[Show abstract][Hide abstract] ABSTRACT: Background. Teriparatide is a potent anabolic agent for severe osteoporosis. Objectives. A primary objective of this retrospective study was to define the efficacy of teriparatide in terms of bone mineral density (BMD) changes and relief of back pain in clinical practice. Methods. The patient population comprises 119 osteoporotic patients treated with teriparatide for median 539 (range 179-926) days. Results. The mean BMD gain was 0.9% in the total hip (P = 0.0075), 2.1% in the femoral neck (P = 0.0006), and 8.5% in the lumbar spine (P = 0.0085). In the whole patient population age associated inversely with BMD changes in the total hip (P = 0.019) and in the femoral neck (P = 0.0036). A history of significant bisphosphonate pretreatment (n = 90) reduced BMD response in the total hip (P = 0.039). The total exposure of any prior bisphosphonate was negatively correlated with BMD response in the total hip (P = 0.0421). Half of the patients reported relief of back pain during the treatment. Leg pain, nausea, and dizziness were most frequent adverse concerns. Conclusions. Teriparatide works in clinical practice as well as in clinical trials. Younger subjects benefited more than older patients from teriparatide in the total hip and in the femoral neck. Bisphosphonate pretreatment attenuated teriparatide-induced BMD gain.
[Show abstract][Hide abstract] ABSTRACT: Impaired adipose tissue (AT) blood flow has been implicated in the pathogenesis of insulin resistance in obesity. Insulin and bradykinin are meal-stimulated promoters of AT blood flow and glucose metabolism.
We tested whether blood flow regulates glucose metabolism in AT, insulin and bradykinin exert additive effects on AT blood flow and metabolism, and any of these actions explains the insulin resistance observed in obese individuals.
Perfusion and glucose metabolism in the AT of the thighs were studied by positron emission tomography and H(2)(15)O (flow tracer) and (18)F-2-fluoro-2-deoxyglucose. Study I included five subjects in whom positron emission tomography imaging was performed in the fasting state during intraarterial infusion of bradykinin in the left leg; the right leg served as a control. Study II included seven lean and eight obese subjects in whom the imaging protocol was performed during euglycemic hyperinsulinemia.
Bradykinin alone doubled fasting AT blood flow without modifying glucose uptake. Hyperinsulinemia increased AT blood flow (P ≤ 0.05) similarly in lean and obese individuals. In the lean group, bradykinin increased insulin-mediated AT glucose uptake from 8.6 ± 1.6 to 12.3 ± 2.4 μmol/min · kg (P = 0.038). In the obese group, AT glucose uptake was impaired (5.0 ± 1.0 μmol/min · kg, P = 0.05 vs. the lean group), and bradykinin did not exert any metabolic action (6.0 ± 0.8 μmol/min · kg, P = 0.01 vs. the lean group).
AT blood flow is not an independent regulator of AT glucose metabolism. Insulin is a potent stimulator of AT blood flow, and bradykinin potentiates the hemodynamic and metabolic actions of insulin in lean but not in obese individuals.
The Journal of clinical endocrinology and metabolism 04/2012; 97(7):E1192-6. · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/Aims. Natriuretic peptides are associated with the cardiovascular disease risk under a range of different circumstances. However, less is known about whether this association is found also in young healthy subjects. Methods. 9 patients with dilated cardiomyopathy and 26 healthy young subjects were studied. The myocardial blood flow measurements were performed basally and during adenosine infusion using PET. Results. S-proBNP concentrations were significantly higher (2153 ± 1964 versus 28 ± 17 ng/L, P = .000002) and adenosine-stimulated flow lower (1.6 ± 0.8 versus 3.6 ± 1.1 mL·g(-1)·min(-1), P = .00001) in patients with dilated cardiomyopathy when compared to healthy subjects. S-proBNP concentration was inversely associated with adenosine stimulated flow in patients with dilated cardiomyopathy (r = -0.75, P = .019) but not in healthy subjects (r = -0.06, P = .84). Conclusions. Natriuretic peptides are inversely associated with coronary vasoreactivity in patients with dilated cardiomyopathy but not in healthy young subjects. Since reduced coronary vasoreactivity seems to be one of the earliest abnormalities in the development of coronary artery disease, this might indicate that natriuretic peptides are not predictor of cardiovascular disease risk in healthy young subjects.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to examine whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene affects the vasodilatory properties of coronary arteries in healthy men. The ACE genotypes of 128 men (mean age 35 +/- 4 years) were determined and related to myocardial blood flow. The blood flow was measured by positron emission tomography at rest and during vasodilation caused by adenosine or dipyridamole infusion. The coronary flows and resistances at rest and during stimulation with adenosine or dipyridamole did not differ between the ACE genotypes. Furthermore, this polymorphism had no effect on coronary flow reserve corrected by a rate-pressure product. In conclusion, the ACE I/D polymorphism does not seem to affect myocardial reactivity--an early indicator of atherosclerosis--in healthy subjects.
Scandinavian Journal of Clinical and Laboratory Investigation 02/2007; 67(6):596-603. · 1.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The hepatic lipase (HL) gene C-480T promoter polymorphism affects gene transcription and enzyme activity and leads to CC, CT, and TT genotypes. Recently, HL expression was detected in macrophages. It has been postulated that HL might have a direct role in the pathogenesis of atherosclerosis without changes in the plasma profile. We hypothesized that the difference of plasma cholesterol level may not influence the effect of HL genotype on coronary reactivity.
A total of 108 young men (aged 34+/-5 years) were genotyped and divided into three groups. These groups contained 45, 49 and 14 men having either normal (4.9+/-1.2 mmol/L), mildly (5.5+/-0.8 mmol/L) or severely (7.8+/-1.9 mmol/L, subjects with familial hypercholesterolemia) elevated mean plasma cholesterol level, respectively. Myocardial blood flow (MBF) was measured at rest and during adenosine or dipyridamole-induced hyperemia with positron emission tomography using [(15)O] H(2)O.
The effect of HL genotype on the indices of MBF was parallel within all cholesterol groups and therefore they were combined. In all subjects, basal flow did not differ between the genotypes. However, men with CC genotype had a significantly higher hyperemic blood flow (3.86+/-1.26 mLg(-1)min(-1) versus 3.20+/-1.38 mLg(-1)min(-1), p=0.007), higher coronary flow reserve (CFR, 4.80+/-1.77 versus 3.77+/-1.43, p=0.001) and lower coronary resistance during hyperemia (25.63+/-9.98 mmHg min g mL(-1) versus 35.00+/-23.95 mmHg min g mL(-1), p=0.003) than T allele carriers. In multivariate regression analysis, after adjustment for age, body mass index, serum lipids, blood pressure, adenosine or dipyridamole administration, and study group, HL polymorphism was an independent predictor of blood flow during hyperemia (p=0.016), coronary resistance (p=0.014), and CFR (p=0.005), respectively.
The HL C-480 T polymorphism is associated with CFR, which is an early indicator of atherosclerosis, independently of the level of plasma cholesterol in young men.
[Show abstract][Hide abstract] ABSTRACT: Positive family history as a risk factor for coronary artery disease seems to be most important in subjects who otherwise are at low risk. We examined the association between family history of coronary artery disease and myocardial vasoreactivity in healthy men.
35 non-smoking healthy men (age 35+/-7 years) were studied: 16 had positive family history of coronary artery disease and 19 had negative family history. The myocardial blood flow measurements were performed basally and during adenosine infusion (140 mug/kg/min) with and without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and O-15-water.
Basal myocardial blood flow was similar between the subjects with positive and negative family history of coronary artery disease (0.79+/-0.19 and 0.79+/-0.21 mL g(-1) min(-1), NS). Adenosine stimulated flow was significantly reduced in subjects with positive family history (3.0+/-0.5 vs 4.0+/-1.2 mL g(-1) min(-1), respectively, p=0.003). During physiological hyperinsulinemia adenosine stimulated flow was further enhanced in both groups but significantly blunted in subjects with positive family history (3.7+/-0.9 vs 5.2+/-1.5 mL g(-1) min(-1), respectively, p=0.001). These differences remained significant after simultaneous controlling for age, BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure (p=0.002).
Healthy non-smoking men with positive family history of coronary artery disease are characterized by impaired myocardial vasoreactivity.
International journal of cardiology 11/2006; 112(3):289-94. · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obese subjects are characterized by increased high-sensitivity C-reactive protein (hsCRP) and coronary vascular resistance. Clucocorticoids suppress inflammation, a possible cardioprotective effect. We tested the short-term anti-inflammatory effect of dexamethasone (dx) on these parameters in obese subjects.
Coronary vascular resistance was quantitated basally and during adenosine infusion with or without simultaneous euglycemic hyperinsulinemic clamp (insulin infusion rate of 1 mU/kg/min) in 11 obese and 19 age-matched nonobese males using positron emission tomography and (15)O-water. Each subject was studied both with and without previous dx treatment for 2 days (2 mg/day).
Before dx treatment, hsCRP concentration was significantly higher in obese than in nonobese subjects (1.55+/-1.73 vs 0.32+/-0.32 mg/l, P = 0.005). In addition, coronary vascular resistances were higher (P < 0.05) in obese than in nonobese subjects at baseline (139+/-36 vs 117+/-22) and during adenosine infusion without (32+/-7 vs 26+/-7) or with simultaneous clamp (26+/-8 vs 21+/-5 mmHg min g/ ml). Dx treatment decreased significantly hsCRP concentration in obese but not in nonobese subjects, leading to similar hsCRP concentrations between the groups (0.45+/-0.43 vs 0.26+/-0.42 mg/l, respectively, P = 0.3). Dx had no effect on coronary vascular resistances (NS).
Obese subjects are characterized by high hsCRP, which can be normalized by dx. However, despite this, coronary vascular resistances did not decrease in obese subjects. Short-term changes in inflammatory response protein appear not to parallel with changes in coronary vasoreactivity in obese men.
International Journal of Obesity 04/2006; 30(3):460-7. · 5.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased mortality in acromegaly has been confined to those with posttreatment basal GH of 2.5 microg/liter or greater, but the impact of IGF-I and pituitary radiotherapy on mortality has remained controversial.
The purpose of this nationwide survey was to examine the all-cause mortality of patients with acromegaly and evaluate the impact of treatment outcome and mode of treatment on survival.
All-cause mortality of all patients with acromegaly diagnosed during January 1980 and December 1999 in the five university hospitals of Finland was followed up by the end of 2002 (12.5 +/- 5.6 yr) and compared with that of the general population by using age- and gender-adjusted standardized mortality ratios (SMRs). Logistic regression analysis was used to investigate factors related to mortality within the survey population.
Mortality was the main outcome measure.
Of the 334 patients, 56 (16.8%) had died during follow-up. SMR of the patients was 1.16 [confidence interval (CI) 0.85-1.54, not significant (NS)]. However, patients with basal serum GH concentration 2.5 microg/liter or greater (SMR 1.63, CI 1.10-2.35, P < 0.001) measured 5.2 +/- 4.4 yr after the initial treatment, and those irradiated (SMR 1.69, CI 1.05-2.58, P < 0.001) showed excess mortality. In a multivariate model, the effect of radiotherapy was of borderline significance only (P = 0.083). Posttreatment IGF-I levels, available for 72.2% of the patients, did not have impact on mortality.
The posttreatment basal GH concentration less than 2.5 microg/liter in acromegalic patients is associated with a normal lifespan. Excess mortality is confined to poorly controlled patients and possibly those who have received conventional radiotherapy.
[Show abstract][Hide abstract] ABSTRACT: We examined the association between lipoprotein(a) and myocardial vasoreactivity in healthy men.
Thirty non-smoking healthy men (age 34+/-6 years) were studied: 9 had increased lipoprotein(a) (>200 mg/L) concentrations (lipoprotein(a) 317 (range 218-550) mg/L) and 21 had normal lipoprotein(a) (<200 mg/L) concentrations (lipoprotein(a) 57 (range 13-156) mg/L). The myocardial blood flow measurements were performed basally and during adenosine infusion (140 microg/kg/min) with or without simultaneous physiological hyperinsulinemia (insulin infusion at a rate of 1 mU/kg/min) using positron emission tomography and [(15)O]H(2)O.
Basal myocardial blood flow was similar between the subjects with increased and normal lipoprotein(a) (0.76+/-0.20 and 0.79+/-0.20 mLg(-1) min(-1), NS). Adenosine-stimulated flow tended to be reduced in subjects with increased lipoprotein(a) (3.1+/-0.7 mLg(-1) min(-1) versus 3.7+/-1.1 mLg(-1) min(-1), respectively, p=0.1). During physiological hyperinsulinemia adenosine-stimulated flow was further enhanced in both groups but significantly blunted in subjects with increased lipoprotein(a) (3.7+/-0.8 mLg(-1) min(-1) versus 4.8+/-1.4 mLg(-1) min(-1), respectively, p=0.03). This difference remained significant after simultaneous controlling for BMI, HbA1c, LDL-cholesterol, HDL-cholesterol and blood pressure (p=0.04).
Already young healthy men with lipoprotein(a) concentrations greater than 200mg/L are characterized by impaired myocardial vasoreactivity.
[Show abstract][Hide abstract] ABSTRACT: Subjects with Type 1 diabetes have impaired coronary vasoreactivity but the independent role of glycaemic control on myocardial perfusion is less clear. We examined the effect of lifetime glycaemic exposure on coronary vasoreactivity in 43 otherwise healthy Type 1 diabetic subjects.
Myocardial blood flow was calculated basally and during pharmacologically induced hyperaemia in the fasting state and during euglycaemic hyperinsulinaemic clamp (at an insulin infusion rate of 1 mU/kg per min for 60 min) using positron emission tomography and (15)O-water. Glycaemic exposure was estimated as glycosylated haemoglobin A(1c) (HbA(1c)) months.
Hyperaemic myocardial blood flow was inversely associated with log HbA(1c) months in the fasting state (r = -0.72, P < 0.01) and during clamp (r = -0.35, P < 0.05). These correlations remained significant after adjustment for lipid values, blood pressures, sex, smoking, body mass index (BMI) and age (r = -0.70, P < 0.05 and r = -0.35, P < 0.05, respectively). No significant correlation was detected between hyperaemic flow and HbA(1c) or plasma glucose values measured immediately preceding the PET study.
The present study demonstrates that the lifetime glycaemic exposure appears to be a better predictor of reduced coronary vasoreactivity than recent glycaemic control in Type 1 diabetic subjects. Reduced coronary vasoreactivity in diabetic subjects with poor glycaemic control and/or long duration of diabetes may represent an early precursor of coronary artery disease.
Diabetic Medicine 02/2005; 22(1):45-51. · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated high-sensitivity C-reactive protein (hsCRP) concentrations indicate increased risk of future coronary events. The association between hsCRP and coronary vasoreactivity has not yet been examined in type 1 diabetic subjects.
We studied 18 young men who were non-smokers and who had uncomplicated type 1 diabetes. The diabetic subjects were divided into two groups, according to their median hsCRP concentration, as follows: (i) subjects with slightly elevated hsCRP (median 0.76 mg/l, range 0.47-4.73 mg/l, n=8); and (ii) subjects with low hsCRP (median 0.32 mg/l, range 0.11-0.35 mg/l, n=10). In addition we investigated 22 non-diabetic age-matched subjects (hsCRP: median 0.42 mg/l, range 0.11-1.31 mg/l). Resting myocardial blood flow and hyperaemic adenosine-stimulated flow during euglycaemic-hyperinsulinaemic clamp were determined using positron emission tomography and oxygen-(15)-labelled water.
Diabetic subjects with slightly elevated hsCRP had significantly higher hsCRP concentrations than non-diabetic subjects (p=0.008). Resting myocardial blood flow was similar (NS) in diabetic subjects with slightly elevated hsCRP (0.79+/-0.19 ml.g(-1).min(-1)) or low hsCRP (0.81+/-0.15 ml.g(-1).min(-1)) and non-diabetic subjects (0.80+/-0.19 ml.g(-1).min(-1)). Adenosine infusion induced a significant increase in blood flow in all study subjects (p<0.001) but was blunted in diabetic subjects with slightly elevated hsCRP (3.42+/-0.61 ml.g(-1).min(-1)) when compared with diabetic subjects with low hsCRP (5.08+/-1.65 ml.g(-1).min(-1), p=0.02) or non-diabetic subjects (4.51+/-1.36 ml.g(-1).min(-1), p=0.04). Adenosine-stimulated flow was inversely correlated with hsCRP concentrations in all diabetic subjects (r=-0.70, p=0.001).
In young subjects with uncomplicated type 1 diabetes, even slightly elevated hsCRP concentrations are associated with reduced coronary vasoreactivity.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effects of acute prolonged exercise (marathon running) on cardiac function and myocardial perfusion. Cardiac dimensions and function were measured in seven endurance-trained men using echocardiography before and repeatedly after marathon (42.2 km) running (at 10 min, 150 min, and 20 h). Myocardial perfusion and perfusion resistance were measured using positron emission tomography and 15O-H2O before and 85-115 min after running. Echocardiographic indices showed only mild and clinically non-significant changes in cardiac function after running. Rate-pressure-corrected basal myocardial perfusion (0.89+/-0.13 vs. 1.20+/-0.32 mL min(-1) g(-1), P=0.04) was increased after running. Also, adenosine-stimulated perfusion tended to be higher (3.67+/-0.81 vs. 4.47+/-0.52 mL min(-1) g(-1), P=0.12) and perfusion resistance during adenosine stimulation was significantly lower after running (26+/-6 vs. 18+/-3 mmHg min g mL(-1), P=0.03). Plasma free fatty acid (FFA) concentration was significantly increased after running. These results show that marathon running does not cause marked changes in cardiac function in healthy men. Basal perfusion was increased after exercise, probably reflecting changes in fuel preferences to increased use of FFAs. Strenuous exercise also seems to enhance coronary reactivity, which could thereby serve as a protective mechanism to vascular events after exercise.
Scandinavian Journal of Medicine and Science in Sports 09/2004; 14(4):208-14. · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the role of the sympathetic nervous system in regulating insulin's action on coronary perfusion in uncomplicated type 1 diabetes by blocking centrally mediated sympathetic activity with dexamethasone.
Positron emission tomography and oxygen 15 labelled water were used to quantify myocardial blood flow basally and during adenosine infusion with or without simultaneous euglycaemic physiological hyperinsulinaemia in nine non-smoking men with type 1 diabetes and 12 healthy non-diabetic men. Each patient was studied both with and without previous dexamethasone treatment for two days (2 mg/day).
Insulin increased coronary flow reserve in diabetic (from 4.3 (0.7) to 5.1 (0.6), p < 0.05) and non-diabetic (from 4.3 (0.3) to 5.4 (0.4), p < 0.05) patients. In contrast to non-diabetic patients dexamethasone pretreatment abolished the insulin induced increase in coronary flow reserve in diabetic patients (p < 0.05) leading to lower coronary flow reserve in diabetic than in non-diabetic patients (3.9 (0.6) v 7.1 (0.9), p < 0.05).
These results show that insulin's ability to modulate coronary perfusion is sustained in young patients with type 1 diabetes without microvascular complications or autonomic neuropathy. Dexamethasone treatment abolished the insulin induced increase in coronary flow reserve in diabetic patients but not in healthy study participants, suggesting that sympathetic activation plays an important part in regulating insulin's effects on myocardial perfusion in patients with type 1 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Insulin resistance in obese subjects results in the impaired use of glucose by insulin-sensitive tissues, e.g., skeletal muscle. In the present study, we determined whether insulin resistance in obesity is associated with an impaired ability of exercise to stimulate muscle blood flow, oxygen delivery, or glucose uptake.
Nine obese (body mass index = 36 +/- 2 kg/m(2)) and 11 age-matched nonobese men (body mass index = 22 +/- 1 kg/m(2)) performed one-legged isometric exercise during hyperinsulinemia. Rates of femoral muscle blood flow, oxygen consumption, and glucose uptake were measured simultaneously in both legs using [(15)O]H(2)O, [(15)O]O(2), [(18)F]fluoro-deoxy-glucose, and positron emission tomography.
The obese subjects exhibited resistance to insulin stimulation of glucose uptake in resting muscle, regardless of whether glucose uptake was expressed per kilogram of femoral muscle mass (p = 0.001) or per the total mass of quadriceps femoris muscle. At similar workloads, oxygen consumption, blood flow, and glucose uptake were lower in the obese than the nonobese subjects when expressed per kilogram of muscle, but similar when expressed per quadriceps femoris muscle mass.
We conclude that obesity is characterized by insulin resistance of glucose uptake in resting skeletal muscle regardless of how glucose uptake is expressed. When compared with nonobese individuals at similar absolute workloads and under identical hyperinsulinemic conditions, the ability of exercise to increase muscle oxygen uptake, blood flow, and glucose uptake per muscle mass is blunted in obese insulin-resistant subjects. However, these defects are compensated for by an increase in muscle mass.
Obesity research 03/2003; 11(2):257-65. · 4.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin resistance in the heart is not localized to the myocardium, but may also occur in blood vessels. We studied the effects of insulin on coronary vasodilation in hypertension. Coronary vascular resistance was quantitated in 11 nonsmoking men with untreated mild essential hypertension and 9 healthy normotensive men using positron emission tomography and (15)O-labeled water. The measurements were performed at baseline and during adenosine infusion (140 microg x kg(-1) x min(-1)) with or without simultaneous euglycemic physiological (serum insulin approximately 70 mU/l) and supraphysiological (serum insulin approximately 460 mU/l) hyperinsulinemia. Coronary resistance was significantly higher in hypertensive than normotensive subjects at baseline and during adenosine infusion. Physiological hyperinsulinemia decreased hyperemic coronary resistance significantly in both groups. Supraphysiological hyperinsulinemia further decreased the hyperemic coronary resistance in normotensive but not in hypertensive subjects, leading to higher hyperemic coronary resistance in hypertensive than normotensive subjects (27.2 +/- 8.7 vs. 19.2 +/- 4.9 mm Hg x min x g x ml(-1), p < 0.05). However, insulin-stimulated whole body glucose uptake values were similar between the groups during both insulin infusions. In conclusion, insulin-induced coronary vasodilation is blunted in young subjects with mild essential hypertension who are otherwise healthy. Coronary vascular resistance to insulin occurs although no change in peripheral glucose uptake can be detected. While we do not know whether the same results can be extrapolated to female or older subjects, these results indicate a novel defect in the regulation of coronary arteries in the early phase of hypertension.
Journal of Vascular Research 01/2003; 40(1):58-67. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The goal of this study was to examine the relationship between plasma asymmetric dimethylarginine (ADMA) level and hyperemic myocardial blood flow (MBF) in subjects with borderline hypertension (BHT) and familial hypercholesterolemia (FH).
Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase that may modulate vascular function. We measured plasma ADMA levels and myocardial flow in 77 young men (mean age 35 +/- 5 years), including 47 healthy controls, 16 men with BHT, and 14 men with FH. Basal and dipyridamole-induced myocardial flow was measured using positron emission tomography. Plasma ADMA levels were measured using high-pressure liquid chromatography.
Asymmetric dimethylarginine levels were significantly elevated in the BHT group compared with controls (0.59 +/- 0.13 micromol/l vs. 0.43 +/- 0.12 micromol/l, p < 0.001), and they had significantly lower dipyridamole flow (2.85 +/- 1.20 ml/min/g vs. 3.69 +/- 1.68 ml/min/g, p < 0.05). In a multivariate regression model adjusted for the study group, dipyridamole flow was inversely associated with ADMA (p < 0.05), age (p < 0.05), and apolipoprotein B concentration (p < 0.05).
We conclude that plasma ADMA concentration is related to dipyridamole-induced vasodilatory function in young men, independently of blood pressure elevation and hypercholesterolemia. Subjects with BHT have significantly increased plasma ADMA levels, which may partly explain the impaired hyperemic MBF in this condition.
Journal of the American College of Cardiology 10/2002; 40(7):1241-7. · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity is associated with increased risk for cardiovascular diseases and peripheral endothelial dysfunction. We examined whether myocardial vasoreactivity and coronary-flow response to insulin stimulation are altered in obesity.
Myocardial blood flow was quantitated in 10 obese men (body mass index, 33.6 +/- 1.9 kg/m(2)) and 10 healthy matched non-obese men (body mass index, 24.2 +/- 1.9 kg/m(2)), using positron emission tomography and oxygen-15-labeled water. The measurements were performed basally and during adenosine infusion (140 microg/kg per minute), with or without simultaneous physiological (1 mU/kg per minute) and supraphysiological (5 mU/kg per minute) hyperinsulinemia.
Basal myocardial blood flow was not significantly different between obese and non-obese subjects. Adenosine-stimulated flow was blunted in obese (3.2 +/- 0.6 mL/g per minute) when compared with non-obese subjects (4.0 +/- 1.1 mL/g per minute, p < 0.05). Simultaneous physiological hyperinsulinemia increased adenosine-stimulated myocardial flow significantly in both groups (to 4.03 +/- 1.24 and 4.85 +/- 1.04 mL/g per minute in obese and non-obese men, respectively; p < 0.05 vs. adenosine). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow in non-obese subjects (to 5.56 +/- 0.98 mL/g per minute; p < 0.05) but not in obese subjects.
Young obese, healthy men have reduced myocardial vasoreactivity, which may represent an early precursor of future coronary artery disease. Additionally, insulin-induced enhancement of myocardial blood flow is blunted in obesity. Thus, endothelial dysfunction seems to also characterize myocardial vasculature of obese subjects.
Obesity research 07/2002; 10(7):617-24. · 4.95 Impact Factor