Baroreflex sensitivity normalization after cardiac resynchronization therapy

To evaluate the relation between peripheral vascular endothelial function and coronary flow reserve (CFR), we assessed flow mediated dilation (FMD) of brachial artery and the intima-media thickness (IMT) of the carotid artery in 32 subjects (mean age 58+/-9 years, M/F=9:23 ) with chest pain and normal coronary angiogram. The subjects were divided into 2 groups according to CFR >or=2.1 or <2.1 measured with transthoracic echocardiography in distal left anterior descending coronary artery. We found % FMD was decreased in the group with CFR <2.1 than those of CFR >or=2.1 and CFR was correlated with peripheral FMD. However, IMT was not different between two groups. These results suggest that microvascular dysfunction is primarily related to endothelial dysfunction rather than advanced atherosclerosis and because it is a generalized process that involves the whole arteries, the measurement of brachial FMD can be a useful diagnostic tool to evaluate microvascular dysfunction in patients with chest pain and normal coronary angiogram.     

Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. METHODS: 40 patients with OSA showing an apnea-hypopnea index (AHI) > or =5 (mean age 51.3 +/- 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 +/- 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. RESULTS: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 +/- 1.88 vs. 6.42 +/- 1.56, respectively) and IMT (0.85 +/- 0.13 vs. 0.63 +/- 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 +/- 1.33 vs. 11.8 +/- 3.36 cm(2)/dyn/10(6)) and FMD (4.57 +/- 1.3 vs. 6.34 +/- 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. CONCLUSION: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.     

Studies on flow-mediated vasodilation and intima-media thickness of the brachial artery in patients with primary hyperparathyroidism

The endothelium is a newly recognized target organ of parathyroid hormone (PTH) and may contribute to its effects on vascular tone and blood pressure regulation. Flow-mediated vasodilation (FMD), brachial and carotid intima-media thickness (IMT) were studied in patients with primary hyperparathyroidism (pHPT) and controls to evaluate endothelial function and structural arterial vessel wall alterations. Sixteen patients with pHPT (mean +/- SEM, age 44 +/- 5 years; PTH 229 +/- 72 ng/L; serum calcium 3.0 +/- 0.06 mmol/L; serum phosphate 2.0 +/- 0.2 mg/L) and 16 normocalcemic control subjects matched for age, sex, and blood pressure were included. Diabetes, hypertension, and vascular disease were excluded in both groups. End-diastolic diameter, flow-mediated (FMD) and nitroglycerin-mediated (NMD) dilation of the brachial artery were measured by a multigate pulsed Doppler system (echo-tracking). IMT was determined using automatic analysis of the M-line signal. Endothelium-dependent FMD was impaired in patients compared to controls (4.6 +/- 1.6% v 19.2 +/- 3.9%, P < .001). NMD (23.8 +/- 3.1% v. 22.4 +/- 2.8%, P = NS), carotid and brachial IMT (0.60 +/- 0.04 mm v 0.64 +/- 0.06 mm, P = NS, and 0.46 +/- 0.04 mm v 0.47 +/- 0.08 mm, P = NS, respectively) and artery diameters were not different. Endothelium-dependent vasodilation is impaired in patients with primary hyperparathyroidism despite normal IMT. Endothelial dysfunction may contribute to increased cardiovascular morbidity and mortality in pHPT.     

Smoking is associated with dose-related increase of intima-media thickness and endothelial dysfunction

Cigarette smoking is firmly established as a risk factor for atherosclerosis. However, the exact mechanism causing smoking-related damage to the arterial wall and its relation to the atherosclerotic process is not known. Also unknown is the time delay between the start of smoking and the sequence of functional and morphologic changes occurring in the arterial wall caused by smoking and their interrelationship. Therefore, the aim of this study was to evaluate the acute and chronic effects of smoking on endothelium-dependent (flow-mediated) dilation (FMD) of the peripheral arteries, the effects of dose and duration of chronic smoking on intima-media thickness (IMT) of the carotid arteries, and their interrelationship. The study encompassed two groups of smokers. In group A there were 40 subjects of both sexes, who smoked on average 17.6 +/- 6.5 cigarettes per day, for 5 to 15 years (mean 8.95 +/- 4.0 years), mean age 28.1 years. Group B consisted of 42 smokers of both sexes who smoked 21.15 +/- 8.2 cigarettes/day for more than 15 years (mean 21.15 +/- 3.4 years), mean age 39.5 years. The control group consisted of 40 healthy subjects without major risk factors of atherosclerosis, mean age 29.1 years. By means of high-resolution ultrasound the brachial artery diameter was measured at rest and during reactive hyperemia (after release of a forearm tourniquet) and the flow-mediated, endothelium-dependent dilation was calculated. The IMT of the carotid arteries was determined in all subjects by use of B-mode ultrasonography. Resting blood flow in the brachial arteries was significantly less in the smokers' groups than in controls (78.8 +/- 31.9 vs 134.9 +/- 45.0 mL/min, p<0.0001). This decrease was much more evident in female than in male smokers. Female smokers also had significantly smaller brachial artery diameter at rest. In smokers the FMD of the brachial artery was reduced (11 +/- 4% vs 7 +/- 4%, p<0.004) and the mean IMT was significantly greater than in controls (0.68 +/- 0.13 vs 0.59 +/- 0.04 mm, p<0.001). Impairments of FMD and IMT increase were related to the duration and to the number of cigarettes smoked. In all subjects IMT was significantly correlated with total and LDL cholesterol, fibrinogen, lipoprotein(a) concentration, body mass index, and age of the subjects, but multivariate analysis showed that only total dose smoked and fibrinogen concentration were independently related to IMT. The results of this study show that smoking is associated with dose-related impairment of FMD and increased IMT of the carotid arteries. Impairment of FMD occurs in smokers very early and is the earliest detectable event, preceding morphologic changes of the vessel wall. Some harmful effects of smoking on the vessel wall are gender related.     

Endothelial dysfunction predictor of structural changes of arterial wall in type I diabetes.

AIM: We examined whether alteration in vascular endothelial function exists in non-insulin dependent diabetes mellitus (NIDDM) and whether impaired endothelium-dependent responses in those patients are associated with increased intima-media thickness (IMT), the time sequence of their appearance and the role of individual risk factors in development of structural deterioration of arterial wall. METHODS: Ultrasound technique was used to measure brachial artery flow mediated dilation (FMD) response and carotid IMT in 38 young adults with type I diabetes aged 22-34 years and 35 healthy controls aged 22-36 years. RESULTS: Patients had significantly lower FMD than controls (4.15/2.8/ vs 11.3/3.6/, P<0.0001) and was in all diabetic patients below the mean value of controls. Further, carotid intima-media was in insulin dependent diabetes mellitus (IDDM) patients significantly thicker than in healthy subjects (0.65/0.04 vs 0.56/0.04, P=0.0001) and was related to body mass and body mass index, to the age of patients, the duration of diabetes and several risk variables. In a multivariate model FMD was most significantly and independently associated to IMT. However, significant thickening of intima-media was observed only in patients with progressed deterioration of FMD and it appeared in those subjects with long-lasting disease. IMT was also influenced by urinary albumin excretion and low-density lipoprotein (LDL) cholesterol concentration. CONCLUSIONS: Endothelium dependent FMD response is impaired in IDDM and is associated with increased carotid artery IMT. Significant thickening of intima-media appears in patients with advanced deterioration of FMD that is related to the duration of the disease. These data suggest that advanced endothelial dysfunction in IDDM may predispose to development of morphologic atherosclerotic lesions of arterial wall.     

Maladaptive arterial remodeling with systemic hypertension associated with increased concentrations in blood of plasminogen activator inhibitor type-1 (PAI-1)

Increased carotid artery intima-media thickness (IMT), but not necessarily peripheral vessel IMT, accompanies atherosclerosis. We hypothesized that IMT in a peripheral, muscular artery known to be resistant to atherosclerotic changes would increase with hypertension, thereby limiting increases in wall stress and potentially preserving endothelial cell function reflected by flow-mediated dilation (FMD). Plasminogen activator inhibitor type-1 (PAI-1) can inhibit vascular smooth muscle cell migration contributing to increased IMT. Thus, increased PAI-1 may attenuate the mural adaptive response. A high-resolution scanner designed to delineate brachial artery FMD and IMT was used in studies of previously untreated patients with essential hypertension (n = 18) and age- and gender-matched normotensive subjects (n = 15). Brachial IMT was increased with hypertension (0.36 +/- 0.07 vs 0.27 +/- 0.03 mm in controls, p <0.01), and FMD was lower (3.6 +/- 1.5% vs 7.8 +/- 3.6, p <0.01). PAI-1 antigen in blood was increased (40.5 +/- 31.8 vs 26.3 +/- 11.6 ng/ml, p <0.05). IMT and FMD correlated positively (r = 0.63, p <0.05) in hypertensive patients. FMD correlated inversely with wall stress (r = -0.57, p <0.05). IMT correlated inversely with PAI-1 (r = -0.61, p <0.05). These observations support the hypothesis that increased PAI-1 attenuated increases in neointimal vascular smooth muscle cell cellularity. Thus, increased PAI-1 may attenuate a mural, adaptive response to hypertension associated with preservation of endothelial cell function.     

Overt and subclinical hypothyroidism complicating pregnancy.

We studied the evolution of 150 pregnancies corresponding to 114 women (16-39 years old) with primary hypothyroidism. Fifty-one pregnancies (34%) were conceived under hypothyroidism: 16 overt (X +/- standard deviation [SD], thyroxine [T4]: 2.44 +/- 0.7 microg/dL; thyrotropin [TSH]: 33.4 +/- 8.82 mIU/L), and 35 subclinical hypothyroidism (T4: 6.93 +/- 1.88 microg/dL; TSH: 12.87 +/- 8.43 mIU/L); 99 pregnancies were conceived under euthyroidism while undergoing thyroid therapy. When treatment with levothyroxine was inadequate, the outcome of pregnancy was abortion in 60% of overtly hypothyroid patients and in 71.4% of subclinically hypothyroid patients, premature delivery in 20% and 7.2% respectively, and term delivery in 20% and 21.4%, respectively. When treatment was adequate, 100% of overtly hypothyroid patients and 90.5% of subclinically hypothyroid patients carried pregnancies to term; there were no abortions in any of the groups. Abortions, premature and term deliveries in patients who were euthyroid on levothyroxine at the time of conception were 4%, 11.1% and 84.9% respectively. Of the patients receiving levothyroxine therapy before conception, 69.5% had to increase the dose (mean increase 46.2 +/- 29.6 microg/d). Of 126 evaluated newborns, 110 were delivered at term while 16 were premature. Eight newborns, 4 were premature, had congenital malformations (6.3%), and 4 died. Our results show that the evolution of pregnancies did not depend on whether the hypothyroidism was overt or subclinical but mainly on the treatment received. The adequate treatment of hypothyroidism during gestation minimizes risks and generally, makes it possible for pregnancies to be carried to term without complications.     

Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise program.

OBJECTIVES: The present study aimed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation (FMD) carotid intima-media thickness (IMT) and cardiovascular risk factors (RF). BACKGROUND: Childhood obesity contributes to adult obesity and subsequent cardiovascular disease. Physical inactivity is a major RF for obesity, endothelial dysfunction, and elevated carotid IMT, culminating in early atherosclerotic disease. METHODS: Sixty-seven obese subjects (age 14.7 +/- 2.2 years) were randomly assigned to 6 months' exercise or non-exercise protocol. We examined the influence of exercises (1 h, 3 times/week) on FMD, IMT, and cardiovascular risk profile. RESULTS: Compared with lean control subjects, obese children demonstrated at baseline significantly impaired FMD (4.09 +/- 1.76% vs. 10.65 +/- 1.95%, p < 0.001), increased IMT (0.48 +/- 0.08 mm vs. 0.37 +/- 0.05 mm, p < 0.001), and a number of obesity-related cardiovascular RF. Significant improvements were observed in the exercise group for IMT (0.44 +/- 0.08 mm, p = 0.012, -6.3%) and FMD (7.71 +/- 2.53%, p < 0.001, +127%). This improvement correlated with reduced RF, such as body mass index standard deviation scores, body fat mass, waist/hip ratio, ambulatory systolic blood pressure, fasting insulin, triglycerides, low-density lipoprotein/high-density lipoprotein ratio, and low-degree inflammation (C-reactive protein, fibrinogen). CONCLUSIONS: The present study documented increased IMT, impaired endothelial function, and various elevated cardiovascular RF in young obese subjects. Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children.     

Hypothyroidism is not associated with increased carotid atherosclerosis when cardiovascular risk factors are accounted for in hyperlipidemic patients

Overt hypothyroidism is associated with an increased prevalence of cardiovascular heart disease (CHD). The role of subclinical hypothyroidism as risk factor for cardiovascular diseases is supported by recent meta-analysis. However it still remains to be established whether hypothyroidism favors atherosclerosis independently of its effects on cardiovascular risk factors, such as hypercholesterolemia or hypertension. To assess whether hypothyroidism might be a risk factor per se, we analyzed carotid lesions assessed by US examination in two large populations with similar risk factors and displaying hypo- or euthyroidism. We selected, among a population of patients referred for assessment of hyperlipidemia, 794 hypothyroid patients (TSH>4mU/L), and 1588 euthyroid patients matched for the main cardiovascular risk factors (age, gender, lipid levels, hypertension, diabetes, smoking habits and obesity). All the patients had evaluation of their arterial carotid plaques, and about half of them had measurement of carotid intima-media thickness (IMT). Our hypothyroid population included 90% of patients with normal FT4 levels (subclinical hypothyroidism). We found that neither prevalence nor severity of carotid plaques nor carotid IMT were significantly different between hypothyroid patients and controls. To assess whether thyroid hormones may predict carotid atherosclerosis, we performed multivariate regression analyses, and we showed that, in both populations of hypothyroid and euthyroid patients, neither the TSH values nor the FT4 concentrations were independent risk factors for carotid atherosclerosis. In conclusion, we showed that, among a population of hyperlipidemic patients, hypothyroidism is not associated with an increased risk for carotid atherosclerosis when cardiovascular risk factors are accounted for.     

Effects of low-dose prednisolone on endothelial function, atherosclerosis, and traditional risk factors for atherosclerosis in patients with rheumatoid arthritis--a randomized study

OBJECTIVE: To determine the influence of low-dose prednisolone on atherosclerosis, endothelial function, and risk factors for atherosclerosis in patients with early rheumatoid arthritis (RA). METHODS: At start of the first disease modifying antirheumatic drug, 67 patients with early, active RA were randomized to either 7.5 mg prednisolone daily (n = 34) or no prednisolone (n = 33). In the prednisolone group, 21 were treated for 2 years and 13 continuously. After a mean of 5 years intima-media thickness (IMT) and calculated intima-media area (cIMa) of the carotid arteries were determined by B-mode ultrasound. Endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery. RESULTS: IMT [median (interquartile range) 0.675 mm (0.58-0.82) vs 0.673 mm (0.0.62-0.80)], cIMa [13.7 mm2 (11.45-20.37) vs 14.1 mm2 (12.34-17.38)], prevalence of atherosclerotic plaques (82.3% vs 81.9%), and endothelial function [FMD% (mean +/- SD) 3.88% +/- 2.8 vs 3.74% +/- 2.9] did not differ between patients treated with and those not treated with prednisolone. There were no differences in lumen diameter of carotid arteries, or levels of lipoproteins, glucose, and blood pressure. Patients treated for at least 4 years (and currently treated) with prednisolone had a trend to higher systolic blood pressure (157 +/- 29 mm Hg) compared with untreated patients (141 +/- 28 mm Hg; p = 0.06) and had higher cholesterol levels (5.6 mmol/L +/- 1.39 vs 4.9 +/- 28; p = 0.03). In the whole cohort, age and HDL were independently associated with IMT; age, HDL, and blood pressure with cIMa; and age and serum creatinine with presence of atherosclerotic plaques. CONCLUSION: Low-dose prednisolone did not influence endothelial function and atherosclerosis in patients with RA. However, total cholesterol was higher in patients treated with prednisolone.     

Growth hormone/insulin-like growth factor axis in patients with subclinical thyroid dysfunction

ObjectiveOur aim was to evaluate serum concentrations of GH, IGF-I, and insulin-like growth factor-binding protein-3 (IGFBP-3) in patients with subclinical thyroid dysfunction before and after normalization of thyroid function.Design and methodsThe study included 51 patients (mean age 42.2 ± 1.8 years) with subclinical hypothyroidism and 30 patients (mean age 44.3 ± 2.4 years) with subclinical hyperthyroidism. A group of 37 euthyroid healthy subjects were studied as controls. Serum concentrations of TSH, FT4, FT3, GH, insulin, IGF-I, and IGFBP-3 were measured in all patients before starting therapy and after normalization of thyroid function. The dosage of levothyroxine (LT4) and antithyroid drugs was adjusted in attempt to keep the serum-free thyroxine (FT4) and thyrotropin (TSH) concentrations within the normal range.Main outcomeBaseline growth hormone levels were similar with hypothyroid group and hyperthyroid group in relation to euthyroid control subjects. Fasting serum IGF-I levels were significantly lower in the subclinical hypothyroid group compared with the control group. On the other hand, IGF-I levels of subclinical hyperthyroid patients and control group were similar. After normalization of thyroid function tests, IGF-I concentrations were increased in subclinical hypothyroid subjects, but unchanged in subclinical hyperthyroid subjects. Patients with subclinical hyperthyroidism showed slightly lower mean serum IGFBP-3 concentrations than those found in control group, but the difference was not statistically significant. Serum GH and IGFBP-3 levels were unaltered by treatment.ConclusionsIn this study, it was shown that GH–IGF axis was not affected in patients with subclinical hyperthyroidism, while it was affected in patients with subclinical hypothyroidism. That is, investigation of the axis in subclinical hyperthyroidism would not bring any extra advantages, but LT4 replacement therapy could prevent abnormalities related to GH–IGF axis in patients with subclinical hypothyroidism.     

Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease

We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound.Patients had greater carotid IMT (0.779 +/- 0.164 mm) than did controls (0.699 +/- 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 +/- 0.116 mm) than those without plaques (0.739 +/- 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease.The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.     

Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms do not affect early functional and structural changes in atherosclerosis: the Cardiovascular Risk in Young Finns study.

BACKGROUND: The present study was designed to investigate the effects of apoB XbaI and apoA-I/C-III/A-IV SstI polymorphisms to carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow-mediated vasodilatation (FMD). METHODS AND RESULTS: As part of the Cardiovascular Risk in Young Finns Study, the carotid IMT, CAC and brachial FMD of 2,265 subjects (mean age +/- SD 32 +/-5 years) were measured with ultrasonography, and genotyping of the apolipoprotein polymorphisms was performed. The frequencies of the genotypes did not differ between the groups with high (above median 0.57 mm) and low (below median) IMT, CAC or FMD. The average carotid IMT differed between the 3 apoB XbaI genotypes (ANOVA, p=0.04), but not between the apoA-I/C-III/A-IV SstI genotypes (ANOVA, p=0.53). The relationship between the polymorphisms and carotid IMT was not significant in any of the covariate-adjusted logistic and linear regression analyses. CAC and FMD were not influenced by either of the polymorphisms in ANOVA and regression analyses. CONCLUSIONS: The polymorphisms apoA-I/C-III/A-IV SstI and apoB XbaI do not seem to affect carotid artery characteristics or brachial artery FMD in young adulthood.     

Relationship between endothelial dysfunction, intima media thickness and cardiovascular risk factors in asymptomatic subjects.

AIM: The aim of the study was to evaluate endothelial function and intima media thickness (IMT) in relation to cardiovascular risk factors (RF). METHODS: We enrolled 113 patients, mean age 62 +/- 12 years; patients underwent: anamnesis, physical examination, measurement of body weight and height and blood pressure. Biochemistry variables were also measured: total cholesterol, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), triglycerides and glycemia. Vascular echography was performed to analyze flow mediated vasodilatation (FMD) at the brachial artery and IMT of the carotid and femoral arteries. RESULTS: Compared with patients without RF, patients with cardiovascular RF showed an impaired FMD (p < 0.05) and higher values of mean carotid IMT (p = 0.03). Age (p < 0.005) and diabetes (p < 0.05) were directly correlated with carotid IMT, while femoral IMT is correlated with age (p < 0.005) and male gender (p < 0.02). Regarding the relationship between endothelial function cardiovascular RF, we showed an inverse linear correlation between systolic blood pressure (p < 0.005), smoking (p < 0.05) and FMD, and concerning biochemical parameters, we founded that total cholesterol (p < 0.05) and LDL-C plasma levels (p < 0.005) were inversely correlated with FMD. Finally, we showed a lower FMD in patients with carotid and femoral IMT in comparison with patients without peripheral atherosclerosis (p = 0.01). CONCLUSIONS: The present data indicate that cardiovascular RF are associated with impaired endothelial function and increased IMT, and that the presence of carotid and femoral IMT is significantly correlated with endothelial dysfunction.     

Westernization of Chinese adults and increased subclinical atherosclerosis.

Cardiovascular event rates are much lower in China compared with developed countries. "Westernization" of diet and lifestyle in the Chinese, however, may lead to an increased prevalence of atherosclerosis-related diseases. Because carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis, we examined IMT and vascular risk profile in community-based groups of rural Chinese, Westernized urban Chinese, and urban whites. Mean IMT of the common carotid artery was measured in 348 healthy adults, aged 42+/-13 years (range 21 to 71 years); 116 subjects from rural China, 116 urban Chinese subjects living in Hong Kong or in Australia, and 116 urban Caucasians living in Australia. These 3 groups were matched for age, sex, and cigarette smoke exposure. Urban Chinese subjects had slightly better risk factor profile (higher HDL-cholesterol and lower blood pressure) compared with rural Chinese subjects. Despite this, however, the mean IMT was lowest in rural Chinese (0.50+/-0.10 mm), intermediate in urban Chinese (0.56+/-0.12 mm), and highest in urban whites (0.64+/-0.13 mm) (P<0.001 for comparisons between all groups). These differences in IMT were not altered after adjustment for the major traditional cardiovascular risk factors (serum lipids, smoking, and blood pressure or for body mass index). The influence of vascular risk factors on atherosclerosis between urban versus rural Chinese subjects was studied by multivariate regression models and by comparing the steepness of regression slopes between risk factors and IMT in the subject groups. The effects of smoking, HDL-cholesterol, and triglycerides on IMT were significantly greater in the urban compared with the rural Chinese (P<0.01). These data suggest that Westernization of Chinese subjects is associated with greater susceptibility to the pro-atherogenic effects of traditional vascular risk factors, such as lipids and smoking, and with evidence of increased IMT as a marker of subclinical atherosclerosis.     

Serum creatine kinase levels in overt and subclinical hypothyroidism

The aims of this prospective study were to determine serum levels of creatine kinase (CK) in overt and subclinical hypothyroidism; to investigate the change in CK levels with treatment; and to evaluate the relationship between free triiodsothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) levels and the degree of skeletal muscle involvement, as determined by serum CK levels. Patients with hypothyroidism presenting to our endocrinology clinic were eligible for inclusion in this study. Patients with other causes of CK elevation were excluded. We included 28 patients (25 women and 3 men, ages 41.75 +/- 13.65 years) with overt hypothyroidism, 38 patients (37 women, 1 man, ages 40.55 +/- 10.48 years) with subclinical hypothyroidism, and 30 age- and gender-matched controls (27 women, 3 men, ages 40.81 +/- 11.20 years) in the study. Serum levels of TSH, FT4, FT3, and CK were measured in all subjects. CK elevation was found in 16 patients (57%) with overt hypothyroidism and in 4 patients (10%) with subclinical hypothyroidism. Although a statistically significant elevation of CK levels was found in patients with overt hypothyroidism when compared with patients with subclinical hypothyroidism and controls (p = 0. 0001, p = 0. 01, respectively), no difference was found between the subclinical hypothyroidism and control groups (p = 0.14). In hypothyroid (overt and subclinical) patients, a positive correlation was found between CK and TSH (r = 0.432; p = 0.04), and a negative correlation between CK and FT3 (r = - 0.556; p = 0.002) and between CK and FT4 (r =0.448; p = 0.04). CK levels decreased to normal levels after thyroid function normalized with treatment. In conclusion, skeletal muscle is affected by hypothyroidism more profoundly in cases of overt hypothyroidism, less so when subclinical hypothyroidism is present.     

Low free-thyroxine levels are a risk factor for subclinical atherosclerosis in euthyroid hyperlipidemic patients.

BACKGROUND: Patients displaying overt and subclinical hypothyroidism have more cardiovascular risk factors. Consequently, they are more likely to develop atherosclerosis and cardiovascular diseases. OBJECTIVE: To analyze whether low free-thyroxine levels (FTL) would also be associated with atherosclerosis in euthyroid patients. METHODS: We selected a group of 1434 healthy euthyroid male patients without known histories of thyroid disease and with levels of thyroid-stimulating hormone values within the normal range (mean 1.70+/-0.76 mUl/l, range 0.13-4.01 mUl/l). Mean age of these patients who had been referred for assessment of hyperlipidemia was 44.6 years and mean FTL was 14.25+/-3.06 pmol/l. We divided the population according to the degree of atherosclerosis in the carotid arteries. RESULTS: Mean age, body mass index, systolic blood pressure, cigarettes/day, blood level of glucose, cholesterol levels, and fibrinogen levels were significantly higher for the patients with atherosclerotic lesions whereas mean FTL was lower for patients with carotid atherosclerosis (P = 0.0002). The relationship between FTL and carotid atherosclerosis was independent from the following cardiovascular risk factors: age, hypertension, amount of excess weight, cholesterol level, fibrinogen level, smoking status, and presence versus absence of diabetes mellitus. CONCLUSIONS: Low FTL is a risk factor for atherosclerosis in male euthyroid hyperlipidemic patients.     

The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study

AIMS/HYPOTHESIS: African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery intima-medial thickness (IMT) were present in members of The Diabetes Heart Study families. SUBJECTS AND METHODS: In a bi-racial cohort of 1,180 individuals from families enriched for members with type 2 diabetes, we calculated coronary and carotid artery calcified plaque using fast-gated helical computed tomography, and measured carotid artery IMT and clinical risk factor profiles. Generalised estimating equations were used to test for an association between measures of subclinical cardiovascular disease and ethnicity and sex. RESULTS: After adjustment for age, ethnicity and kidney function, African-Americans had significantly lower amounts of coronary artery calcified plaque (mean+/-SE) (866+/-158 vs 1,915+/-135, respectively; p=0.0466) and carotid artery calcified plaque (179+/-51 vs 355+/-27, respectively; p=0.0240) relative to whites, despite having increased carotid IMT (0.71+/-0.01 vs 0.67+/-0.004 cm, respectively; p=0.0007), and higher blood pressure, albuminuria and HbA1c. Sex-specific analyses revealed that African-American men had significantly lower coronary and carotid artery calcified atheroma than white men. In women, ethnic differences in calcified carotid artery plaque, but not coronary artery plaque, were observed. CONCLUSIONS/INTERPRETATION: In families enriched for members with type 2 diabetes, African-American men had markedly lower levels of coronary and carotid artery calcified plaque than white men, despite increased carotid artery IMT and conventional risk factors. These findings suggest that susceptibility to subclinical cardiovascular disease differs markedly according to ethnicity and sex.     

Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intima-media thickness

Finnish men have higher coronary heart disease (CHD) mortality than Swedish men do. To assess the impact of migration to a country with lower CHD mortality on subclinical atherosclerosis, we measured early functional and structural atherosclerotic vascular changes in twins discordant for migration from Finland to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the brachial artery, carotid intima-media thickness, and carotid artery compliance were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69 years, in which co-one twin had migrated more than 20 years ago permanently to Sweden. There were no significant differences in CHD risk factors except for diastolic blood pressure and body fat percentage, which were higher in Sweden. In all subjects, mean FMD was non-significantly higher in Sweden (5.7+/-4.3% vs 4.9+/-4.2%, P=0.22), but in monozygous twins the difference in FMD was highly significant (7.2+/-4.4 vs 3.7+/-2.9%, P=0.003). There was no significant difference in intima-media thickness or carotid artery compliance between Sweden and Finland. We conclude that in Finnish monozygous twins the endothelial function is better among the twins that have migrated to a country with lower CHD prevalence.     

Effects of lacidipine on vascular responses in patients with coronary artery disease

BACKGROUND: To evaluate the effects of the calcium channel blocker lacidipine on vascular responses, such as endothelial function and carotid intima-media thickness (IMT), and on levels of high-sensitivity C-reactive protein (hs-CRP) in patients with coronary artery disease (CAD). METHODS: Endothelial function was assessed by measuring the flow-mediated vasodilation (FMD) of the brachial artery and IMT was measured in the common, bifurcating, and in the internal carotid artery by using high-resolution ultrasound. The study population consisted of 96 consecutive patients [mean age 60 years, male (n) = 70] who showed at least one coronary artery narrowed by more than 50% (coronary angiography). These patients were randomly assigned to lacidipine treatment (4 mg/day, n = 48) or to a placebo (n = 48). We measured FMD, IMT, and hs-CRP prior to and after 6 months of treatment and following coronary angiography in all patients. RESULTS: Clinical and medical history revealed no significant differences between the groups. IMT of the common carotid artery was significantly diminished from 0.92 +/- 0.15 to 0.87 +/- 0.15 mm 6 months after treatment with lacidipine (p < 0.005). However, IMT of any region in the carotid artery did not show any significant changes in the placebo group. Endothelial function and hs-CRP levels were slightly improved (insignificant) in the lacidipine group. In the placebo group, there were no significant changes. CONCLUSION: Lacidipine leads to a significant reduction of the common carotid artery IMT as well as to a decrease in markers of inflammation in patients with CAD during a relatively short period (6 months).