Endothelial dysfunction has been reported in obese subjects, but its mechanism has not been elucidated. We have therefore investigated 1) the possible relationship among BMI, waist-to-hip ratio ...(WHR), and endothelium-dependent vasodilation and 2) whether oxidative stress participates in endothelial dysfunction. We recruited 76 healthy subjects (50 men and 26 women aged 21-45 years) and measured their BMI (kg/m2), WHR, and insulin resistance (IR) estimated by the homeostasis model assessment (HOMA). Endothelium-dependent and -independent vasodilation were assessed by increasing doses of acetylcholine (ACh) (7.5, 15, and 30 pg x ml(-1) x min(-1)) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 microg x ml(-1) x min(-1)) during saline and vitamin C coinfusion (24 mg/min). The effects of cyclooxygenase activity were evaluated by a dose-response curve to intrabrachial coinfusion of ACh and indomethacin (500 microg/min). Three different groups have been identified according to their BMI: group A (BMI <25), consisting of 10 men and 5 women; group B (BMI between 25 and 29), consisting of 16 men and 8 women; and group C (BMI > or =30), consisting of 24 men and 13 women. Obese subjects had significantly lower forearm blood flow (FBF) during ACh infusions (means +/- SD): 19.8 +/- 2.8, 10.8 +/- 2.7, and 6.5 +/- 1.8 ml x 100 ml(-1) tissue x min(-1) (P < 0.0001) for groups A, B, and C, respectively. SNP caused comparable increments in FBF in all groups. Regression analysis revealed a significant negative correlation between BMI (r = -0.676, P < 0.0001), WHR (r = -0.631, P < 0.0001), fasting insulin (r = -0.695, P < 0.0001), HOMA-IR (r = -0.633, P < 0.0001), and percent peak increase in FBF during ACh infusion. In obese subjects, both vitamin C and indomethacin increased the impaired vasodilating response to ACh, whereas the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated vasodilation is blunted, and the increase in FBF is inversely related to BMI, WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and indomethacin on impaired ACh-stimulated vasodilation support the hypothesis that oxidative stress contributes to endothelial dysfunction in human obesity.
We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged ...20–46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20–45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 μg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 μg/min) and L-NMMA (2, 4, 8 μmol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 μg/min), FBF was 27.0±3.4 versus 11.5±1.9 ml·100 ml tissue
−1·min
−1 respectively (
P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9±1.5 ml·100 ml tissue
−1·min
−1 (
P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPUK
Objectives. This study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI).
...Background. The renin–angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy.
Methods. The study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient.
Results. Left ventricular mass index values (mean ± SD) were 137 ± 28 g/m2in patients with the DD genotype, 125 ± 27 g/m2in those with the ID genotype and 115 ± 27 g/m2in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio OR 2.497, 95% confidence interval CI interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02).
Conclusions. Our data show that the LVMI was significantly enhanced in patients with the DD genotype.
(J Am Coll Cardiol 1997;29:365–9)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Obesity and Body Fat Distribution Induce Endothelial Dysfunction by
Oxidative Stress
Protective Effect of Vitamin C
Francesco Perticone ,
Roberto Ceravolo ,
Mafalda Candigliota ,
Giorgio Ventura ,
...Saverio Iacopino ,
Flora Sinopoli and
Pier L. Mattioli
From the Cardiovascular Disease Unit, Department of Experimental and
Clinical Medicine G. Salvatore, University of Catanzaro Magna Graecia,
Catanzaro, Italy.
Address correspondence and reprint requests to Francesco Perticone, MD,
Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Policlinico
Mater Domini—Via T. Campanella, 88100 Catanzaro, Italy. E-mail:
perticone{at}unicz.it
.
Abstract
Endothelial dysfunction has been reported in obese subjects, but its
mechanism has not been elucidated. We have therefore investigated 1 )
the possible relationship among BMI, waist-to-hip ratio (WHR), and
endothelium-dependent vasodilation and 2 ) whether oxidative stress
participates in endothelial dysfunction. We recruited 76 healthy subjects (50
men and 26 women aged 21-45 years) and measured their BMI (kg/m 2 ),
WHR, and insulin resistance (IR) estimated by the homeostasis model assessment
(HOMA). Endothelium-dependent and -independent vasodilation were assessed by
increasing doses of acetylcholine (ACh) (7.5, 15, and 30 μg ·
ml -1 · min -1 ) and sodium nitroprusside (SNP)
(0.8, 1.6, and 3.2 μg · ml -1 · min -1 )
during saline and vitamin C coinfusion (24 mg/min). The effects of
cyclooxygenase activity were evaluated by a dose-response curve to
intrabrachial coinfusion of ACh and indomethacin (500 μg/min). Three
different groups have been identified according to their BMI: group A (BMI
<25), consisting of 10 men and 5 women; group B (BMI between 25 and 29),
consisting of 16 men and 8 women; and group C (BMI ≥30), consisting of 24
men and 13 women. Obese subjects had significantly lower forearm blood flow
(FBF) during ACh infusions (means ± SD): 19.8 ± 2.8, 10.8
± 2.7, and 6.5 ± 1.8 ml · 100 ml -1 tissue
· min -1 ( P < 0.0001) for groups A, B, and C,
respectively. SNP caused comparable increments in FBF in all groups.
Regression analysis revealed a significant negative correlation between BMI
( r = -0.676, P < 0.0001), WHR ( r = -0.631,
P < 0.0001), fasting insulin ( r = -0.695, P <
0.0001), HOMA-IR ( r = -0.633, P < 0.0001), and percent
peak increase in FBF during ACh infusion. In obese subjects, both vitamin C
and indomethacin increased the impaired vasodilating response to ACh, whereas
the SNP effect was unchanged. In conclusion, in obese subjects, ACh-stimulated
vasodilation is blunted, and the increase in FBF is inversely related to BMI,
WHR, fasting insulin, and HOMA-IR. The effects of both vitamin C and
indomethacin on impaired ACh-stimulated vasodilation support the hypothesis
that oxidative stress contributes to endothelial dysfunction in human
obesity.
Footnotes
P.L.M. is deceased.
ACh, acetylcholine; ANOVA, analysis of variance, BP, blood pressure; FBF,
forearm blood flow; HOMA, homeostasis model assessment; IR, insulin
resistance; NO, nitric oxide; SNP, sodium nitroprusside; VR, vascular
resistance; WHR, waist-to-hip ratio.
Accepted September 18, 2000.
Received February 15, 2000.
by the American Diabetes Association,
Inc.
To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives.
We enrolled 200 hypertensive outpatients that underwent clinical and ...ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45.
The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different.
The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.
To examine whether middle (two months) and long-term (six months) isradipine sustained-release treatment improves endothelium-dependent vasodilation in never treated hypertensive patients.
The ...responses of the forearm vasculature to acetylcholine (7.5, 15 and 30 micrograms/min) and sodium nitroprusside (0.8, 1.6, 3.2 micrograms/min) were evaluated in 12 normotensive controls (seven men and five women, aged 25 to 49 years), and in 12 hypertensives (eight men and four women, aged 20 to 47 years) at baseline and after two and six months of isradipine sustained-release treatment. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography.
At baseline, the response to acetylcholine was significantly lower in hypertensives vs controls: at the highest dose (30 micrograms/min), forearm blood flow was 28.6 +/- 2.4 ml/100 ml of tissue per min in the controls vs 8.9 +/- 1.0 ml/100 ml of tissue per min in hypertensive (p < 0.0001). Similarly, vascular resistance was significantly (p < 0.0001) higher in hypertensives: 4.8 +/- 0.5 units (controls) vs 15.1 +/- 1.7 units (hypertensives). After isradipine treatment, the forearm blood flow in hypertensive patients changed from 8.9 +/- 1.0 ml/100 ml of tissue per min to 16.0 +/- 1.2 ml/100 ml of tissue per min (two months; p < 0.0001) and 15.2 +/- 1.4 ml/100 ml of tissue per min (six months; p < 0.0001). Isradipine treatment did not modify the vasodilating effect of sodium nitroprusside.
Our data demonstrate for the first time that the calcium antagonist isradipine improves acetylcholine-induced vasodilation in hypertensives.
: Cardiovascular disease (CVD) accounts for more than 17 million deaths per year worldwide. It has been estimated that the influence of lifestyle on CVD mortality amounts to 13.7% for smoking, 13.2% ...for poor diet, and 12% for inactive lifestyle. These results deeply impact both the healthy status of individuals and their skills in working. The impact of CVD on productivity loss accounts for the 24% in total costs for CVD management.Mediterranean diet (MedD) can positively impact on natural history of CVD. It is characterized by a relatively high consumption of inexpensive and genuine food such as cereals, vegetables, legumes, nuts, fish, fresh fruits, and olive oil as the principal source of fat, low meat consumption and low-to-moderate consumption of milk, dairy products, and wine.Its effects on cardiovascular health are related to the significant improvements in arterial stiffness. Peripheral artery disease, coronary artery disease, and chronic heart failure are all positively influenced by the MedD. Furthermore, MedD lowers the risk of sudden cardiac death due to arrhythmias.The present narrative review aims to analyze the effects of MedD on CVD.
Clinical experience and several large studies in the field have found that SARS-CoV-2 infection can cause long-term persistent cardiovascular (CV) impairment beyond the acute phase of the disease. ...This has resulted in a major public health concern worldwide. Regarding COVID-related long-term involvement of various organs and systems, using specific definitions and terminology is crucial to point out time relationships, lingering damage, and outcome, mostly when symptoms and signs of CV disease persist beyond the acute phase. Due to a lack of a common standardized definition, investigators have used interchangeable terms such as "long COVID," "post-COVID," or "post-acute sequelae of COVID-19" to describe CV involvement, thus causing some confusion. For the sake of clarity, the aim of this paper is to discuss the definition and terminology used in defining sequelae after the acute phase of COVID-19, thus pointing out the meaning of definitions like acute cardiac injury, post-acute sequelae of COVID-19, long COVID syndrome, and increased risk of atherosclerotic cardiovascular disease.
Atherosclerotic lesions lie in regions of low wall shear stress. No relationship between wall shear stress and intima-media thickness in vivo has been reported. Aims of the present study were to ...verify the reproducibility of wall shear stress measurement in vivo and to evaluate its association with intima-media thickness in the common carotid artery in healthy subjects.
Wall shear stress was calculated according to the following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal Diameter. Blood viscosity was measured by use of a cone/plate viscometer. Blood velocity, internal diameter, and intima-media thickness were measured by high-resolution echo Doppler. Twenty-one healthy male subjects were investigated. Peak and mean shear stress values were 29.5 +/- 8.2 and 12.1 +/- 3.1 dynes/cm-2 (mean +/- SD), respectively. Peak shear stress was inversely related to intima-media thickness (r = .62), age (r = .77), systolic blood pressure (r = .61), and body mass index (r = .59) (P < .001 for all coefficients). Mean shear stress yielded similar results. The relationship between shear stress and intima-media thickness was independent of age, blood pressure, and body mass index. The reproducibility, calculated by Kendall's W test, was statistically significant.
Our results demonstrate that common carotid artery wall shear stress measurement in vivo is reproducible. It inversely relates to intima-media thickness, age, systolic blood pressure, and body mass index. These findings confirm in vivo the role of shear stress in intima-media thickening.
OBJECTIVES
To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a ...multi-institutional experience.
METHODS
We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates.
RESULTS
Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12, smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis.
CONCLUSIONS
ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.
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