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The effect of beetroot inorganic nitrate supplementation on cardiovascular risk factors: A systematic review and meta-regression of randomized controlled trials.
Bahrami, LS, Arabi, SM, Feizy, Z, Rezvani, R
Nitric oxide : biology and chemistry. 2021;:8-22
Abstract
OBJECTIVES Inorganic nitrate is one of the most effective compounds in beetroot for improving cardiovascular function due to its conversion to nitric oxide in the body. This review and meta-analysis aimed to investigate the role of beetroot inorganic nitrate supplementation on adults' cardiovascular risk factors. METHODS We conducted a systematic literature review of articles published without time limitation until November 2020 in PubMed, Embase, ISI Web of Science, Scopus, Cochrane Library, and gray literature databases. We included the original randomized clinical trials (RCTs) in which the effect of beetroot inorganic nitrate supplementation on endothelial function, arterial stiffness, and blood pressure was studied. RESULTS 43 studies were included for qualitative synthesis, out of which 27 were eligible for meta-analysis. Beetroot inorganic nitrate supplementation significantly decreased Arterial Stiffness (Pulse Wave Velocity (-0.27 m/s, p = 0.04)) and increased Endothelial function (Flow Mediated Dilation: 0.62%, p = 0.002) but did not change other parameters (p > 0.05). CONCLUSION Beetroot inorganic nitrate supplementation might have a beneficial effect on cardiovascular risk factors. Further high-quality investigations will be needed to provide sufficient evidence.
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Venoarterial extracorporeal membrane oxygenation as mechanical circulatory support in adult septic shock: a systematic review and meta-analysis with individual participant data meta-regression analysis.
Ling, RR, Ramanathan, K, Poon, WH, Tan, CS, Brechot, N, Brodie, D, Combes, A, MacLaren, G
Critical care (London, England). 2021;(1):246
Abstract
BACKGROUND While recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA ECMO, and identify factors associated with survival. METHODS We searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st June 2021, and included all relevant publications reporting on > 5 adult patients requiring VA ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted. DATA SYNTHESIS We included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI]: 23.6%-50.1%). Survival among patients with left ventricular ejection fraction (LVEF) < 20% (62.0%, 95%-CI: 51.6%-72.0%) was significantly higher than those with LVEF > 35% (32.1%, 95%-CI: 8.69%-60.7%, p = 0.05). Survival reported in studies from Asia (19.5%, 95%-CI: 13.0%-26.8%) was notably lower than those from Europe (61.0%, 95%-CI: 48.4%-73.0%) and North America (45.5%, 95%-CI: 16.7%-75.8%). GRADE assessment indicated high certainty of evidence for pooled survival. CONCLUSIONS When treated with VA ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock without severe left ventricular depression. VA ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.
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Effects of sodium-glucose cotransporter 1 and 2 inhibitors on cardiovascular and kidney outcomes in type 2 diabetes: A meta-analysis update.
Salah, HM, Al'Aref, SJ, Khan, MS, Al-Hawwas, M, Vallurupalli, S, Mehta, JL, Mounsey, JP, Greene, SJ, McGuire, DK, Lopes, RD, et al
American heart journal. 2021;:86-91
Abstract
In this report, we aim to provide an updated meta-analysis of the sodium-glucose cotransporter 2 (SGLT2) inhibitors trial data with the new trial data on sotagliflozin, a first-in-class dual SGLT1 and SGLT2 inhibitor. We searched Medline, Cochrane library, and Embase databases for randomized clinical trials comparing cardiovascular and kidney outcomes between SGLT2 and dual SGLT1/2 inhibitors and placebo. Nine randomized clinical trials with a total of 60,914 patients with type 2 diabetes were included. In patients with type 2 diabetes, the use of SGLT2 and dual SGLT1/2 inhibitors improves the cardiovascular and kidney outcome.
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Gliflozins for the prevention of stroke in diabetes and cardiorenal diseases: A meta-analysis of cardiovascular outcome trials.
Zhao, LM, Huang, JN, Qiu, M, Ding, LL, Zhan, ZL, Ning, J
Medicine. 2021;(39):e27362
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Abstract
BACKGROUND Individual randomized trials are not powered to assess the relationship between use of sodium-glucose transporter 2 inhibitors and risk of stroke. We sought to explore this issue by a meta-analysis incorporating relevant trials including several latest trials. METHODS Cardiovascular outcome trials of gliflozins were included. Primary outcome was stroke, while secondary outcome was major adverse cardiovascular events (MACE), which was a composite of stroke, myocardial infarction, or cardiovascular death. Meta-analysis was conducted stratified by with/without chronic kidney disease (CKD), with/without heart failure (HF), and with/without atherosclerotic cardiovascular disease (ASCVD), and stratified by different gliflozins. RESULTS We included 9 trials in this meta-analysis. Compared with placebo, gliflozins significantly lowered stroke (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.55-0.84) and MACE (HR 0.77, 95% CI 0.69-0.86) in type 2 diabetes (T2D) patients with CKD, but did not significantly affect stroke (HR 1.00, 95% CI 0.86-1.16) and MACE (HR 0.94, 95% CI 0.86-1.02) in T2D patients without CKD. Gliflozins had no significant effects on the stroke risk (HR 0.94, 95% CI 0.82-1.07) in T2D patients regardless of HF status (Psubgroup = .684) and ASCVD status (Psubgroup = .915), but significantly lowered MACE (HR 0.89, 95% CI 0.83-0.96) in T2D patients regardless of HF status (Psubgroup = .428) and ASCVD status (Psubgroup = .423). Canagliflozin (HR 0.84, 95% CI 0.69-1.01) showed the trend of a reduction in the stroke risk versus placebo, and sotagliflozin (HR 0.73, 95% CI 0.54-0.98) significantly lowered the stroke risk; whereas the other 3 gliflozins did not significantly affect that risk. Ertugliflozin (HR 0.97, 95% CI 0.85-1.11) had no significant effects on the MACE risk, whereas the other 4 gliflozins significantly lowered that risk. CONCLUSIONS Gliflozins, especially canagliflozin and sotagliflozin, should be recommended in T2D patients with CKD to prevent stroke. Most gliflozins lower the risk of MACE in T2D patients regardless of HF status and ASCVD status, whereas ertugliflozin is not observed to lower that risk.
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Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome-Wide Interaction Meta-Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies.
McDonough, CW, Warren, HR, Jack, JR, Motsinger-Reif, AA, Armstrong, ND, Bis, JC, House, JS, Singh, S, El Rouby, NM, Gong, Y, et al
Clinical pharmacology and therapeutics. 2021;(3):723-732
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Abstract
We sought to identify genome-wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome-wide antihypertensive drug-single nucleotide polymorphism (SNP) interaction tests for four drug classes (β-blockers, n = 9,195; calcium channel blockers (CCBs), n = 10,511; thiazide/thiazide-like diuretics, n = 3,516; ACE-inhibitors/ARBs, n = 2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta-analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n = 21,267), blood pressure (BP) response in independent ICAPS studies (n = 1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n = 5,115). One signal reached genome-wide significance in the β-blocker-SNP interaction analysis (rs139945292, Interaction P = 1.56 × 10-8 ). rs139945292 was validated through BP response to β-blockers, with the T-allele associated with less BP reduction (systolic BP response P = 6 × 10-4 , Beta = 3.09, diastolic BP response P = 5 × 10-3 , Beta = 1.53). The T-allele was also associated with increased adverse cardiovascular risk within the β-blocker treated patients' subgroup (P = 2.35 × 10-4 , odds ratio = 1.57, 95% confidence interval = 1.23-1.99). The locus showed nominal replication in CHARGE, and consistent directional trends in β-blocker treated African Americans. rs139945292 is an expression quantitative trait locus for the 50 kb upstream gene NTM (neurotrimin). No SNPs attained genome-wide significance for any other drugs classes. Top SNPs were located near CALB1 (CCB), FLJ367777 (ACE-inhibitor), and CES5AP1 (thiazide). The NTM region is associated with increased risk for adverse cardiovascular outcomes and less BP reduction in β-blocker treated patients. Further investigation into this region is warranted.
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Cardiovascular Effects of Chocolate and Wine-Narrative Review.
Sperkowska, B, Murawska, J, Przybylska, A, Gackowski, M, Kruszewski, S, Durmowicz, M, Rutkowska, D
Nutrients. 2021;(12)
Abstract
The consumption of food for pleasure is mainly associated with adverse health effects. This review was carried out to verify recent reports on the impact of chocolate and wine consumption on cardiovascular health, with a particular focus on atherosclerosis. On one side, these products have proven adverse effects on the cardiovascular system, but on the other hand, if consumed in optimal amounts, they have cardiovascular benefits. The submitted data suggest that the beneficial doses are 30-50 g and 130/250 mL for chocolate and wine, respectively, for women and men. The accumulated evidence indicates that the active ingredients in the products under consideration in this review are phenolic compounds, characterized by anti-inflammatory, antioxidant, and antiplatelet properties. However, there are also some reports of cardioprotective properties of other compounds such as esters, amines, biogenic amines, amino acids, fatty acids, mineral ingredients, and vitamins. Our narrative review has shown that in meta-analyses of intervention studies, consumption of chocolate and wine was positively associated with the beneficial outcomes associated with the cardiovascular system. In contrast, the assessment with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) scale did not confirm this phenomenon. In addition, mechanisms of action of bioactive compounds present in chocolate and wine depend on some factors, such as age, sex, body weight, and the presence of additional medical conditions. Patients using cardiovascular drugs simultaneously with both products should be alert to the risk of pharmacologically relevant interactions during their use. Our narrative review leads to the conclusion that there is abundant evidence to prove the beneficial impact of consuming both products on cardiovascular health, however some evidence still remains controversial. Many authors of studies included in this review postulated that well-designed, longitudinal studies should be performed to determine the effects of these products and their components on atherosclerosis and other CVD (Cardiovascular Disease) disease.
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The Effects of Acute Exposure to Prolonged Sitting, With and Without Interruption, on Vascular Function Among Adults: A Meta-analysis.
Paterson, C, Fryer, S, Zieff, G, Stone, K, Credeur, DP, Barone Gibbs, B, Padilla, J, Parker, JK, Stoner, L
Sports medicine (Auckland, N.Z.). 2020;(11):1929-1942
Abstract
BACKGROUND Exposure to acute prolonged sitting can result in vascular dysfunction, particularly within the legs. This vascular dysfunction, assessed using flow-mediated dilation (FMD), is likely the consequence of decreased blood flow-induced shear stress. With mixed success, several sitting interruption strategies have been trialled to preserve vascular function. OBJECTIVES The objectives of this meta-analysis were to (1) assess the effects of acute prolonged sitting exposure on vascular function in the upper- and lower-limb arteries, and (2) evaluate the effectiveness of sitting interruption strategies in preserving vascular function. Sub-group analyses were conducted to determine whether artery location or interruption modality explain heterogeneity. DATA SOURCES Electronic databases (PubMed, Web of Science, SPORTDiscus, and Google Scholar) were searched from inception to January 2020. Reference lists of eligible studies and relevant reviews were also checked. STUDY SELECTION Inclusion criteria for objective (1) were: (i) FMD% was assessed pre- and post-sitting; (ii) studies were either randomised-controlled, randomised-crossover, or quasi-experimental trials; (iii) the sitting period was ≥ 1 h; and (iv) participants were healthy non-smoking adults (≥ 18 years), and free of vascular-acting medication and disease at the time of testing. Additional inclusion criteria for objective (2) were: (i) the interruption strategy must have been during the sitting period; (ii) there was a control (uninterrupted sitting) group/arm; and (iii) the interruption strategy must have involved the participants actively moving their lower- or upper-limbs. APPRAISAL AND SYNTHESIS METHODS One thousand eight hundred and two articles were identified, of which 17 (22 trials, n = 269) met inclusion criteria for objective (1). Of those 17 articles, 6 studies (9 trials, n = 127) met the inclusion criteria for objective (2). Weighted mean differences (WMD), 95% confidence intervals (95% CI), and standardised mean difference (SMD) were calculated for all trials using random-effects meta-analysis modelling. SMD was used to determine the magnitude of effect, where < 0.2, 0.2, 0.5, and 0.8 was defined as trivial, small, moderate, and large respectively. RESULTS (1) Random-effects modelling showed uninterrupted bouts of prolonged sitting resulted in a significant decrease in FMD% (WMD = - 2.12%, 95% CI - 2.66 to - 1.59, SMD = 0.84). Subgroup analysis revealed reductions in lower- but not upper-limb FMD%. (2) Random-effects modelling showed that interrupting bouts of sitting resulted in a significantly higher FMD% compared to uninterrupted sitting (WMD = 1.91%, 95% CI 0.40 to 3.42, SMD = 0.57). Subgroup analyses failed to identify an optimum interruption strategy but revealed moderate non-significant effects for aerobic interventions (WMD = 2.17%, 95% CI - 0.34 to 4.67, SMD = 0.69) and simple resistance activities (WMD = 2.40%, 95% CI - 0.08 to 4.88, SMD = 0.55) and a trivial effect for standing interruptions (WMD = 0.24%, 95% CI - 0.90 to 1.38, SMD = 0.16). CONCLUSIONS Exposure to acute prolonged sitting leads to significant vascular dysfunction in arteries of the lower, but not upper, limbs. The limited available data indicate that vascular dysfunction can be prevented by regularly interrupting sitting, particularly with aerobic or simple resistance activities.
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To beer or not to beer: A meta-analysis of the effects of beer consumption on cardiovascular health.
Spaggiari, G, Cignarelli, A, Sansone, A, Baldi, M, Santi, D
PloS one. 2020;(6):e0233619
Abstract
A moderate alcohol consumption is demonstrated to exert a protective action in terms of cardiovascular risk. Although this property seems not to be beverage-specific, the various composition of alcoholic compounds could mediate peculiar effects in vivo. The aim of this study was to evaluate potential beer-mediated effects on the cardiovascular health in humans, using a meta-analytic approach (trial registration number: CRD42018118387). The literature search, comprising all English articles published until November, 30th 2019 in EMBASE, PubMed and Cochrane database included all controlled clinical trials evaluating the cardiovascular effects of beer assumption compared to alcohol-free beer, water, abstinence or placebo. Both sexes and all beer preparations were considered eligible. Outcome parameters were those entering in the cardiovascular risk charts and those related to endothelial dysfunction. Twenty-six trials were included in the analysis. Total cholesterol was significantly higher in beer drinkers compared to controls (14 studies, 3.52 mg/dL, 1.71-5.32 mg/dL). Similar increased levels were observed in high-density lipoprotein (HDL) cholesterol (18 studies, 3.63 mg/dL, 2.00-5.26 mg/dL) and in apolipoprotein A1 (5 studies, 0.16 mg/dL, 0.11-0.21 mg/dL), while no differences were detected in low density lipoprotein (LDL) cholesterol (12 studies, -2.85 mg/dL, -5.96-0.26 mg/dL) and triglycerides (14 studies, 0.40 mg/dL, -5.00-5.80 mg/dL) levels. Flow mediated dilation (FMD) resulted significantly higher in beer-consumers compared to controls (4 studies, 0.65%, 0.07-1.23%), while blood pressure and other biochemical markers of inflammation did not differ. In conclusion, the specific beer effect on human cardiovascular health was meta-analysed for the first time, highlighting an improvement of the vascular elasticity, detected by the increase of FMD (after acute intake), and of the lipid profile with a significant increase of HDL and apolipoprotein A1 serum levels. Although the long-term effects of beer consumption are not still understood, a beneficial effect of beer on endothelial function should be supposed.
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Pleiotropic effects of antidiabetic agents on renal and cardiovascular outcomes: a meta-analysis of randomized controlled trials.
Chewcharat, A, Takkavatakarn, K, Isaranuwatchai, S, Katavetin, P, Praditpornsilpa, K, Eiam-Ong, S, Susantitaphong, P
International urology and nephrology. 2020;(9):1733-1745
Abstract
BACKGROUND This meta-analysis was conducted to examine the pleiotropic effects of all available antidiabetic agents except insulin for type 2 diabetes on renal and cardiovascular outcomes. METHODS A systematic literature search was performed in PubMed, EMBASE, and Cochrane database to identify randomized-controlled trials which compared the effectiveness between all antidiabetic agents apart from insulin regarding all aspects of renal and cardiovascular outcomes. Random effect model was utilized to compute for hazard ratio. RESULTS Nineteen articles with 140,851 participants were included in this meta-analysis. When compared with placebo, SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors exhibited significantly lower hazard ratios of progression of albuminuria. SGLT-2 inhibitors and DPP-4 inhibitors showed a significantly higher hazard ratio of regression of albuminuria. Only SGLT-2 inhibitors illustrated significantly lower hazard ratios of doubling of serum creatinine and incidence of renal replacement therapy (RRT). A significantly lower hazard ratio of composite renal outcome was detected in both SGLT-2 inhibitors and GLP-1 agonists. A significantly lower hazard ratio of all-cause mortality was identified in SGLT-2 inhibitors and GLP-1 agonist. Furthermore, a significantly lower hazard ratio of cardiovascular mortality was found in both SGLT-2 inhibitors and GLP-1 agonists. CONCLUSION Comparing across all antidiabetic agents apart from insulin, SGLT-2 inhibitors provided extensively renoprotective effects among diabetic patients as well as reduced hazard ratios of heart failure, cardiovascular mortality, and all-cause mortality. GLP-1 agonists yielded benefits regarding progression of albuminuria, composite renal outcome, and cardiovascular and all-cause mortalities. DPP-4 inhibitors offered only renal protection including progression and regression of albuminuria.
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Cardiovascular effects of waterpipe smoking: a systematic review and meta-analysis.
Al Ali, R, Vukadinović, D, Maziak, W, Katmeh, L, Schwarz, V, Mahfoud, F, Laufs, U, Böhm, M
Reviews in cardiovascular medicine. 2020;(3):453-468
Abstract
Waterpipe smoking has developed into a major and rapidly growing global tobacco epidemic affecting more than 100 million people worldwide. This study identifies and analyzes comprehensively all available data on the cardiovascular effects of waterpipe smoking. Databases PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for studies published until December 2019 assessing cardiovascular effects of waterpipe smoking. We included experimental, cohort, cross-sectional and case-control studies and excluded systematic reviews, case reports/series and qualitative studies. Studies not conducted in humans or not distinguishing waterpipe smoking from other forms of smoking were also excluded. A total of 42 studies with 46 cardiovascular parameters were eligible for analysis. The meta-analysis included 31 studies with 38,037 individuals. Results showed that one waterpipe smoking session leads to immediate increases in heart rate and blood pressure (P < 0.001). Compared to non-smokers, waterpipe smokers had significantly lower high-density lipoprotein levels (P < 0.001), higher levels of low-density lipoprotein (P = 0.04), triglyceride (P < 0.001) and fasting blood glucose (P = 0.03) and higher heart rate (P = 0.04) with a tendency to have higher blood pressure. Mean heart rate, blood pressure and lipids levels did not differ between waterpipe and cigarette smokers, except for total cholesterol, being higher among waterpipe smokers (P < 0.001). Current level of evidence suggests that waterpipe smoking is associated with substantial adverse effects on cardiovascular system, which seem to be similar to those of cigarette smoking. Longitudinal studies are required to scrutinize the magnitude of these effects.