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Comparison of statins for primary prevention of cardiovascular disease and persistent physical disability in older adults.
Zhou, Z, Curtis, AJ, Ernst, ME, Ryan, J, Zoungas, S, Wolfe, R, McNeil, JJ, Murray, AM, Reid, CM, Chowdhury, EK, et al
European journal of clinical pharmacology. 2022;(3):467-476
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Abstract
PURPOSE Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD) events and persistent physical disability in healthy older adults. However, the comparative efficacy of different statins in this group remains unclear. This study aimed to compare different forms of statins in their associations with CVD and physical disability in healthy older adults. METHODS This post hoc analysis included data from 5981 participants aged ≥ 70 years (≥ 65 if US minorities; median age:74.0) followed for a median of 4.7 years, who had no prior CVD events or physical disability and reported using a statin at baseline. The incidence of the composite and components of major adverse cardiovascular events and persistent physical disability were compared across different statins according to their type, potency, and lipophilicity using multivariable Cox proportional-hazards models. RESULTS Atorvastatin was the most used statin type at baseline (37.9%), followed by simvastatin (29.6%), rosuvastatin (25.5%), and other statins (7.0%, predominantly pravastatin). In comparisons of specific statins according to type and lipophilicity (lipophilic vs. hydrophilic statin), observed differences in all outcomes were small and not statistically significant (all p values > 0.05). High-potency statin use (atorvastatin and rosuvastatin) was marginally associated with lower risk of fatal CVD events compared with low-/moderate-potency statin use (hazard ratio: 0.59; 95% confidence interval: 0.35, 1.00). CONCLUSION There were minimal differences in CVD outcomes and no significant difference in persistent physical disability between various forms of statins in healthy older adults. Future investigations are needed to confirm our results.
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Differential effects of renin-angiotensine-aldosteron system inhibition, sympathoinhibition and low sodium diet on blood pressure in women with a history of preeclampsia: A double-blind, placebo-controlled cross-over trial (the PALM study).
Zoet, GA, Paauw, ND, Veerbeek, JHW, Groenhof, TKJ, Spiering, W, Verhaar, MC, Franx, A, Titia Lely, A
Pregnancy hypertension. 2022;:173-175
Abstract
Current guidelines lack sufficient evidence to recommend a specific blood pressure lowering strategy to prevent cardiovascular disease after preeclampsia. We conducted a double-blind cross-over trial to identify the most potent antihypertensive strategy: renin-angiotensin-aldosterone system (RAAS) inhibition (losartan), sympathoinhibition (moxonidine), low sodium diet and placebo (n = 10). Due to low inclusion rate our study stopped prematurely. Initiatory analyses showed no significant effect of antihypertensive strategy on office blood pressure and 24-hour blood pressure. However, nocturnal dipping was significantly higher on RAAS inhibition and low sodium diet compared to placebo and sympathoinhibition. Optimal cardiovascular prevention after preeclampsia should be further explored.
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Hypertension- and glycaemia-lowering effects of a grape-pomace-derived seasoning in high-cardiovascular risk and healthy subjects. Interplay with the gut microbiome.
Taladrid, D, de Celis, M, Belda, I, Bartolomé, B, Moreno-Arribas, MV
Food & function. 2022;(4):2068-2082
Abstract
Purpose: Grape pomace (GP) is a winery by-product rich in polyphenols and dietary fibre. Some recent results suggest that GP-derived extracts could be promising additives in food, specially recommended for low-salt diets. The hypothesis tested in this paper is that the regular consumption of GP-derived seasonings could help in the control of hypertension and glycaemia. Methods: A randomized intervention study (6 weeks) was performed in high-risk cardiovascular subjects (n = 17) and in healthy subjects (n = 12) that were randomly allocated into intervention (2 g day-1 of GP seasoning) or control (no seasoning consumed) groups. Blood samples, faeces, urine and blood pressure (BP) were taken at the baseline and at the end of the intervention. Faecal samples were analysed for microbiota composition (16S rRNA gene sequencing) and microbial-derived metabolites (short chain fatty acids and phenolic metabolites). Results: Among the clinical parameters studied, BP and fasting blood glucose significantly decreased (p < 0.05) after the seasoning intervention, but not for the control group. Notably, application of a novel approach based on ASV (Amplicon Sequence Variant) co-occurrence networks allowed us to identify some bacterial communities whose relative abundances were related with metadata. Conclusion: Our primary findings suggest that GP-seasoning may help in the modulation of cardiometabolic risk factors, mainly in the early stages. Furthermore, it evidences modulation of gut microbiota and functional bacterial communities by grape pomace, which might mediate the cardiometabolic effects of this by-product.
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Effects of vegetarian versus Mediterranean diet on kidney function: Findings from the CARDIVEG study.
Dinu, M, Colombini, B, Pagliai, G, Giangrandi, I, Cesari, F, Gori, A, Giusti, B, Marcucci, R, Sofi, F
European journal of clinical investigation. 2021;(9):e13576
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Abstract
BACKGROUND The aim of the present study was to assess the effects of a lacto-ovo-vegetarian diet (VD), compared to a Mediterranean diet (MD), on kidney function in a group of subjects with medium-to-low cardiovascular risk profile. METHODS We analysed 107 subjects (82 women, 25 men; median age 52) who followed a VD (n = 54) and a MD (n = 53) for 3 months in the CARDIVEG study, a randomized, open, crossover trial that compared the effects of these 2 diets on cardiovascular disease risk. RESULTS The effect of the two diets on kidney function markers was evaluated by conducting a general linear model for repeated measurements adjusted for possible confounding factors such as age, sex, physical activity, alcohol, smoking, hypertension, LDL cholesterol, glucose and body weight change. A significant reduction in creatinine (-5.3%; P < .001), urea nitrogen levels (-9%; P = .001), blood urea nitrogen (BUN) (-8.7%; P = .001) and BUN/creatinine ratio (-5.8%; P < .001), and an increase in estimated glomerular filtration rate (eGFR) (+3.5%; P = .001) was observed during the VD period. On the contrary, no significant changes were noted in the MD group. Variations obtained in the two dietary interventions were significantly different (P < .0001) for creatinine levels, BUN/creatinine and eGFR, for which opposite trends were observed in the VD and MD groups. CONCLUSIONS In a selected group of subjects with medium-to-low cardiovascular risk profile, a 3 month VD period determined significant improvements in kidney function markers. Further trials are needed to confirm these results.
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Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy: Secondary Analysis From the FOURIER Randomized Clinical Trial.
Deedwania, P, Murphy, SA, Scheen, A, Badariene, J, Pineda, AL, Honarpour, N, Keech, AC, Sever, PS, Pedersen, TR, Sabatine, MS, et al
JAMA cardiology. 2021;(2):139-147
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Abstract
IMPORTANCE The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER randomized clinical trial. Patients with metabolic syndrome (MetS) are at increased cardiovascular risk. OBJECTIVE To investigate outcomes with evolocumab in patients with and without MetS. DESIGN, SETTING, AND PARTICIPANTS The FOURIER trial randomized patients worldwide with stable atherosclerotic cardiovascular disease receiving statin to evolocumab vs placebo with follow-up for a median of 2.2 years. Data were collected February 2013 to November 2016. For this prespecified analysis, patients with the requisite data were stratified based on the National Cholesterol Education Program Adult Treatment Panel III MetS criteria; in secondary analyses, patients were further substratified by diabetes at baseline. Analysis was intention to treat. Analysis began March 2018 and ended April 2020. INTERVENTIONS Patients were randomized to evolocumab or placebo. MAIN OUTCOMES AND MEASURES The primary end point was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point was cardiovascular death, myocardial infarction, or stroke. RESULTS Of 27 342 patients (mean [SD] age, 63 [9] years; 20 623 men [75.4%]) included in this analysis, 16 361 (59.8%) with baseline MetS were, when compared with patients without MetS, at higher risk of cardiovascular events (adjusted hazard ratio [95% CI], 1.31 [1.18-1.46]; P < .001 for the primary and 1.38 [1.20-1.57]; P < .001 for the key secondary end point). Evolocumab reduced low-density lipoprotein cholesterol similarly in patients with MetS (median [interquartile range], 92 [79-109] mg/dL vs 30 [19-48] mg/dL; P < .001) and without MetS (median [interquartile range], 92 [81-108] mg/dL vs 29 [18-44] mg/dl; P < .001). For the primary end point, the hazard ratios (95% CI) with evolocumab vs placebo were 0.83 (0.76-0.91) and 0.89 (0.79-1.01) in patients with and without MetS (P for interaction = .39). For the key secondary end point, the corresponding hazard ratios (95% CIs) were 0.76 (0.68-0.86) and 0.86 (0.74-1.01) (P for interaction = .23), respectively. Evolocumab did not increase the risk of new-onset diabetes or other major safety outcomes including worsening glycemic control, compared with placebo in patients with MetS. CONCLUSIONS AND RELEVANCE Patients with atherosclerotic cardiovascular disease and MetS have substantial residual risk of cardiovascular events despite statin therapy. Evolocumab significantly reduced low-density lipoprotein cholesterol and cardiovascular risk in patients with MetS without increasing new-onset diabetes, worsening glycemic control, or other major safety events. These data suggest the addition of evolocumab to statin therapy in patients with atherosclerotic cardiovascular disease and MetS is safe and efficacious to reduce residual cardiovascular risk. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01764633.
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Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease.
Chertow, GM, Vart, P, Jongs, N, Toto, RD, Gorriz, JL, Hou, FF, McMurray, JJV, Correa-Rotter, R, Rossing, P, Sjöström, CD, et al
Journal of the American Society of Nephrology : JASN. 2021;(9):2352-2361
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BACKGROUND In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized, placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or without type 2 diabetes. METHODS Adults with eGFR of 25-75 ml/min per 1.73 m2 and urinary albumin-to-creatinine ratio of 200-5000 mg/g had been randomized to receive dapagliflozin 10 mg/d or placebo. Here, we conducted a prespecified analysis of dapagliflozin's effects in patients with stage 4 CKD (eGFR,30 ml/min per 1.73 m2) at baseline. The primary end point was a composite of time to ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Secondary end points were a kidney composite (same as the primary end point but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. RESULTS A total of 293 participants with stage 4 CKD received dapagliflozin and 331 received placebo. Patients with stage 4 CKD randomized to dapagliflozin experienced a 27% (95% confidence interval [95% CI]: -2 to 47%) reduction in the primary composite endpoint, and 29% (-2 to 51%), 17% (-53 to 55%), and 32% (-21 to 61%) reductions in the kidney, cardiovascular and mortality endpoints, respectively, relative to placebo. Interaction P-values were 0.22, 0.13, 0.63, and 0.95, respectively, comparing CKD stages 4 versus 2/3. The eGFR slope declined by 2.15 and 3.38 ml/min per 1.73 m2 per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. CONCLUSIONS Among patients with stage 4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.
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Pharmacodynamic study of the cardiovascular polypill. Is there any interaction among the monocomponents?
González-Juanatey, JR, Tamargo, J, Torres, F, Weisser, B, Oudovenko, N
Revista espanola de cardiologia (English ed.). 2021;(1):51-58
Abstract
INTRODUCTION AND OBJECTIVES To compare the pharmacodynamics of the CNIC polypill (atorvastatin 40mg/ramipril 10mg/aspirin 100mg) in terms of low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP), with the corresponding reference products (atorvastatin and ramipril). METHODS This was a multicenter, randomized, open-label, and parallel 3-arm study comparing the effect of the CNIC polypill vs ramipril 10mg and atorvastatin 40mg on SBP and LDL-C. The coprimary endpoints were differences in the adjusted mean 24-hour SBP (using ambulatory BP measurement) and LDL-C during the study period estimated using an ANCOVA model. RESULTS Of the 241 patients included in the per protocol population, 84 received the CNIC polypill (group A), 84 atorvastatin (group B), and 73 ramipril (group C). SBP decreased from 139.3±12.5 to 133.2±12.9mmHg in group A and from 138.1±11.9 to 134.0±12.8mmHg in group C (baseline adjusted mean difference for the decrease in SBP was 1.77mmHg (90%CI, -0.5 to 4.0) in favor of group A, without reaching statistical significance. LDL-C was reduced by 33.9±21.6 and 29.2±25.8mg/dL in groups A and B, respectively (baseline adjusted mean difference for the decrease in LDL-C was 7.0% (90%CI, 1.5-12.4), a significantly greater decrease with the polypill). The 3 treatments were well tolerated. CONCLUSIONS The results of this study rule out a negative effect on blood pressure of the interaction between the components of the CNIC polypill. The reduction in LDL-C was greater in the CNIC polypill group, suggesting a synergistic effect of the components.
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The effect of concentrated pomegranate juice consumption on risk factors of cardiovascular diseases in women with polycystic ovary syndrome: A randomized controlled trial.
Abedini, M, Ghasemi-Tehrani, H, Tarrahi, MJ, Amani, R
Phytotherapy research : PTR. 2021;(1):442-451
Abstract
Polycystic ovary syndrome (PCOS) is associated with insulin resistance and dyslipidemia. Pomegranate juice is a rich source of polyphenols that may improve blood pressure, lipid profile, and other risk factors of cardiovascular diseases (CVDs). No study has examined the effects of pomegranate juice consumption on the clinical outcomes of PCOS. This study aimed to examine the effects of concentrated pomegranate juice (CPJ) consumption on risk factors of CVDs in women with PCOS. In this randomized clinical trial, 44 PCOS women with an age range of 18-40 years and body mass index (BMI) of ≥25 kg/m2 were recruited. They were randomly allocated to the CPJ (n = 22) and control (n = 22) groups, and followed for 8 weeks. Anthropometric measures, blood pressure, and biochemical parameters were measured at baseline and at the end of the trial. Compared with the control group, CPJ consumption significantly reduced systolic (-9.77 ± 1.46 vs. -1.18 ± 1.46 mmHg, p < .001) and diastolic (-3.87 ± 1.36 vs. 0.30 ± 1.36 mmHg, p = .05) blood pressure, serum triglyceride (TG) levels (-7.82 ± 6.32 vs. 16.63 ± 6.32 mg/dl, p = .01), TG/high-density lipoprotein-cholesterol (HDL-C) ratio (-0.39 ± 0.24 vs. 0.66 ± 0.24, p = .007), and increased serum concentrations of low-density lipoprotein-cholesterol (LDL-C) (6.03 ± 2.47 vs. -1.98 ± 2.47 mg/dl, p = .04) and HDL-C (1.93 ± 1.10 vs. -1.78 ± 1.10 mg/dl, p = .03). These findings were obtained after taking baseline measurements and potential confounders into account. No adverse event or complication was reported due to CPJ consumption throughout the study. We found that CPJ consumption has a beneficial effect on blood pressure, serum concentrations of TG and HDL-C, and TG/HDL-C ratio in women with PCOS. However, this juice could increase serum LDL-C levels in these patients. This trial was registered at www.irct.ir as IRCT20191109045383N1.
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Chocolate consumption and all-cause and cause-specific mortality in a US population: a post hoc analysis of the PLCO cancer screening trial.
Zhong, GC, Hu, TY, Yang, PF, Peng, Y, Wu, JJ, Sun, WP, Cheng, L, Wang, CR
Aging. 2021;(14):18564-18585
Abstract
Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84-0.94], 0.84 (95% CI 0.79-0.90), 0.86 (95% CI 0.81-0.93), and 0.87 (95% CI 0.82-0.93) for >0-0.5 servings/week, >0.5-1 serving/week, >1-2 servings/week, and >2 servings/week, respectively (Ptrend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer's disease. A nonlinear dose-response pattern was found for all-cause and cardiovascular mortality (all Pnonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all Pinteraction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer's disease in this US population.
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Effects of Caloric Restriction and Rope-Skipping Exercise on Cardiometabolic Health: A Pilot Randomized Controlled Trial in Young Adults.
Tang, Z, Ming, Y, Wu, M, Jing, J, Xu, S, Li, H, Zhu, Y
Nutrients. 2021;(9)
Abstract
The aim of this study is to investigate the effects of calorie restriction (CR), rope-skipping (RS) exercise, and their joint effects on cardiometabolic health in young adults. An 8-week randomized trial was conducted on 46 undergraduates aged 19-21 y from South China. The participants were randomized into the following three groups: Calorie restriction (CR) group (n = 14), Rope-skipping (RS) group (n = 14), and CR plus RS (CR-RS) group (n = 12). At both allocation and the end of the intervention, data on anthropometry, serum metabolic, and inflammatory markers were collected. A total of 40 participants completed the intervention and were included in the analysis. After the 8-week intervention, the participants from the CR group and the CR-RS group reduced in body weight (-1.1 ± 1.7 kg, -1.3 ± 2.0 kg), body mass index (-0.4 ± 0.6 kg/m2, -0.5 ± 0.7 kg/m2), body fat percentage (-1.2 ± 1.6%, -1.7 ± 1.8%), and body fat mass (-1.1 kg (-2.2, -0.3), -1.1 kg (-2.5, -0.4)) compared to the baseline (p < 0.05 or p = 0.051). For metabolic and inflammatory factors, the participants in the CR-RS group showed significant decreases in low density lipoprotein cholesterol (-0.40 mmol/L) and interleukin-8 (-0.73 mmol/L). While all the above markers showed no significant difference among the groups after intervention, in the subgroup of overweight/obese participants (n = 23), the CR-RS group had significantly lower blood pressure, fasting insulin, homeostatic model assessment of insulin resistance, tumor necrosis factor-α, and interleukin-8 levels than the CR or RS groups (p < 0.05). In conclusion, both CR and CR-RS could reduce weight and improve body composition in young adults. More importantly, in those with overweight or obesity, CR-RS intervention might be superior to either CR or RS in improving cardiometabolic health.