Cardiovascular events
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The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population. Understanding the mechanisms that affect vascular ageing in centenarians and the underlying factors could offer valuable insights for developing strategies to improve overall healthy life span in the elderly. This review discusses these key factors influencing vascular ageing and how their modulation could foster healthy longevity.
- MeSH
- dlouhověkost * fyziologie MeSH
- kardiovaskulární nemoci patofyziologie epidemiologie MeSH
- lidé MeSH
- oxidační stres fyziologie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- stárnutí * fyziologie MeSH
- střevní mikroflóra fyziologie MeSH
- zdravé stárnutí fyziologie MeSH
- životní styl MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF) but are underused in clinical practice. Observational data suggest that hyperkalemia is the leading obstacle for the suboptimal use of MRA. OBJECTIVES: This study sought to evaluate the effects of sodium zirconium cyclosilicate (SZC) in optimizing use of spironolactone among participants with HFrEF and hyperkalemia. METHODS: REALIZE-K (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone) was a prospective, double-blind, randomized- withdrawal trial in participants with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal guideline-directed therapy (except MRA), and prevalent or incident MRA-induced hyperkalemia. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/day); those with hyperkalemia started SZC. Participants with normokalemia (potassium: 3.5-5.0 mEq/L) on SZC and spironolactone ≥25 mg/day were randomized to continued SZC or placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/day without rescue therapy for hyperkalemia [months 1-6]). The 5 secondary endpoints were tested hierarchically. Exploratory endpoints included a composite of adjudicated cardiovascular death or worsening heart failure (HF) events (hospitalizations and urgent visits). RESULTS: Overall, 203 participants were randomized (SZC: 102; placebo: 101). Higher percentage of SZC- vs placebo-treated participants had optimal response (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001). SZC (vs placebo) improved the first 4 secondary endpoints: normokalemia on randomization dose of spironolactone and without rescue therapy (58% vs 23%; OR: 4.58; 95% CI: 2.78-7.55; P < 0.001); receiving spironolactone ≥25 mg/day (81% vs 50%; OR: 4.33; 95% CI: 2.50-7.52; P < 0.001); time to hyperkalemia (HR: 0.51; 95% CI: 0.37-0.71; P < 0.001); and time to decrease/discontinuation of spironolactone due to hyperkalemia (HR: 0.37; 95% CI: 0.17-0.73; P = 0.006). There was no between-group difference in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at 6 months (-1.01 points; 95% CI: -6.64 to 4.63; P = 0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were balanced between SZC and placebo, respectively. Composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal P = 0.034). CONCLUSIONS: In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalemia and down-titration/discontinuation of spironolactone. Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone; NCT04676646).
- MeSH
- antagonisté mineralokortikoidních receptorů * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- hyperkalemie * farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- silikáty * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- spironolakton * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- srdeční selhání * farmakoterapie MeSH
- tepový objem účinky léků fyziologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS: A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS: Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).
- MeSH
- C-reaktivní protein * analýza MeSH
- cévní mozková příhoda prevence a kontrola MeSH
- dvojitá slepá metoda MeSH
- infarkt myokardu * prevence a kontrola mortalita MeSH
- Kaplanův-Meierův odhad MeSH
- kolchicin * terapeutické užití škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- recidiva MeSH
- sekundární prevence MeSH
- senioři MeSH
- spironolakton terapeutické užití škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. RESULTS: We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. CONCLUSIONS: Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).
- MeSH
- antagonisté mineralokortikoidních receptorů * terapeutické užití škodlivé účinky MeSH
- cévní mozková příhoda mortalita MeSH
- dvojitá slepá metoda MeSH
- infarkt myokardu * mortalita farmakoterapie MeSH
- Kaplanův-Meierův odhad MeSH
- kardiovaskulární nemoci mortalita prevence a kontrola MeSH
- koronární angioplastika MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- spironolakton * terapeutické užití škodlivé účinky MeSH
- srdeční selhání * farmakoterapie mortalita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
The aim of the present study was to assess systemic circulatory and tissue activities of both the classical arm and of the alternative arm of the renin-angiotensin system (RAS) in a new transgenic rat line (TG7371) that expresses angiotensin-(1-7) (ANG 1-7)-producing fusion protein; the results were compared with the activities measured in control transgene-negative Hannover Sprague-Dawley (HanSD) rats. Plasma and tissue concentrations of angiotensin II (ANG II) and ANG 1-7, and kidney mRNA expressions of receptors responsible for biological actions of ANG II and ANG 1-7 [i.e. ANG II type 1 and type 2 (AT1 and AT2) and Mas receptors] were assessed in TG7371 transgene-positive and in HanSD rats. We found that male TG7371 transgene-positive rats exhibited significantly elevated plasma, kidney, heart and lung ANG 1-7 concentrations as compared with control male HanSD rats; by contrast, there was no significant difference in ANG II concentrations and no significant differences in mRNA expression of AT1, AT2 and Mas receptors. In addition, we found that in male TG7371 transgene-positive rats blood pressure was lower than in male HanSD rats. These data indicate that the balance between the classical arm and the alternative arm of the RAS was in male TGR7371 transgene-positive rats markedly shifted in favor of the latter. In conclusion, TG7371 transgene-positive rats represent a new powerful tool to study the long-term role of the alternative arm of the RAS in the pathophysiology and potentially in the treatment of cardio-renal diseases.
- MeSH
- angiotensin I * metabolismus MeSH
- angiotensin II * MeSH
- kardiovaskulární nemoci metabolismus genetika MeSH
- krevní tlak fyziologie MeSH
- krysa rodu rattus MeSH
- ledviny metabolismus MeSH
- nemoci ledvin metabolismus genetika MeSH
- peptidové fragmenty * metabolismus MeSH
- potkani Sprague-Dawley * MeSH
- potkani transgenní * MeSH
- protoonkogen Mas MeSH
- receptor angiotensinu typ 1 genetika metabolismus MeSH
- receptory spřažené s G-proteiny genetika metabolismus MeSH
- rekombinantní fúzní proteiny metabolismus MeSH
- renin-angiotensin systém * fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT). METHODS: We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development. RESULTS: Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0-62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59-17.72, p = 0.006) and Kaplan-Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44-22.92, p = 0.013 and OR 7.29; 95% CI 1.46-36.41, p = 0.015, respectively). CONCLUSIONS: Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.
- MeSH
- diabetes mellitus * epidemiologie etiologie MeSH
- dospělí MeSH
- kardiovaskulární nemoci * epidemiologie etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- transplantace jater * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Despite secondary prevention with aspirin, patients with stable cardiovascular disease (CVD) remain at elevated long-term risk of major adverse cardiovascular events. The Cardiovascular Outcomes in People Using Anticoagulant Strategies (COMPASS) double-blind, randomized clinical trial demonstrated that aspirin plus low-dose rivaroxaban (COMPASS regime) significantly decreased the incidence of major adverse cardiovascular events by 24% compared with aspirin alone. However, the mechanisms underlying these potential synergistic/nonantithrombotic effects remain elusive. Extracellular vesicles (EVs) are crucial messengers regulating a myriad of biological/pathological processes and are highly implicated in CVD. OBJECTIVES: We hypothesized that circulating EV profiles reflect the cardioprotective properties of the COMPASS regime. METHODS: A cohort of stable CVD patients (N = 40) who participated in the COMPASS trial and were previously randomized to receive aspirin were prospectively recruited and assigned a revised regimen of open-label aspirin plus rivaroxaban. Blood samples were obtained at baseline (aspirin only) and 6-month follow-up. Plasma EV concentration, size, and origin were analyzed by nanoparticle tracking analysis and flow cytometry. EVs were enriched by ultracentrifugation for proteomic analysis. RESULTS: The COMPASS regime fundamentally altered small (<200 nm) and large (200-1000 nm) EV concentration and size compared with aspirin alone. Crucially, levels of platelet-derived and myeloperoxidase-positive EVs became significantly decreased at follow-up. Comparative proteomic characterization further revealed a significant decrease in highly proinflammatory protein expression at follow-up. CONCLUSION: The observed changes in EV subpopulations, together with the differential protein expression profiles, suggest amelioration of an underlying proinflammatory and prothrombotic state upon dual therapy, which may be of clinical relevance toward understanding the fundamental mechanism underlying the reported superior cardiovascular outcomes associated with this antithrombotic regimen.
- MeSH
- Aspirin * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- extracelulární vezikuly * metabolismus účinky léků MeSH
- inhibitory agregace trombocytů * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- inhibitory faktoru Xa * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- kardiovaskulární nemoci * krev prevence a kontrola farmakoterapie MeSH
- kombinovaná farmakoterapie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu krev MeSH
- prospektivní studie MeSH
- proteomika metody MeSH
- rivaroxaban * aplikace a dávkování MeSH
- senioři MeSH
- trombóza krev prevence a kontrola farmakoterapie MeSH
- výsledek terapie MeSH
- zánět krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: To predict worsening heart failure hospitalizations (WHFHs), the HeartInsight multiparametric algorithm calculates a heart failure (HF) Score based on temporal trends of physiologic parameters obtained through automatic daily remote monitoring of implantable cardioverter-defibrillators (ICDs). OBJECTIVE: We studied the association of the baseline HF Score, determined at algorithm activation, with long-term patient outcomes. METHODS: Data from 9 clinical trials were pooled, including 1841 ICD patients with a preimplantation ejection fraction ≤35%, New York Heart Association class II/III, and no long-standing atrial fibrillation. The primary end point was a composite of death or WHFH. RESULTS: After a median follow-up of 631 days (interquartile range, 385-865 days), there were 243 WHFHs in 173 patients (9.4%) and 122 deaths (6.6%), 52 of which (42.6%) were cardiovascular. The primary end point occurred in 265 patients (14.4%). A multivariable time-to-first-event analysis showed that a high baseline HF Score (>23, as determined by a time-dependent receiver operating characteristics curve analysis) was significantly associated with the occurrence of the primary end point (adjusted hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.54-2.71; P < .0001), all-cause death (HR, 2.37; CI, 1.56-3.58; P < .0001), cardiovascular death (HR, 2.19; CI, 1.14-4.22; P = .019), and WHFH (HR, 1.91; CI, 1.35-2.71; P = .0003). In a hierarchical event analysis of all-cause death as the outcome with highest priority and WHFHs as repeated event outcomes, the win ratio was 2.47 (CI, 1.89-3.24; P < .0001). CONCLUSION: Based on a retrospective analysis of clinical trial data with adjudicated events, baseline HF Score derived from device-monitored variables was able to stratify patients at higher long-term risk of death or WHFH.
- MeSH
- algoritmy MeSH
- časové faktory MeSH
- defibrilátory implantabilní * MeSH
- klinické zkoušky jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- senioři MeSH
- srdeční selhání * terapie patofyziologie mortalita MeSH
- technologie dálkového snímání metody MeSH
- tepový objem fyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry-Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.
- MeSH
- kůže krevní zásobení MeSH
- lidé MeSH
- mikrocévy diagnostické zobrazování MeSH
- optoakustické techniky * metody přístrojové vybavení MeSH
- revmatoidní artritida diagnostické zobrazování MeSH
- zobrazování trojrozměrné * metody přístrojové vybavení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Androgen-receptor pathway inhibitors (ARPIs) have dramatically changed the management of advanced/metastatic prostate cancer (PCa). However, their cardiovascular toxicity remains to be clarified. OBJECTIVE: To analyze and compare the risks of cardiovascular events secondary to treatment of PCa patients with different ARPIs. METHODS: In August 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled studies (RCTs) that analyze PCa patients treated with abiraterone, apalutamide, darolutamide, and enzalutamide. The primary outcomes of interest were the incidence of cardiac disorder, heart failure, ischemic heart disease (IHD), atrial fibrillation (AF), and hypertension. Network meta-analyses (NMAs) were conducted to compare the differential outcomes of each ARPI plus androgen deprivation therapy (ADT) compared to standard of care (SOC). RESULTS: Overall, 26 RCTs were included. ARPIs were associated with an increased risk of cardiac disorders (RR: 1.74, 95% CI: 1.13-2.68, p = 0.01), heart failure (RR: 2.49, 95% CI: 1.05-5.91, p = 0.04), AF (RR: 2.15, 95% CI: 1.14-4.07, p = 0.02), and hypertension (RR: 2.06, 95% CI: 1.67-2.54, p < 0.01) at grade ≥3. Based on NMAs, abiraterone increased the risk of grade ≥3 cardiac disorder (RR:2.40, 95% CI: 1.42-4.06) and hypertension (RR:2.19, 95% CI: 1.77-2.70). Enzalutamide was associated with the increase of grade ≥3 AF(RR: 3.17, 95% CI: 1.05-9.58) and hypertension (RR:2.30, 95% CI: 1.82-2.92). CONCLUSIONS: The addition of ARPIs to ADT increases the risk of cardiac disorders, including IHD and AF, as well as hypertension. Each ARPI exhibits a distinct cardiovascular event profile. Selecting patients carefully and vigilant monitoring for cardiovascular issues is imperative for those undergoing ARPI + ADT treatment.
- MeSH
- androsteny MeSH
- antagonisté androgenních receptorů * škodlivé účinky terapeutické užití MeSH
- benzamidy škodlivé účinky MeSH
- fenylthiohydantoin MeSH
- kardiovaskulární nemoci * chemicky indukované epidemiologie MeSH
- lidé MeSH
- nádory prostaty * farmakoterapie patologie MeSH
- nitrily škodlivé účinky MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- síťová metaanalýza MeSH
- systematický přehled MeSH