follow-ups (all, P < 0.001), whereas levels in the aspirin group remained stable. Although the initial gout attack rates at baseline were similar between groups, the probability of recurrence during follow-up was lower in the indobufen group. Cardiovascular safety profiles were comparable between groups. Conclusion: Indobufen plus clopidogrel significantly reduced SUA levels and showed a favorable trend in reducing gout recurrences without compromising cardiovascular safety.

BACKGROUND: Circular RNAs are implicated in various physiopathologic activities and play a crucial role in calcific aortic valve disease (CAVD) progression. However, the role of coding circular RNAs in CAVD remains unclear. In this study, we aimed to characterize coding circular RNAs and explore their functions in CAVD. METHODS: Using a systematic approach from transcriptome sequencing to experimental validation, we identified circZBTB44, confirmed its translation into ZBTB44-342aa, and investigated the function and mechanism of this peptide in CAVD using both cellular and animal models. RESULTS: We found that circZBTB44 promotes the translation of ZBTB44-342aa through N6-methyladenosine modifications. Functionally, ZBTB44-342aa binds to IGF2BP3 (insulin-like growth factor 2 mRNA-binding protein 3), which inhibits mitochondrial damage and mtDNA release into the cytoplasm, thereby suppressing the activation of the cGAS-STING (stimulator of interferon genes) pathway and alleviating the osteogenic differentiation of human aortic valve interstitial cells. Consistent with this, both circZBTB44 overexpression and STING deprivation alleviated aortic valve lesions in vivo, while in vitro, overexpressing circZBTB44 or adding ZBTB44-342aa recombinant protein inhibited the osteogenic response. Conversely, siRNA-mediated knockdown of circZBTB44 enhanced this response. Furthermore, STING inhibition by H-151 alleviated the osteogenic response, whereas its activation by dimeric amidobenzimidazole exacerbated it. CONCLUSIONS: This study demonstrates that circZBTB44-encoded ZBTB44-342aa alleviates CAVD progression by inhibiting the cGAS-STING signaling pathway, thereby identifying both circZBTB44 and STING as potential therapeutic targets.

During fibrogenesis, certain negative feedback loops are elicited to restrain persistent and hyperactive fibrotic responses. Activated fibroblasts have been found to acquire anti‐fibrotic phenotypes. However, the specific inhibitory modulators remain largely enigmatic. Thus, the present study aimed to examine the intrinsic autoregulatory mechanisms of fibroblasts. Here, we demonstrated that angiotensin II (AngII)‐primed cardiac myofibroblast moderated subsequent profibrotic activation. More importantly, this suppressive action was dependent on small extracellular vesicles (sEVs). Strikingly, small RNA sequencing identified an abundant presence of Piwi‐interacting RNAs (piRNAs) in sEVs. In cultured primary cardiac fibroblasts, piRNA‐62788 was induced by AngII receptor type 2 (AT ₂ R) stimulation and encapsulated into sEVs. Furthermore, fibrogenic responses were attenuated by piRNA‐62788 overexpression, whereas aggravated by piRNA‐62788 knockdown. In a mouse model of transverse aortic constriction, either piRNA‐62788 agomir or circulating sEVs of patients with heart failure (HF) mitigated adverse cardiac remodelling, while piRNA‐62788 inhibitor‐containing sEVs accentuated myocardial fibrosis. Mechanistically, piRNA‐62788 formed a functional complex with PIWI‐like protein 2 (PIWIL2) and bound to the 3’ untranslated region (UTR) region of serum response factor ( Srf ) mRNA transcripts, leading to inhibition of the SRF signalling. Additionally, plasma sEV‐derived piRNA‐62788 was significantly upregulated in HF patients and negatively correlated with left ventricular ejection fraction. Collectively, we uncovered a protective negative feedback circuit controlled by AngII/AT ₂ R/sEVs axis. Understanding this endogenous anti‐fibrotic pathway may hold therapeutic promise in HF.

Objective: The C-reactive protein-triglyceride-glucose index (CTI) is a novel biomarker that integrates measures of insulin resistance and inflammation. Its association with cardiovascular disease (CVD) risk across various glycemic statuses remains unclear. Methods: This prospective study included 7,584 middle-aged and elderly participants from the China Health and Retirement Longitudinal Study (CHARLS). CTI was calculated using the formula 0.412*Ln(CRP) + Ln(TG × FPG)/2. Cox proportional hazards models and restricted cubic splines were employed to evaluate the relationship between CTI and CVD risk, with subgroup analyses conducted based on gender, age, and glycemic status.. Results: Over a median follow-up period of 108.1 months, 1,989 participants (26.23%) developed CVD. The incidence of CVD increased significantly across ascending CTI quartiles (Q1: 20.78% to Q4: 31.65%). A positive linear association was observed that remained consistent across both genders and age groups. Higher CTI quartiles (Q3/Q4) were associated with a significantly elevated risk of CVD, particularly among males (hazard ratio [HR] up to 1.58) and middle-aged individuals (HR 1.57). Notably, an elevated CTI was linked to an increased risk of CVD in participants with normal glucose regulation but not in those classified as prediabetic or diabetic. Conclusions: The CTI serves as an independent predictor of CVD risk within the general middle-aged and elderly population. This association is most pronounced in individuals exhibiting normal glucose regulation, underscoring the potential utility of CTI for early risk stratification as well as the necessity for tailored prevention strategies informed by glycemic status.

Background: The long‐term effects of physical activity (PA) variability and cumulative PA (CPA) from young adulthood on cardiac remodeling remain controversial, and it is unclear whether these effects resemble those observed in elite athletes. Methods: A total of 1465 participants with recorded PA spanning a 30‐year period were included in this study. PA levels were assessed at 9 follow‐up visits using the CARDIA (Coronary Artery Risk Development in Young Adults) questionnaire. At year 30, left ventricular structure and function were evaluated using standardized echocardiography. CPA was calculated as the sum of average PA levels between consecutive visits multiplied by the corresponding intervisit intervals (in years). PA variability was quantified using average real variability (ARVPA). Additionally, participants were categorized into 4 groups: sustained low CPA and ARVPA group, low CPA and high ARVPA group, high CPA and low ARVPA group, and high CPA and high ARVPA group. Results: This study included 849 women (57.1%), 883 White participants (60.3%), and had a mean age of 55.3 years. Participants in the sustained high CPA group exhibited lower incidence of hypertension and diabetes. Multiple linear regression analyses showed that, compared with the sustained‐low‐CPA group, the sustained‐high‐CPA group and high‐CPA and high‐ARVPA group exhibited increased left ventricular end‐diastolic dimension index, and the high‐CPA and high‐ARVPA group revealed an increased left ventricular mass index and left atrial volume index. Conclusions: Our study suggests that high CPA, even when accompanied with high variability in PA levels, is associated with alterations in left ventricular structure in midlife.

Aims: The study aimed to evaluate longitudinal adiposity exposure, assessed by body roundness index (BRI), from young adulthood and its association with the risk of coronary artery calcification (CAC) incidence in mid-life. Methods and results: We included 2102 participants from the CARDIA study with available BRI measurements at eight follow-up visits over 25 years. Cardiac computed tomography at the year 25 exam was used to assess the presence of CAC (CAC > 0). The cumulative BRI (cBRI) was calculated as the mean of the BRI between consecutive visits multiplied by the number of years. Logistic regression models and restricted cubic spline (RCS) analyses were used to assess the relationship between cBRI and the risk of CAC incidence. A total of 598 participants developed CAC over the 25-year follow-up period. Higher cBRI was associated with an increased risk of CAC incidence. Participants were divided into four quartiles based on cBRI. In model 3, the odds ratio (OR) for CAC was 2.52(95%CI, 1.82–3.49) in the top quartile of cBRI. RCS analyses suggested a linear relationship between cBRI and the risk of CAC incidence. Furthermore, multivariable Cox regression showed that individuals in the higher cBRI had a higher risk of all-cause mortality (1.009; 95% CI, 1.003–1.016). Conclusion: Greater cBRI from early adulthood was associated with an elevated risk of CAC incidence in mid-life. These findings uncover potential evidence to support that BRI may be a useful marker for identifying individuals at high risk of CAC.

The neutrophil-percentage-to-albumin ratio (NPAR) has emerged as a concise and effective biomarker for assessing systemic inflammatory status, with established prognostic value for mortality risk across various disease populations. This study aimed to elucidate the association between NPAR and both all-cause and cardiovascular mortality in patients with diabetes and prediabetes. A cohort of 8560 patients with diabetes and prediabetes was recruited from the National Health and Nutrition Examination Survey (NHANES), with mortality outcomes tracked through the National Death Index up to December 31, 2019. A weighted Cox regression model was used to evaluate the association of NPAR with all-cause and cardiovascular mortality. The restricted cubic spline (RCS) curve was used to assess the nonlinear relationship between NPAR and mortality outcomes. Subgroup analysis was conducted to evaluate the differences in the predictive performance of various NPAR features across different subgroups. Cox regression analysis indicated that participants in the highest quartile of NPAR exhibited a substantially increased risk of all-cause mortality (hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.28–1.87) and cardiovascular death (HR 2.04; 95% CI 1.47–2.84) compared to the reference group. The RCS curve further illustrated a significant nonlinear correlation between NPAR and outcomes in patients with diabetes and prediabetes. NPAR can serve as a robust nonlinear predictor for both all-cause and cardiovascular mortality in individuals diagnosed with diabetes or prediabetes.

Background: Due to inadequate healthcare facilities and certain technologies in Afghanistan, many Afghan patients seek medical treatment abroad. Thus, this study aimed to determine the factors that influence Afghan patients’ decision to seek medical treatment abroad. Methods: A cross-sectional study was conducted on 384 respondents in the center of the Special Commission, dispatching the patients to Torkham from June to September 2024 in Jalalabad City, Afghanistan. A non-probability convenience sampling method was used to select study participants. Data were collected using a pretested structured questionnaire. A hierarchical regression analysis was conducted to determine the factors influencing their satisfaction level toward medical treatment in Pakistan. Results: A total of 384 respondents were enrolled, including 64.9% male and 35.1% female. 88.10% of participants were satisfied with medical treatment in Pakistan. 49.5% of respondents obtained information about medical tourism primarily from relatives. Among them, 24.2% were cancer patients, 16% were cardiology patients, 10.1% were surgical patients, and 8.8% were kidney patients. Medicines used in Afghanistan are of low quality; Pakistan’s availability of internationally accredited hospitals, cultural/religious similarity, well-experienced and reputable doctors, similar language, and high-quality medical facilities with internationally certified physicians and staff were top-ranked items. According to regression analysis, the facility and services factor was the strongest factor (β = 0.386, t = 8.508, p = 0.001), followed by the country environment (β = 0.213, t = 4.697, p = 0.001) and medical tourism cost factor (β = 0.142, t = 3.198, p = 0.001). Conclusion: The study concluded that facility and service factors were the strongest predictors of medical tourism, followed by the country’s environment and medical tourism cost. Therefore, healthcare providers and policymakers need to consider the diverse preferences of Afghan patients and provide accurate, accessible healthcare services and advanced professional training of the healthcare providers, including attitude towards services.