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Context: Next to a large body of epidemiological observational studies showing that the Mediterranean diet (MD) is an important lifestyle determinant of cardiovascular risk, there is less relevant evidence from well-conducted randomized controlled trials (RCTs) with hard cardiovascular outcomes., Objective: The objective of the study was to identify the most effective dietary intervention for reducing cardiovascular morbidity and mortality., Data Sources: A systematic approach following PRISMA network meta-analyses reporting guidelines was applied to a search of electronic databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Embase) without language restrictions, supplemented by scanning through bibliographies of studies and meetings' abstract material. Inclusion criteria were RCTs conducted in an adult population, investigating the effects of different type of diets or dietary patterns on all-cause mortality and cardiovascular outcomes of interest., Data Extraction: Data extraction for each study was conducted by 2 independent reviewers., Data Analysis: A frequentist network meta-analysis using a random-effects model was conducted. Death from any cardiovascular cause was defined as the primary outcome. A total of 17 trials incorporating 83 280 participants were included in the systematic review. Twelve articles (n = 80 550 participants) contributed to the network meta-analysis for the primary outcome. When compared with the control diet, only the MD showed a reduction in cardiovascular deaths (risk ratio = 0.59; 95% confidence interval, 0.42-0.82). Additionally, MD was the sole dietary strategy that decreased the risk of major cardiovascular events, myocardial infarction, angina, and all-cause mortality., Conclusions: MD may play a protective role against cardiovascular disease and death for primary and also secondary prevention., Systematic Review Registration: Center for Open Science, https://doi.org/10.17605/OSF.IO/5KX83., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Abstract: Lipoprotein(a) [Lp(a)] is a cardiovascular factor, for which there is no approved specific lowering treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to have lowering effects on Lp(a). Aim of this systematic review is to synthesize the current literature and quantify the effects of PCSK9 inhibitors on the serum Lp(a) levels in human subjects. Double-blind, phase 2 or 3, randomized-controlled trials comparing PCSK9 inhibitors (alirocumab or evolocumab) to placebo and/or ezetimibe and/or other lipid-lowering therapy were deemed eligible for inclusion. We searched MEDLINE (via PubMed), CENTRAL, Scopus, and Web of Science as of 17 June 2020. Quality assessment was performed using the Revised Cochrane risk-of-bias tool for randomized trials. Forty-three studies were identified (64,107 patients randomized) and 41 studies were included in the quantitative analysis. PCSK9 inhibitors reduced Lp(a) levels by -26.7% (95% CI, -29.5% to -23.9%) with a significant heterogeneity within studies. There was significant difference in Lp(a) change from baseline according to comparator (placebo: mean -27.9%; 95% CI, -31.1% to -24.6% vs. ezetimibe: mean, -22.2%; 95% CI, -27.2% to -17.2%; P = 0.04) and duration of treatment (≤12 weeks: mean, -30.9%; 95% CI, -34.7% to -27.1% vs. >12 weeks: mean, -21.9%; 95% CI, -25.2% to -18.6%; P < 0.01). Meta-regression analysis showed that only the mean percentage change from baseline low-density lipoprotein cholesterol due to the intervention is significantly associated with the effect size difference (P < 0.0001). PCSK9 inhibitors reduced low-density lipoprotein cholesterol by -54% (95% CI -57.6% to -50.6%). There is substantial efficacy of the currently approved PCSK9 inhibitors in the lowering of Lp(a) levels. Dedicated randomized controlled trials are needed to establish the benefit of this intervention., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a new antihyperglycemic class with the demonstrated advantage of reducing major adverse cardiovascular events (MACE) among individuals with type 2 diabetes (T2DM), atherosclerotic cardiovascular disease, or high cardiovascular risk., Objective: Τo summarize the evidence of systematic reviews (SRs) that assess MACE (cardiovascular mortality, nonfatal myocardial infarction, and stroke) and hospitalizations for heart failure in GLP-1RAs-treated patients and to evaluate possible overlap in pertinent SRs., Methods: We performed a comprehensive search via MEDLINE, Cochrane Library, and PROSPERO databases up to February 23, 2020, for SRs examining cardiovascular outcomes of GLP-1RAs in T2DM patients. Three independent authors extracted data and assessed the methodological quality of the included SRs using the ROBIS tool., Results: We found 37 SRs - published between 2009 and 2020 in English - of which 35 collected data only from randomized clinical trials while two from observational studies as well. The methodological quality of the 37 SRs ranged from low to high, while only 3 have evaluated the overall quality of evidence outcome using the Grading of Recommendations Assessments, Development and Evaluation (GRADE) approach. All the included SRs showed cardiovascular safety of GLP-1RAs while the latest ones demonstrated a reduction in composite MACE endpoint as well as its every individual component and heart failure hospitalizations., Conclusion: In the first overview of SRs about cardiovascular outcomes of GLP-1RAs, they proved favorable effects on reducing cardiovascular events in T2DM patients. There are, however, many overlapping reviews based on relatively few cardiovascular outcomes trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Diabetes mellitus (DM) is an established risk factor for atherosclerotic cardiovascular disease (CVD), and patients with DM are at a two to four-fold higher cardiovascular risk, including myocardial infraction, unstable angina, stroke, and heart failure. All of the above have arisen interest in CVD preventive strategies by the use of non-invasive methods, such as risk scores. The most common approach is to consider DM as a CVD equivalent and, therefore, to treat patients with DM in a similar way to those who required secondary CVD prevention. However, this approach has been disputed as all patients with DM do not have the same risk for CVD, and since other potentially important factors within the context of DM, such as DM duration, presence of albuminuria, and comorbidities, should be taken into consideration. Thus, the second and third approach is the application of risk models that were either developed initially for the general population or designed specifically for patients with DM, respectively. This review summarizes the evidence and implications for clinical practice regarding these scores. Up to date, several models that can be applied to the diabetic population have been proposed. However, only a few meet the minimum requirement of adequate external validation. In addition, moderate discrimination and poor calibration, which might lead to inaccurate risk estimations in populations with different characteristics, have been reported. Therefore, future research is needed before recommending a specific risk model for universal clinical practice in the management of diabetes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Type 1 diabetes is an important risk factor for the development of cardiovascular disease. Pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) measurements are well recognized as independent predictors for future cardiovascular disease. The aim of the present study was to systematically review the literature and conduct a meta-analysis assessing measures of subclinical arterial damage in children and adolescents with type 1 diabetes in comparison to healthy controls., Methods: PubMed and Cochrane Library were searched to identify studies comparing cIMT and carotid-femoral PWV levels between children with type 1 diabetes and healthy controls. Meta-analysis was performed to compare the difference of overall mean cIMT and carotid-femoral PWV levels between the two groups. New Castle Ottawa quality assessment scale for case-control studies was used to assess study quality., Results: Twenty-three studies were finally included in the meta-analysis (20 studies for cIMT and 4 studies for carotid-femoral PWV). Youth with type 1 diabetes had significantly higher cIMT levels than controls (mean difference [d] = 0.03, 95% confidence interval [CI] = 0.02-0.04), as well as higher carotid-femoral PWV levels (d = 0.26, 95% CI = 0.18-0.34). Heterogeneity was present only in the cIMT analysis (I 2  > 90%)., Conclusions: Youth with type 1 diabetes showed signs of subclinical arterial damage, as suggested by higher levels of cIMT and carotid-femoral PWV compared to healthy controls at childhood and adolescence. Preventive and therapeutic interventions early in course of disease may be further studied to decrease morbidity in this high-risk young patient group. PROSPERO registration number: 2018 CRD42018094354., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cardiovascular damage is clinically manifested as coronary artery disease, heart failure, stroke and peripheral artery disease. The prevalence of these adverse conditions is higher with advancing age. Although many patients present cardiovascular damage late in their life, it is common to see patients with early atherosclerosis in cardiovascular intensive care units at ages lower than 50 years in men and 55 for women., Methods and Results: In this review of the literature we identified risk factors of early vascular damage. The classic risk factors such as age, gender, diabetes mellitus, dyslipidemia, smoking, alcohol, hypertension, obesity, family history and newer biomarkers such as hs-CRP, folic acid, homocysteine, fibrinogen are neither strong nor predictive of the individual patient's risk to present early cardiovascular disease. All these risk factors have been used to propose risk scores for possible future events but we still lack a single strong marker indicating new onset of disease that will predict the future independently of the classical factors. The role of vascular imaging techniques to identify patients with subclinical atherosclerotic vascular damage before clinical disease, including the effect of known and unknown risk factors on the vascular tree, seems to be very important for intensifying preventive measures in high risk patients. Early arteriosclerosis measured from pulse wave velocity is associated with reduced arterial elasticity and is associated with future cardiovascular events., Conclusions: Vascular measurements may better represent the continuum of cardiovascular disease from a young healthy to an aged diseased vessel that is going to produce adverse clinical events., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

BACKGROUND This study compared the diagnostic accuracy of blood pressure (BP) measurement methods, office BP, ambulatory BP monitoring (ABPM), and home BP, in the identification of early vascular aging (EVA) and developed a score to predict the risk of EVA in hypertensive patients. METHODS Two-hundred eighty-two consecutive subjects (39.7% male) aged 56.8  ±  15.8 years were included. Office and out-of-office BP measurements including ABPM on a usual working day and 7 days home BP monitoring were performed. Carotid-femoral pulse wave velocity (c-f PWV) was measured in all patients. EVA was defined as c-f PWV values higher than the expected for age average values according to European population data. RESULTS In univariate analysis, EVA was significantly correlated with office systolic BP, average 24-hour systolic and diastolic BP, and average 24-hour and office heart rates. The area under the curve for predicting EVA was 0.624 (95% CI 0.551 to 0.697), 0.559 (95% CI 0.484 to 0.635) and 0.565 (95% CI 0.49 to 0.641), for daytime, home, and office systolic BP, respectively. Ambulatory BP variables, age, sex, body mass index, diabetes mellitus (yes/no), and estimated glomerular filtration rate were used to develop a new score for EVA providing a total accuracy of 0.82, 0.84 sensitivity, and 0.78 specificity. CONCLUSIONS In conclusion, the new risk score, Early Vascular Aging Ambulatory score, may accurately identify hypertensive patients with EVA using ABPM values and classic cardiovascular risk factors. [ABSTRACT FROM AUTHOR]