Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases.

Chronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR) is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL), and arterial stiffness (core feature of arterial aging), as measured by carotid-femoral pulse wave velocity (c-f PWV).The study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis.Through multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001) and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001) and independently negatively associated with LTL (p = 0.0378). HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001) and age (p = 0.0001). In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.These data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk

Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80 Mg Once Daily in Stable Angina Patients in Real-World Practice

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Multiple linear regression analysis of LTL (dependent variable) with age, sex, SBP, HOMA-IR as independent variables.

<p>Abbreviations: Error SS: error of sum of squares; HOMA-IR, homeostasis model assessment of insulin resistance; LTL, leukocyte telomere length; SBP, systolic blood pressure; S.E.: standard error; <b>Total SS: total sum of squares;</b> Type III SS: type III sum of squares</p><p>Multiple linear regression analysis of LTL (dependent variable) with age, sex, SBP, HOMA-IR as independent variables.</p

Clinical and metabolic characteristics of the study participants in the total group and according to HOMA-IR.

<p><b>Abbreviations:</b> BMI: body mass index; c-f PWV: carotid-femoral pulse wave velocity; DBP: diastolic blood pressure; FG: fasting glucose; HbA_1c: glycosylated hemoglobin; HOMA-IR: homeostasis model assessment of insulin resistance; LTL: leukocyte telomere length; SBP: systolic blood pressure; TA: telomerase activity; 2h OGTT:2-h glucose level following the oral glucose tolerance test; P-value: p between HOMA-IR ≤ 2.5 and HOMA-IR >2.5 groups</p><p>Clinical and metabolic characteristics of the study participants in the total group and according to HOMA-IR.</p

Multiple linear regression analysis of c-f PWV (dependent variable) on age, SBP, LTL, HOMA-IR as independent variables.

<p>Abbreviations: c-f PWV, carotid-femoral pulse wave velocity; Error SS: error of sum of squares; HOMA-IR, homeostasis model assessment of insulin resistance; LTL, leukocyte telomere length; SBP, systolic blood pressure; S.E.: standard error; <b>Total SS: total sum of squares;</b> Type III SS:type III sum of squares.</p><p>Multiple linear regression analysis of c-f PWV (dependent variable) on age, SBP, LTL, HOMA-IR as independent variables.</p

Atorvastatin therapy modulates telomerase activity in patients free of atherosclerotic cardiovascular diseases

Background— Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases. Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now this effect has not been investigated in prospective randomized studies.We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells.Methods—In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35–75 years, free of known cardiovascular diseases and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months. TA was measured by quantitative polymerase chain reaction.Results—At study end 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis. TA expressed as natural logarithms changed from 0.46±0.05 to 0.68±0.06 (p=0.004) in the atorvastatin group and from 0.67±0.06 to 0.60±0.07 (P=0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (p=0.05) of the changes in TA independently of markers of chronic inflammation and oxidative stress. Atorvastatin therapy was associated with increases in IL-6 within the normal range and a tendency towards reductionin blood urea.Conclusions—These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector

Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte Telomere Length as Determinants of Arterial Aging in Subjects Free of Cardiovascular Diseases

Background: Increased arterial stiffness (AS), intima-media thickness (IMT), and the presence of atherosclerotic plaques (PP) have been considered as important aspects of vascular aging. It is well documented that the cardiovascular system is an important target organ for growth hormone (GH) and insulin-like growth factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the risk for cardiovascular diseases (CVD). The telomere length of peripheral blood leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed as an independent predictor of (CVD). The aim of this study is to determine the role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in the vascular aging.Methods: The study group included 303 ambulatory participants free of known CVD (104 males and 199 females) with a mean age of 51.8 ± 13.3 years. All subjects had one or more CVRF [age, smoking, arterial hypertension, obesity, dyslipidemia, fasting hyperglycemia, insulin resistance—HOMA (homeostatic model assessment) &gt;2.5, or high glycated hemoglobin]. The study sample was divided into the two groups according to age as “younger” (m ≤ 45 years, f ≤ 55 years) and “older” (m &gt; 45 years, f &gt; 55 years). IMT and PP were determined by ultrasonography, AS was determined by measuring the carotid-femoral pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL was determined by PCR. Serum IGF-1 and GH concentrations we measured by immunochemiluminescence analysis.Results: Multiple linear regression analysis with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an independent relationship with all the arterial wall parameters investigated in the younger group. In the model with c-f PWV as a dependent variable, p &lt; 0.001 for HOMA, p = 0.03 for GH, and p = 0.004 for LTL. In the model with IMT as a dependent variable, p = 0.0001 for HOMA, p = 0.044 for GH, and p = 0.004 for IGF-1. In the model with the number of plaques as a dependent variable, p = 0.0001 for HOMA, and p = 0.045 for IGF-1. In the older group, there were no independent significant associations between GH/IGF-1, LTL, HOMA, and arterial wall characteristics.Conclusions: GH/IGF-1, IR, HOMA, and LTL were the important parameters of arterial aging in younger healthy participants