[Show abstract][Hide abstract] ABSTRACT: To investigate the association between commonly used insulin resistance indices and presence and extent of carotid and femoral atherosclerosis in a general population setting.
Cross--sectional analysis of 762 volunteers from the ongoing epidemiological Cyprus Study (46.6% male; mean age=60.5±10.2). (a) Carotid intima--media thickness (IMTcc), (b) carotid and femoral atherosclerotic plaque presence, (c) total plaque area in the carotid/femoral bifurcations (sum of the largest plaques in each carotid/femoral bifurcation--SPAcar/fem) and (d) total plaque area in both carotid and femoral bifurcations (sum of the areas of the largest plaques present in each of the four bifurcations--SPA) were measured using ultrasound at baseline. The HOMA--IR, QUICKI and McAuley indices as well as fasting insulin levels were estimated and their quartiles were used in linear and logistic regression analysis.
All insulin resistance indices studied were strongly associated with IMTcc (p<0.01for all) even after adjustment for age and sex and exclusion of diabetic subjects. However, when looking at plaque presence and size (i.e.area) only the HOMA--IR and especially the McAuley indexwere associated with both carotid plaque presence (OR adj = 1.17;; 95%CI=1.01 to 1.36; p=0.03 and OR adj = 0.86;; 95%CI=0.74 to 0.99;; p=0.04 respectively) and area(OR adj = 0.10; 95%CI=0.008 to 0.20; p=0.03 and OR adj = --0.11; 95%CI=--0.20 to --0.009; p=0.03 respectively), after adjustment.The McAuley index remained a significant predictor of both carotid plaque presence and area even after exclusion of diabetic subjects (p=0.04).
Our results show that while all indices were associated with carotid IMT, supporting a strong role for insulin resistance in intimal--medial thickening, only the HOMA--IR and especially the McAuley indexwere associated with both carotid plaque presence and area, after adjustment. This highlights the importance of including triglyceride levels in estimating the risk for atherosclerotic plaque in the carotids as well as the possible differences in determinants for atherosclerosis between arterial sites.
International angiology: a journal of the International Union of Angiology 02/2015; 34(5). · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
[Show abstract][Hide abstract] ABSTRACT: Peripheral arterial disease (PAD) is one of the most frequent manifestations of atherosclerosis and is associated with atherosclerosis in the coronary and carotid arteries, leading to a highly increased incidence of cardiovascular events. Major risk factors of PAD are similar to those that lead to atherosclerosis in other vascular beds. However, there are differences in the power of individual risk factors in the different vascular territories. Cigarette smoking and diabetes mellitus represent the greatest risks of PAD. For prevention of the progression of PAD and accompanying cardiovascular events similar preventative measures are used as in coronary artery disease (CAD). However, recent data indicate that there are some differences in the efficacy of drugs used in the prevention of atherothrombotic events in PAD. Antiplatelet treatment is indicated in virtually all patients with PAD. In spite of the absence of hard evidence-based data on the long term efficacy of aspirin, it is still considered as a first line treatment and clopidogrel as an effective alternative. The new antiplatelet drugs ticagrelol and prasugrel also represent promising options for treatment of PAD. Statin therapy is indicated to achieve the target low density lipoprotein cholesterol level of ≤ 2.5 mmol/L (100 mg/dL) and there is emerging evidence that lower levels are more effective. Statins may also improve walking capacity. Antihypertensive treatment is indicated to achieve the goal blood pressure (<140/90 mmHg). All classes of antihypertensive drugs including beta-blockers are acceptable for treatment of hypertension in patients with PAD. Diabetic patients with PAD should reduce their glycosylated haemoglobin to ≤ 7.0%. As PAD patients represent the group with the highest risk of atherothrombotic events, these patients need the most intensive treatment and elimination of risk factors of atherosclerosis. These measures should be as comprehensive as those in patients with established coronary and cerebrovascular disease.
International angiology: a journal of the International Union of Angiology 06/2014; 34(1). · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim:
The aim of the study was to test the association between circulating levels of matrix prometalloproteinase1 (pro-MMP1) and its tissue inhibitors TIMP1 and TIMP2 with prevalent cardiovascular events.
Prevalent cardiovascular events were documented in 500 participants of the Cyprus study (46% men) over the age of 40. Serum levels of pro-MMP1, TIMP1 and TIMP2 were measured with ELISA and the association between quartiles of serum levels and presence of cardiovascular disease (CVD) was tested using multivariable binary regression models.
Lower serum levels of pro-MMP1 and TIMP1 were strongly associated with presence of CVD at baseline even after adjustment for conventional risk factors (P(for trend)=0.006 and P=0.001, respectively) and inflammatory factors (P(for trend)=0.005 and P=0.002, respectively) with people in the highest quartile of pro-MMP1 having a reduced odds for cardiovascular disease by about 70% compared to the lowest quartile (OR(adjusted)=0.26; 95% CI=0.19 to 0.75; P=0.01), whereas people with TIMP1 levels >1000 ng/mL had a 75% reduced odds for CVD compared to the rest (OR(adjusted)=0.25; 95% CI=0.11 to 0.60; P(for trend)=0.002). TIMP2 levels were not associated with prevalent cardiovascular disease.
A strong association between lower levels of circulating pro-MMP1 and TIMP1 and risk of prevalent cardiovascular disease in a general population cohort over 40 years is evident, independent from common cardiovascular and inflammatory risk factors. The role of MMP1 and its tissue inhibitors, should be tested further in prospective studies of cardiovascular disease.
International angiology: a journal of the International Union of Angiology 12/2013; 32(6):599-604. · 0.83 Impact Factor