Marina Shargorodsky

Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients.

BACKGROUND & AIMS Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients. The present study was designed to evaluate long term impact of high doses of vitamin D on arterial properties, glucose homeostasis, adiponectin and leptin in patients with type 2 diabetes mellitus. METHODS AND RESULTS In randomized, placebo-controlled study 47 diabetic patients were assigned into two groups: Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months. Group 2 received matching placebo capsules. Blood sampling for metabolic parameters, including fasting glucose, lipid profile, HbA1C, insulin, hs-CRP, 25 OH Vit D, adiponectin and leptin was performed at baseline and at the end of the study. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR). Central aortic augmentation index (AI) was evaluated using SphygmoCor. RESULTS The two groups were similar at baseline in terms of hemodynamic parameters. After 12 months, AI decreased significantly during the treatment period in patients received vitamin D (p < 0.0001) and did not change in placebo group. Glucose homeostasis parameters, leptin as well as leptin adiponectin ratio did not change in both groups. 25 OH Vit D level significantly increased (p = 0.022) and circulating adiponectin marginally increased (p = 0.065) during 12 month treatment period in active treatment and did not change in placebo group. CONCLUSIONS High doses of vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment. This beneficial vascular effect was not associated with improvement in glucose homeostasis parameters.

Treatment with atorvastatin improves small artery compliance in patients with severe hypercholesterolemia.

BACKGROUND We studied the effect of atorvastatin on arterial compliance in patients with severe hypercholesterolemia. METHODS Seventeen patients with low-density lipoprotein cholesterol levels above 170 mg/dL, were included in the study, none of whomever received hypolipidemic medication or had other risk factors. Patients were followed for five visits, every 4 weeks. RESULTS After 20 weeks of treatment, lipid profile improved significantly. Large artery elasticity index did not change significantly, but small artery elasticity index increased by 21% (4.6+/-0.5 to 5.6+/-0.9, P < .01). Although none of our patients suffered from hypertension, both systolic and diastolic blood pressure (BP) decreased significantly (6 mm Hg and 3 mm Hg, respectively). CONCLUSIONS We conclude that atorvastatin improves the elasticity of small arteries and reduces systolic and diastolic BP in patients with severe hypercholesterolemia.

Effect of long-term treatment with antioxidants (vitamin C, vitamin E, coenzyme Q10 and selenium) on arterial compliance, humoral factors and inflammatory markers in patients with multiple cardiovascular risk factors.

BackgroundAntioxidant supplementations have the potential to alleviate the atherosclerotic damage caused by excessive production of reactive oxygen species (ROS). The present study evaluated the effects of prolonged antioxidant treatment on arterial elasticity, inflammatory and metabolic measures in patients with multiple cardiovascular risk factors.MethodsStudy participants were randomly assigned to two groups. Group 1 received oral supplementation with 2 capsules per day of Mid Life Guard, SupHerb, Israel. In each capsule vitamin C (500 mg) vitamin E (200 iu), co-enzyme Q10 (60 mg) and selenium (100 mcg), Group 2 received matching placebo(SupHerb) for 6 months. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, hs-CRP, endothelin, aldosterone, plasma renin activity and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota).ResultsAntioxidant-treated patients exhibited significant increases in large arterial elasticity index (LAEI) as well as small arterial elasticity index (SAEI). A significant decline HbA1C and a significant increase in HDL-cholesterol were also observed. In the placebo group, significant changes in LAEI, SAEI or metabolic measures were not observed.ConclusionsAntioxidant supplementation significantly increased large and small artery elasticity in patients with multiple cardiovascular risk factors. This beneficial vascular effect was associated with an improvement in glucose and lipid metabolism as well as decrease in blood pressure.

Treatment with rosiglitazone reduces hyperinsulinemia and improves arterial elasticity in patients with type 2 diabetes mellitus

OBJECTIVE The aim of this study was to determine whether reduction of hyperinsulinemia with rosiglitazone will improve vascular elasticity in patients with non-insulin dependent diabetes mellitus. METHODS In an open label study 52 patients with non-insulin dependent diabetes mellitus and at least one additional cardiovascular risk factor, were treated for 6 months with 4 mg of rosiglitazone, and uptitrated to 8 mg after 3 months of treatment, if needed. At the beginning of the study and at its end, blood was drawn for insulin, C- peptide, and 24-h urine collected for microalbuminuria/proteinuria. Glucose, chemistry, lipid profile, and hemoglobin A1C were determined at 0, 3, and 6 months. Vascular compliance was measured in monthly intervals. RESULTS Treatment increased significantly small artery elasticity from 1.45 to 2.43 mL/mm Hg x 100. Large artery elasticity tended to increase toward the end of the study (P = not significant). Systolic blood pressure (BP)decreased from 144 to 124 mm Hg and diastolic BP decreased from 80 to 62.5 mm Hg, despite mild weight gain [corrected]. Heart rate tended to decrease from 76.3 to 74.7 beats/min (P = not significant). Systemic vascular resistance decreased from 1789.8 to 1329.4 dyne sec/cm(5). Plasma insulin, in patients not treated with insulin, decreased from 42.45 +/- 24.90 to 27.86 +/- 14.86 IU/mL (P =.0001). CONCLUSIONS Treatment with rosiglitazone reduced hyperinsulinemia and improved small artery elasticity with a tendency to improve large artery elasticity, in hypertensive and in normotensive patients. Because rosiglitazone improves insulin receptor sensitivity (IRS), it is logical to assume that the reduction in hyperinsulinemia reflects improvement in IRS. Our data support the hypothesis that hyperinsulinemia and IRS participate in the mechanisms of tissue injury and their improvement induces improvement in arterial elasticity.

Treatment with amlodipine andatorvastatin have additive effect in improvement of arterial compliance in hypertensive hyperlipidemic patients

BACKGROUND This study investigates the effect of amlodipine on arterial compliance (AC), and the effect of atorvastatin on AC when given in combination with amlodipine. METHODS Twenty-one consecutive hypertensive hyperlipidemic patients were included in this study. Patients were followed every month for 6 months (3 months of amlodipine therapy and 3 months of amlodipine and atorvastatin combination). RESULTS During the 3 months of amlodipine monotherapy, large and small AC were improved by 26% and 38%, respectively, and the systemic vascular resistance was reduced by 10%. The addition of atorvastatin during the next 3 months improved small AC by an additional 42% and decreased the systemic vascular resistance by another 5%, but large AC and blood pressure did not change. CONCLUSIONS Amlodipine improves large and small AC, and the beneficial effect of atorvastatin on small AC is additive to the effect achieved by amlodipine.

Adiponectin and vascular properties in obese patients: is it a novel biomarker of early atherosclerosis?

Objectives:Adiponectin is an adipocyte-derived collagen-like protein, highly specific to adipose tissue and may represent an important link between obesity and atherosclerosis. The present study was designed to investigate a possible association between serum adiponectin levels and early vascular changes in obese patients as determined by intima media thickness (IMT) and arterial pulse-wave contour analysis.Design:Obese subjects (n=47) were evaluated for arterial structure and function, metabolic parameters and serum adiponectin levels.Measurements:IMT was measured by ultrasound. Arterial elasticity was evaluated using pulse-wave contour analysis. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR).Results:Adiponectin was significantly, inversely associated with mean IMT (r=−0.369, P=0.011) and significantly positively associated with large artery elasticity index (LAEI) (r=0.467, P=0.001) as well as small artery elasticity index (SAEI) (r=0.462, P=0.001). In separate multivariate models, adiponectin remained significantly associated with mean IMT, LAEI and SAEI even after adjustment for cardiovascular confounders. Among metabolic parameters, adiponectin was significantly positively associated with HDL cholesterol and inversely associated with triglycerides. Adiponectin was significantly inversely associated with fasting insulin and HOMA-IR. In addition, a marginally inverse association between adiponectin and ALT was observed.Conclusions:In this study, serum adiponectin levels were significantly associated with indices of subclinical atherosclerosis, such as IMT and arterial compliance in obese patients. This association was independent of traditional cardiovascular risk factors.

Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial

Insulin resistance has an important role in the development of nonalcoholic fatty liver disease (NAFLD) and is involved in both pathological processes: hepatic steatosis and atherosclerosis. Therefore, treatment of NAFLD with insulin sensitizers is likely to have a favorable effect toward hepatic steatosis and cardiovascular outcomes. The present study investigated the effect of metformin on arterial properties, metabolic parameters, and liver function in patients with NAFLD. In a randomized, placebo-controlled study, 63 patients with NAFLD were assigned to 1 of 2 groups: Group 1 received daily metformin; group 2 received placebo. Pulse wave velocity (PWV) and augmentation index (AI) were measured using SphygmoCor (version 7.1; AtCor Medical, Sydney, Australia) at baseline and at the end of the 4-month treatment period. Metabolic measures and serum adiponectin levels were determined. Among metformin-treated patients, PWV and AI decreased significantly during the study. Significant declines in fasting glucose, triglyceride, and alkaline phosphatase and a significant increase in high-density lipoprotein cholesterol were observed. Alanine aminotransferase decreased and serum adiponectin increased marginally. In the placebo group, neither PWV nor AI improved significantly during the treatment period. Alanine aminotransferase, aspartate aminotransferase, and adiponectin did not change in the placebo group. Metformin treatment was associated with significant decrease in PWV and AI in NAFLD patients. This beneficial vascular effect was accompanied by an improvement in glucose and lipid metabolism as well as liver enzymes.

The effect of a rapid weight loss induced by laparoscopic adjustable gastric banding on arterial stiffness, metabolic and inflammatory parameters in patients with morbid obesity.

Objective:To determine the effect of drastic weight loss on arterial compliance, inflammatory and metabolic parameters in patients with morbid obesity with and without cardiovascular risk factors who underwent laparoscopic adjustable gastric banding (LAGB).Design:Open prospective study, morbidly obese subjects divided into low- and high-risk group were evaluated before and 4 months after LAGB.Subjects:Forty-one Caucasian subjects aged between 16 and 55 years, with morbid (grade 3) obesity (20 low- risk and 21 high-risk subjects) who underwent LAGB and completed a 16-week follow-up.Measurments:Patients were evaluated at baseline and 4 months after LAGB for body mass index (BMI), arterial blood pressure (BP), metabolic factors including lipid profile, HbA1C, insulin, C-peptide, fibrinogen, hs-C reactive protein (CRP) and Homeostasis model assessment-insulin resistance (HOMA-IR). Arterial elasticity of large and small arteries was evaluated using pulse-wave contour analysis method (HDI CR 2000, Eagan, Minnesota) at baseline and after 4 months.Results:Body mass index reduction induced by LABG, from 43.55±5.11 to 35.10±4.87 in low-risk patients and from 42.90±3.22 to 35.00±3.24 in high-risk patients, significantly improved small artery elasticity (SAE) from 6.30±2.74 to 7.25±1.85, in morbidly obese patients with multiple cardiovascular risk factors (high-risk group). Improvement in SAE was accompanied by improvement of arterial BP, glucose and lipid metabolism, and reduction of CRP values.Conclusion:Although dramatic weight reduction induced by surgical intervention was associated with similar changes in body weight and significant improvement of metabolic and inflammatory parameters in two groups of obese patients, SAE improved only in high-risk patients.

Weight loss induced by nutritional and exercise intervention decreases arterial stiffness in obese subjects.

BACKGROUND & AIMS Obesity is associated with increased arterial stiffness, an early marker of vascular wall damage. However, data on the long-term vascular impact of intentional weight loss are limited. The aim of the present study was to evaluate the effect of weight loss induced by nutritional and exercise intervention on arterial compliance, metabolic and inflammatory parameters in obese patients who participated in a weight reduction program. METHODS In an open label, prospective study, 37 obese subjects attended a 24 weeks nutritional and exercise interventional program. Arterial elasticity was evaluated using pulse-wave contour analysis (HDI CR-2000, Eagan, Minnesota) at baseline and at the end of the study. Fasting glucose, HbA1C, insulin, lipid profile, hs-CRP, fibrinogen were measured at baseline and after 6 months. Insulin resistance was assessed by homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS BMI decreased from 36.1 +/- 7.4 kg/m(2) at baseline to 32.8 +/- 7.4 kg/m(2) after 6 months (p<0.0001). Large artery elasticity index (LAEI) increased from 12.1 +/- 4.1 to 15.8 +/- 4.7 ml/mmHg x 10 during the study (p<0.0001). Small artery elasticity index (SAEI) increased from 4.4+/-2.4 to 5.5 +/- 2.7 ml/mmHg x 100 (p<0.0001). There was a significant improvement in fasting hyperglycemia, HbA1C and significant decrease in LDL-cholesterol, fibrinogen and C-reactive protein. Modest reduction in HOMA-IR was observed. The change in weight was positively associated with LAEI, SAEI, total cholesterol, insulin and HOMA-IR. CONCLUSIONS Moderate weight loss induced by nutritional and exercise intervention improved small and large artery elasticity. The increase in arterial elasticity was associated with improvement in glucose and lipids homeostasis as well as markers of inflammation.

Prolonged treatment with the at1 receptor blocker, valsartan, increases small and large artery compliance in uncomplicated essential hypertension

BACKGROUND Decreased arterial compliance (AC) is considered an early marker of vascular wall damage. Hypertension gradually decreases arterial compliance. We studied whether treatment with the angiotensin type 1 (AT(1)) antagonist valsartan will affect AC in patients with essential hypertension (EH). METHODS Twenty-two patients with EH, 6 men and 16 women, mean age 58.7 +/- 4.1 years, without overt target organ damage were included. Antihypertensive medications were withdrawn for 3 weeks, Valsartan was given at 80- and 160-mg doses. The AC, blood pressure (BP), blood, and urine were measured monthly. Large (C1) and small (C2) AC were derived from radial artery waveforms, obtained using a calibrated tonometer (model CR-2000, HDI Inc., Eagan, MN). RESULTS After 3 months, systolic BP decreased from 172 +/- 17 to 142 +/- 13 mm Hg (P <.0001) and diastolic BP from 95 +/- 9 to 82 +/- 8 mm Hg (P <.0001). The decrease in BP was significant within 1 month and improved further on. The C1 increased by 22%, from 8.0 +/- 3.1 to 9.7 +/- 2.3 mL/mm Hg x 10 (P <.01). The C2 increased by 35%, from 2.9 +/- 1.3 to 3.9 +/- 1.9 mL/mm Hg x 100 (P <.01). Both C1 and C2 reached statistical significance only after 3 months. Systemic vascular resistance (SVR) decreased by 15% from 2,140 +/- 376 to 1,817 +/- 262 dynes/sec/cm(-5) (P <.0001). CONCLUSIONS Treatment with valsartan in patients with EH improves small and large AC. The improvement in AC was significant only after 3 months of treatment, whereas systolic BP, diastolic BP, and SVR decreased earlier. The AT(1) receptor blockade with valsartan seems to be an effective means of not only lowering BP but of reversal of vascular wall damage, which predisposes to cardiovascular events.