卢永康
中国医学科学院阜外医院深圳医院 重症医学科
Introduction:The aim of the current study was to evaluate the association of spironolactone and arterial stiffness and composite cardiovascular disease (CVD, including coronary heart disease, congestive heart failure and ischemic stroke) in hypertensive patients.Material and methods:Baseline data were collected and arterial stiffness was presented by carotid-femoral pulse wave velocity (cf-PWV) using applanation tonometry. Serum levels of fasting plasma glucose, total cholesterol, C-reactive protein and creatinine were measured using an automatic biochemistry analyzer. Plasma aldosterone concentration and plasma renin activity were determined by radioimmunoassay. The associations of spironolactone and arterial stiffness and composite CVD were evaluated.Results:Compared to patients without spironolactone (n = 274), those with spironolactone (n = 170) were older and more likely to have diabetes and chronic heart failure. No differences in antihypertensive medications used were observed except for spironolactone. Mean number of antihypertensive medications used was significantly higher in the spironolactone group (2.6 ±0.8 vs. 2.2 ±0.6). Compared to patients without spironolactone, those with spironolactone had significantly lower cf-PWV (9.4 ±1.8 vs. 10.1 ±2.2 m/s). After adjustment for covariates, spironolactone was still associated with 10% lower risk of arterial stiffness, with a 95% confidence interval (CI) of 0.85-0.97. In patients without arterial stiffness, after adjustment for covariates, no significant association of spironolactone and composite CVD was observed. However, in patients with increased arterial stiffness, after adjustment for covariates, spironolactone was still independently associated with 11% lower risk of composite CVD (95% CI: 0.83-0.97).Conclusions:Spironolactone treatment is independently associated with lower cf-PWV and lower prevalence of composite CVD in patients with increased arterial stiffness.
Archives of medical science : AMS 2022
Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 µM; interquartile range [IQR]: 0.43-0.78 versus 0.42 µM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.
Reviews in cardiovascular medicine 2021
Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.
Experimental cell research 2021
BACKGROUND:Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients.MATERIAL AND METHODS:A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.
Medicine 2020
INTRODUCTION:The current study aimed to evaluate the association of anti-hyperuricemia treatment and prevalent cardiovascular disease (CVD) in hypertensive patients.MATERIAL AND METHODS:Primary hypertensive patients with hyperuricemia were enrolled. All participants were separated into two groups: anti-hyperuricemia and control groups (without anti-hyperuricemia treatment). Comparisons of prevalent CVD including coronary heart disease, ischemic stroke and heart failure were made and the associations of anti-hyperuricemia treatment and prevalent CVD were analyzed.RESULTS:Compared to the anti-hyperuricemia group, patients in the control group had significantly higher serum C-reactive protein (10.6 ±2.8 vs. 7.4 ±1.2 mg/dl) and uric acid (UA) levels (438 ±33 vs. 379 ±64 µmol/l), and were more likely to receive β-blockers (34.2% vs. 31.1%) and calcium channel blockers (49.2% vs. 43.4%). The prevalence of ischemic stroke was higher in the control group (15.8% vs. 11.3%). Compared to other groups, blood pressure was significantly higher in patients in the 4th quartile serum UA level group. In the unadjusted model, anti-hyperuricemia treatment was significantly associated with a reduced odds ratio (OR) of composite CVD. After adjusting for potential covariates, OR of anti-hyperuricemia treatment for composite CVD was 0.89 with a 95% confidence interval (IC) of 0.82-0.98. Associations of anti-hyperuricemia treatment and ischemic stroke were also significant with OR = 0.93 and 95% CI: 0.88-0.99, while associations of anti-hyperuricemia with coronary heart disease and heart failure attenuated into insignificance after adjusting for covariates.CONCLUSIONS:In hypertensive patients with hyperuricemia, anti-hyperuricemia treatment was associated with lower odds of prevalent CVD.
Archives of medical science : AMS 2020
