Abstract Background Among high cardiovascular (CV) risk patients, there is emerging need to recognize those who will benefit from new treatments targeting residual risk. Readily available modalities providing reclassification value would be clinically useful in this setting. Preliminary data suggest that carotid ultrasonography using plaque burden but not intima-media thickness (IMT) is associated with very high risk. Objectives We aimed to assess the reclassification ability of two markers of carotid atherosclerosis in high-risk patients, reflecting total atherosclerotic burden and the most severe lesion and to compare them with the routinely used carotid indices IMT and number of carotid plaques. Methods In an ongoing registry of patients who visited a cardiovascular protection clinic for cardiovascular risk assessment, we enrolled 735 consecutively recruited patients (mean age 63.1 years, 68.8% male) classified as high or very-high CV risk according to 2019 European Society of Cardiology /European Atherosclerosis Society Guidelines. Sum of carotid wall thickness (sumWT) and maximal wall thickness (maxWT) using high-resolution ultrasonography at baseline were used to assess the total burden and the most severe carotid lesion, respectively. These markers integrate maximum plaque height or maximum IMT if no plaque is present. All patients were followed for a median of 41 months and the primary end-point consisted of CV mortality, acute myocardial infarction or coronary revascularization. Results After adjustment for traditional CV risk factors, maxWT and sumWT were associated with the primary end-point (hazard ratio [HR]=1.73 (95% confidence interval [CI]:1.39 to 2.17) and 1.19 (95% CI 1.10 to 1.30) respectively). Both markers were superior in terms of reclassification and discrimination to identify very high risk over validated CV risk scores including the Heartscore and the SMART score (net reclassification index [NRI]=0.624, p<0.0001, integrated discrimination index [IDI]=0.060, p<0.0001 and difference in the area under the curve (δAUC) = 0.136, p<0.001 for maxWT and NRI=0.497, p<0.0001, IDI=0.046, p<0.0001 and δAUC = 0.128, p<0.001 for sumWT), IMT (NRI=0.502, p<0.0001, IDI= 0.058, p=0.02 for maxWT and NRI=0.559, p<0.0001, IDI=0.051, p=0.016 for sumWT) and the number of carotid plaques (NRI=0.614, p<0.0001, IDI=0.038, p=0.001 for maxWT and NRI=0.292, p=0.019, IDI=0.022, p=0.009 for sumWT). Conclusions The use of two novel cumulative markers of atherosclerotic burden improves risk stratification and discriminates high from very high CV risk. Given that carotid ultrasonography is a readily available modality, its clinical application for risk refinement of high-risk patients to facilitate treatment decisions merits further investigation. Funding Acknowledgement Type of funding sources: None.
Abstract Circulating amyloid-beta 1–40 (Αb40) has pro-atherogenic properties and could serve as a biomarker in atherosclerotic cardiovascular disease (ASCVD). However, the association of Ab40 levels with morphological characteristics reflecting atherosclerotic plaque echolucency and composition is not available. Carotid atherosclerosis was assessed in consecutively recruited individuals without ASCVD ( n = 342) by ultrasonography. The primary endpoint was grey scale median (GSM) of intima-media complex (IMC) and plaques, analysed using dedicated software. Vascular markers were assessed at two time-points (median follow-up 35.5 months). In n = 56 patients undergoing carotid endarterectomy, histological plaque features were analysed. Plasma Αb40 levels were measured at baseline. Ab40 was associated with lower IMC GSM and plaque GSM and higher plaque area at baseline after multivariable adjustment. Increased Ab40 levels were also longitudinally associated with decreasing or persistently low IMC and plaque GSM after multivariable adjustment ( p < 0.05). In the histological analysis, Ab40 levels were associated with lower incidence of calcified plaques and plaques without high-risk features. Ab40 levels are associated with ultrasonographic and histological markers of carotid wall composition both in the non-stenotic arterial wall and in severely stenotic plaques. These findings support experimental evidence linking Ab40 with plaque vulnerability, possibly mediating its established association with major adverse cardiovascular events.
Objective: Chios mastic is a natural nutritional supplement consisting of several bioactive compounds and it possesses antioxidant and anti-inflammatory activities. Preliminary recent evidence suggests an anti-hypertensive effect of mastic. HYPER-MASTIC is a double-blind, randomized and controlled clinical trial, with the aim of investigating the additional effect of a three-month supplementation with Chios mastic on arterial hypertension of Greek patients with well-managed cardiovascular risk factors. Design and method: Patients with well controlled hypertension are being consecutively recruited and randomly allocated into three groups of supplements: 1500mg of mastic, 2800 mg of mastic and placebo in this ongoing study. For the current analyses, the two mastic groups were merged. Blood pressure measurements, using both office and 24h blood pressure measurement, and blood tests were performed at baseline and at 3 months. Flow-mediated dilatation (FMD) at the level of the brachial artery was measured in all patients as a measure of endothelial function. Patients reported no recent history of acute myocardial infarction or stroke and no history of heart failure. Herein, the preliminary results of the study are presented. Results: At the time of analysis, twenty one patients [48% females, age: 62 (14)] were consecutively recruited and randomized, with available data at 3 months. Thirteen volunteers were allocated to mastic and eight to placebo. No difference was found regarding age, sex distribution, BMI levels, personal or family history of hyperlipidemia and hypertension, diabetes mellitus type 2 and coronary artery disease between the two groups. Patients in the mastic group reduced their night-time diastolic blood pressure compared to placebo [-5 (10) vs -2.5 (16.3) mmHg | p = 0.025, respectively]. No other differences from placebo were observed on the effect of mastic on BP parameters. FMD dropped with time in the placebo group, whereas in the mastic group it was preserved [-1.2 (2.7) vs -0.2 (0.8) | pinteraction = 0.010]. Conclusions: Chios mastic supplementation leads to improved night-time diastolic blood pressure and preserved endothelial function in patients with well-controlled hypertension, suggesting that it may incrementally exert anti-hypertensive and vasculoprotective properties over anti-hypertensive medication.
Summary The genomic control (GC) approach is extensively used to effectively control false positive signals due to population stratification in genome-wide association studies (GWAS). However, GC affects the statistical power of GWAS. The loss of power depends on the magnitude of the inflation factor ( λ ) that is used for GC. We simulated meta-analyses of different GWAS. Minor allele frequency (MAF) ranged from 0·001 to 0·5 and λ was sampled from two scenarios: (i) random scenario (empirically-derived distribution of real λ values) and (ii) selected scenario from simulation parameter modification. Adjustment for λ was considered under single correction (within study corrected standard errors) and double correction (additional λ corrected summary estimate). MAF was a pivotal determinant of observed power. In random λ scenario, double correction induced a symmetric power reduction in comparison to single correction. For MAF <5%, GC significantly reduced power for genetic risks ranging from 1·2 to 1·4 (n = 10–20). Rising MAF attenuated the correction effect of λ adjustment. Moderate λ approach yielded more conservative results for population stratification adjustment, especially for MAF <5%. Large λ approach yielded an approximate two fold decrease in power when compared to moderate λ approach and almost four fold when the original random λ scenario was considered. Meta-analysis power can be adequate to detect significant variants even for double GC correction when effect size exceeds >1·2 and MAF >5%. Our results provide a quick but detailed index for power considerations of future meta-analyses of GWAS that enables a more flexible design from early steps based on the number of studies accumulated in different groups and the λ values observed in the single studies.
Introduction: Ischemic mitral regurgitation (IMR) is considered a ventricular myocardial disease caused by local remodeling after an acute myocardial infarction (AMI) of inferolateral location.There are very few studies that evaluate the factors that influence the progression of IMR.Left atrium (LA) dilatation may negatively affect to atrial and ventricular remodeling.Our aim is to determine the impact of LA dilatation at the time of AMI on the maintenance or progression of IMR after coronary revascularization and its probable relation with major adverse cardiovascular events (MACE).Methods: We included 126 patients (79.4% male; mean age of 62.8±13.8years) with AMI whose responsible vessel was the circumflex artery (Cx).All the patients underwent an echocardiogram at admission and after 6 months in which we analyzed: the LA area and volume variables, the degree of mitral regurgitation, the effective regurgitant orifice (ERO) and left ventricular ejection fraction (LVEF).Patients with chronic mitral valve disease, calcified mitral valves and whose mitral valvular disease may be of organic origin were excluded.We evaluated the association between LA dilatation at the first echocardiogram with the echocardiographic data at 6-month and with MACE rate after a mean follow-up of 36 months (death from any cause, cardiac death, readmission for heart failure (HF) and stroke).Results: Clinical presentation was STEMI in 43.7% and NSTEMI in 56.3%.29.8% were diabetic and 61.3% had hypertension.All patients were revascularized by PCI during admission.We used the IMR classification with severity criteria for ERO>0.20 cm 2 .85 patients (69.6%) developed a certain degree of IMR during admission, being severe in 32 of them (26.2%).Patients with a dilated LA, even of a mild degree, had more severe IMR at admission and at 6 months (47% vs 3,3% and 46% vs 8,3% p<0.001).LA dilatation was also associated with higher mortality from any cause (14% vs 1.6%, p<0.001), cardiovascular mortality (10% vs 1.6%, p<0.001) readmissions for HF (28% vs. 8.4%, p<0.001).There were not significant difference regarding stroke rate (1,6% vs 9,6% p<0.17) compared to those with normal LA.The MACE rate was also higher in patients with dilated LA at admission (31.0%vs 10%, p<0.001) Conclusions: Patients with a dilated LA at the time of an AMI, even of a mild degree, have a higher rate of severe IMR both at admission and at 6 months, worse LVEF and a higher MACE rate.Although IMR is considered to be a ventricular myocardial disease, remodeling at LA level seems to play a role in its reversibility and could serve as a prognostic marker for this group of patients.
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