Migration at early age from a high to a lower coronary heart disease risk country lowers the risk of subclinical atherosclerosis in middle‐aged men

Background. Study of migrants offers a natural model to assess environmental risk of coronary heart disease (CHD) in countries differing in CHD occurrence. In Sweden, CHD risk has been markedly lower than in Finland from where a large migration occurred in the 1970s. Objectives. To study the structural and functional markers of subclinical atherosclerosis in twin pairs discordant for migration with the main focus on age at migration, length of residence and integration into Swedish society after migration from a high to a lower CHD risk country. Methods. Carotid intima‐media thickness (IMT) and brachial artery endothelial function (EF) were assessed with high‐resolution ultrasound and a set of cardiovascular, socio‐economic and psychosocial risk factors were estimated in 76 middle‐aged male twin pairs discordant for migration from Finland to Sweden. Results. Men who had migrated in adolescence had lower IMT values compared with their co‐twins living in Finland (0.665 ± 0.114 vs. 0.802 ± 0.167 mm, P = 0.009). Also men who integrated well to Swedish society had lower (0.720 ± 0.154 vs. 0.799 ± 0.207 mm, P = 0.013) IMT values than their twin brothers living in Finland. Associations between IMT and migration age and between IMT and integration remained significant in multivariate analyses of several CHD risk factors. The intrapair difference in IMT was significantly associated with immigration age and integration (anova , P = 0.0082), the difference being greatest among pairs where the brother living in Sweden had migrated at early age and integrated well to Swedish society. EF was better in men who had migrated to Sweden before the age of 21 years, but not later, compared with their co‐twins in Finland (6.4 ± 4.6% vs. 3.8 ± 3.6%, P = 0.025). Conclusions. Migration at an early age and good integration are beneficial to vascular health associated with moving from a high to a lower CHD risk country, suggesting that an environment‐sensitive period influences atherogenesis before adulthood.     

Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men

Endothelial dysfunction has been reported to be the initial step in atherosclerosis. A noninvasive technique that uses ultrasound to measure the intima-media thickness of the carotid artery has been applied to evaluate localized atherosclerosis. This study was undertaken to elucidate whether endothelial dysfunction in the brachial artery is related to the intima-media thickness of the carotid artery. Thirty-four men with atherosclerosis (mean+/-SE age 61+/-2 years) and 33 age-matched men without clinical atherosclerosis were examined. The intima-media thickness and plaque formation of the common carotid artery were assessed by B-mode ultrasonography. We also noninvasively measured brachial artery diameter by the same ultrasound machine when the subjects were at rest, during reactive hyperemia, which causes endothelium-dependent vasodilatation, and after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. The atherosclerosis group had a significantly greater intima-media thickness of the common carotid artery than did the control group (1. 02+/-0.04 versus 0.91+/-0.03 mm, P<0.05). The flow-mediated diameter (FMD) increase (percent FMD=DeltaD/D x 100) in the atherosclerosis group was significantly smaller than that in the control group (2. 8+/-0.4% versus 5.1+/-0.6%, P<0.01). A significant negative correlation between the intima-media thickness of the carotid artery and percent FMD was found in all of the subjects. On multiple regression analysis, percent FMD showed a significant negative correlation with the intima-media thickness of the common carotid artery. These findings support the concept that endothelial dysfunction is significantly related to atherogenesis.     

Low serum bilirubin levels are independently and inversely related to impaired flow-mediated vasodilation and increased carotid intima-media thickness in both men and women

BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol and its oxidative modification have been described to be involved in the process of atherogenesis. Bilirubin, an antioxidant, prevents oxidative modification of LDL and therefore may protect from atherosclerosis and coronary heart disease (CHD). Impaired brachial artery flow-mediated dilatation (FMD), which means endothelial dysfunction (ED) and carotid intima-media thickness (IMT) are predictors for the development and progression of atherosclerosis. In the present study, FMD and IMT were studied in healthy subjects with lower and higher serum bilirubin concentrations in physiological ranges. METHODS: Ninety-one healthy subjects between 25 and 45 years of age (47 with lower and 44 with higher serum bilirubin concentrations) were included in this study. Carotid IMT and brachial artery flow-mediated dilatation was measured by means of high-resolution vascular ultrasound. FMD was assessed by establishing reactive hyperemia and endothelium-independent dilatation (EID) was determined by using sublingual isosorbide dinitrate. RESULTS: EDD in subjects with lower serum bilirubin concentrations was significantly worse than in those with higher serum bilirubin concentrations (11.6+/-4.4% versus 7.2+/-4.7%, respectively, p<0.0001). EID measurements were not significantly different between the groups (16+/-5.1% versus 16.8+/-7%, respectively). In addition, carotid IMT was significantly greater in subjects with lower serum bilirubin concentrations (0.5+/-0.13 mm versus 0.42+/-0.07 mm, p<0.0001). Furthermore, FMD in women with lower serum bilirubin concentrations was significantly lower than in women with higher serum bilirubin concentrations (11.5+/-4.9% and 17.5+/-4.7%, respectively, p<0.001). Accordingly, men with lower serum bilirubin concentrations had significantly lower FMD as compared to hyperbilirubinemic ones (11.7+/-3.6% versus 16.7+/-4.8%, respectively, p=0.009). Conversely, carotid IMT was significantly greater in both women and men with lower serum bilirubin concentrations compared to the subjects with elevated serum bilirubin concentrations (0.51+/-0.08 versus 0.41+/-0.08, p<0.001; 0.55+/-0.12 versus 0.40+/-0.07, p=0.002, in women and men, respectively). CONCLUSION: The healthy subjects with lower serum bilirubin concentrations show significant ED and increased carotid IMT, which are predictors for atherosclerosis.     

Flow-mediated vasodilatation of the brachial artery and intima-media thickness of carotid artery in never-treated subjects.

AIM: Data on the association between brachial artery flow-mediated dilatation (FMD) and common carotid intima-media thickness (IMT) are contrasting. The present study investigated the relationship between FMD and IMT and carotid atherosclerosis in never treated subjects. METHODS: Seventy-seven subjects were investigated: 46 had no coronary heart disease (CHD) risk factors, 21 had only one, and 10 had more than one risk factor. IMT of the common carotid was measured by ultrasonography and FMD was evaluated according to standardized methods. RESULTS: IMT increased with increasing number of risk factors (0.66+/-0.12, 0.69+/-0.12 and 0.8+/-0.17 mm, respectively, ANOVA P<0.05). FMD decreased with increasing number of risk factors (10.44+/-5.2, 6.52+/-7.11 and 7.35+/-4.42%, respectively, P<0.05). Endothelium-independent vasodilatation was similar in the 3 groups. IMT and FMD did not correlate neither in subjects without risk factors (r=-0.151, P=0.3), nor in those with 1 (r=-0.196, P=0.4) or with 2 or more risk factors (r=-0.387, P=0.2), while in the group as a whole the correlation was borderline significant (r=-0.217, P=0.058). Eleven subjects had carotid atherosclerosis and higher values of IMT, but not reduced FMD. In multiple regression analysis, diabetes and IMT, but not FMD, were associated with carotid atherosclerosis. CONCLUSIONS: The present findings indicate that, in never treated subjects, FMD is not strictly associated with IMT or atherosclerosis of the carotid arteries.     

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.     

冠心病患者冠状动脉病变血管数与高敏C反应蛋白、颈动脉斑块分级和内皮功能的相关性

目的探讨冠心病患者冠状动脉病变血管数与高敏C反应蛋白(hsCRP)、内皮依赖血管舒张功能、颈动脉内膜中层厚度(IMT)和斑块积分的相关性。方法采用高分辨率血管超声法检测76例冠心病患者与30例非冠心病对照组肱动脉血流介导的内皮依赖性血管舒张功能(FMD)、颈动脉IMT及斑块积分;并检测患者血液中hsCRP水平,对冠心病患者进行冠状动脉造影,根据冠状动脉病变血管数将冠心病患者分为3组:单支病变组、双支病变组及三支病变组。结果冠心病患者的血浆hsCRP显著高于对照组,FMD在冠心病各亚组中明显降低,与对照组比较差异有统计学意义(均为P<0.05);IMT在冠心病组中明显增厚,与对照组比较差异有统计学意义(均为P<0.05);颈动脉斑块积分在冠心病各亚组间比较差异有统计学意义(P<0.05)。冠心病患者冠状动脉病变血管数与血浆hsCRP及斑块积分呈正相关,与FMD呈负相关。结论血浆hsCRP、FMD及颈动脉斑块积分的检测与冠心病患者冠状动脉病变支数相关。     

Arterial structure and function in young adults with the metabolic syndrome: the Cardiovascular Risk in Young Finns Study.

AIMS: To study the relations between the metabolic syndrome (MS) and subclinical atherosclerosis in young adults. METHODS AND RESULTS: International Diabetes Federation (msIDF), National Institute of Health Adult Treatment Panel III (msNCEP), and European Group for the Study of Insulin Resistance (msEGIR) definitions of MS were related to carotid artery intima-media thickness (cIMT), brachial flow-mediated dilatation (FMD), and carotid artery compliance (CAC) in 2163 Finnish adults (aged 32 +/- 5years). All definitions associated with increased cIMT and decreased CAC in both sexes. The cIMT values (mean+/-SD) were 0.576 +/- 0.088 mm in subjects without the syndrome, 0.615 +/- 0.102 mm in msIDF, 0.617 +/- 0.104 mm in msNCEP, and 0.607 +/- 0.097 mm in msEGIR (P < 0.0001). Corresponding CAC values were 2.26 +/- 0.72, 1.76 +/- 0.66, 1.73 +/- 0.66, 1.72 +/- 0.66%/10 mmHg (P < 0.001). Impaired brachial FMD was not related to MS but it modified the relations between MS and cIMT: MS correlated with increased cIMT in subjects with an impaired FMD response (P = 0.003) but not in subjects with an enhanced FMD response (P = 0.75). CONCLUSION: All current definitions of MS identify a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis.     

Intima-media complex of both the brachial artery and the common carotid artery are associated with left ventricular hypertrophy in patients with previous myocardial infarction

OBJECTIVES: Prospective trials have established intima-media thickness (IMT) of the carotid artery, flow-mediated dilation (FMD) of the brachial artery and cardiac left ventricular hypertrophy (LVH) as predictors of cardiovascular events. The aim of this study was to examine the relationship between intima-media complex of the brachial artery to FMD, intima-media complex of the common carotid artery and cardiac hypertrophy in patients with coronary heart disease. METHODS AND PROCEDURES: Cross-sectional design. Procedures were undertaken within the Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. A total of 123 patients with a previous acute myocardial infarction (MI) were investigated. Calculated intima-media area (cIMa) of the brachial and common carotid arteries and FMD of the brachial artery and left ventricular dimensions were examined. RESULTS: The brachial cIMa was significantly associated with age, p-triglycerides, common carotid cIMa, ejection fraction, septum thickness, posterior wall thickness and left ventricular mass index (P < 0.05). Brachial cIMa also tended to be associated with systolic blood pressure (P = 0.056). Common carotid cIMa was significantly associated with age, systolic blood pressure, brachial cIMa, FMD and septum thickness (P < 0.05). FMD was significantly associated with age and carotid cIMa (P < 0.05). CONCLUSION: Both cIMa of the common carotid artery and the cIMa of the brachial artery were independently and significantly associated with ventricular septum thickness of the heart in patients with previous myocardial infarction.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.     

Endothelial-dependent vasodilation is impaired in children with sickle cell disease

Impairment of endothelial-dependent vasodilation has been demonstrated in adults with sickle cell anemia (SCA). We enrolled 21 SCA children, mean age 10.4+/-3.3 yrs, and 23 Afro-Caribbean controls. We examined flow-mediated (FMD) and nitroglycerine-mediated (GTNMD) dilation of the brachial artery, using echotracking techniques, and measured intima-media thickness (IMT) and mechanical properties of the common carotid artery. FMD was significantly decreased in SCA children vs controls (5.6+/-0.2 vs 8.0+/-0.2%, p=0.008), while IMT, stiffness of the common carotid artery, and GTNMD were comparable. In conclusion, endothelial dysfunction is present as early as childhood in SCA patients.     

Relation of apolipoprotein E polymorphism to markers of early atherosclerotic changes in young adults--the Cardiovascular Risk in Young Finns Study.

BACKGROUND: Carotid artery intima-media thickness (IMT), which is measured by ultrasound, is used in the assessment of early atherosclerotic changes, and has been associated with apolipoprotein E (APOE) polymorphism in many studies comprising elderly subjects. However, results are still inconclusive and data relating to young adults are missing. Whether common APOE polymorphism is related to carotid IMT was studied in a population of young adults. Also brachial flow-mediated dilatation (FMD) and carotid artery compliance (CAC) were determined to clarify their relation to this genetic factor. METHODS AND RESULTS: A total of 1,188 young adults (aged 24-39 years) participating in the Cardiovascular Risk in Young Finns Study with complete data of common APOE polymorphism underwent a carotid and brachial ultrasound. Patients' lipid levels and blood pressure were also examined. There was no significant association between the APOE phenotypes and carotid IMT, brachial FMD or CAC either in young men or in young women. The results were similar for systolic and diastolic blood pressure. In the same population, the well-known association between APOE phenotypes and lipids was seen. CONCLUSIONS: Common APOE polymorphism does not seem to be an independent genetic determinant of carotid IMT, brachial FMD or CAC.     

Circulating estradiol is an independent predictor of progression of carotid artery intima-media thickness in middle-aged men

CONTEXT: Estrogen treatment of men with prostate cancer is associated with increased cardiovascular morbidity and mortality; however, the role of endogenous estrogen levels for atherosclerotic disease in men is unknown. OBJECTIVE: The objective of the study was to determine whether endogenous serum estradiol (E2) levels predict the progression of carotid artery intima-media thickness in men. DESIGN, SETTING AND PARTICIPANTS: This was a population-based, prospective cohort study (the Atherosclerosis and Insulin Resistance study) conducted in G?teborg, Sweden, among 313 Caucasian men without cardiovascular or other clinically overt diseases. Carotid artery intima-media thickness, an index of preclinical atherosclerosis, was measured by ultrasound at baseline (58 yr of age) and after 3 yr of follow-up. Serum sex hormone levels and cardiovascular risk factors (body mass index, waist to hip ratio, systolic blood pressure, serum triglycerides, plasma c-peptide, and smoking status) were assessed at study entry. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: Association between baseline total and free E2 levels and progression of carotid intima-media thickness over 3 yr with adjustments for cardiovascular risk factors was measured. RESULTS: In univariate analyses, both total and free E2 levels at baseline were positively associated with the annual change in intima-media thickness. In linear regression models including E2 and cardiovascular risk factors, low-density lipoprotein and high-density lipoprotein cholesterol and E2 were identified as independent predictors of progression of carotid artery intima-media thickness (total E2 beta = 0.187, P = 0.001; and free E2 beta = 0.183, P = 0.003). CONCLUSIONS: Circulating E2 is a predictor of progression of carotid artery intima-media thickness in middle-aged men. Further studies are needed to investigate the role of endogenous E2 for incident cardiovascular disease events.     

40-Year CHD Mortality Trends and the Role of Risk Factors in Mortality Decline: The North Karelia Project Experience

In the 1960s and early 1970s, coronary heart disease (CHD) mortality in Finland was the highest in the world, and within Finland, mortality was particularly high in the eastern part of the country. The North Karelia Project, the first large community-based cardiovascular diseases prevention program was established in 1972 to reduce the extremely high CHD mortality through behavioral change and reduction of the main cardiovascular disease risk factors among the whole population of North Karelia, the easternmost province of Finland. During the 40-year period from 1972 to 2012, smoking prevalence, serum total cholesterol, and systolic blood pressure declined markedly, except a small increase in serum cholesterol levels between 2007 and 2012. From the early 1970s to 2012, CHD mortality decreased by 82% (from 643 to 118 per 100,000) among working-age (35 to 64 years) men. Among working-age women, the decline was 84% (from 114 to 17 per 100,000). During the first 10 years, changes in these 3 target risk factors explained nearly all of the observed mortality reduction. Since the mid-1980s, the observed reduction in mortality has been larger than the predicted reduction. In the early 1970s, premature CHD mortality (35 to 74 years) was about 37% higher among Eastern Finnish men and 23% higher among Eastern Finnish women, compared with men and women in Southwestern Finland. During the last 40 years, premature CHD mortality declined markedly in both areas, but the decline was larger in Eastern Finland and the mortality gap between the two areas nearly disappeared.     

Cardiovascular prognostic value of vascular involvement in Behcet's disease

We measured carotid artery intima-media thickness (IMT), brachial artery flow mediated dilation (FMD), and coronary flow reserve (CFR) in 38 Behcet's disease (BD) patients without vascular involvement, 15 BD patients with vascular involvement, and 35 control subjects. BD patients with and without vascular involvement were similar regarding carotid IMT (0.52+/-0.14; 0.51+/-0.09; 0.46+/-0.09; P=0.051), and brachial FMD (16.3+/-6.8; 16.5+/-9.1). CFR values were significantly impaired in BD patients compared to the controls; however the BD patients with and without vascular involvement were similar regarding CFR (2.66+/-0.45; 2.62+/-0.48; 2.91+/-0.53, P=0.007 with and without vascular involvement and the controls, respectively). Endothelial and coronary microvascular functions are compromised in BD patients without vascular involvement as remarkably as that in patients with vascular involvement.     

Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and Swedish men: the LiVicordia study

Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Link?ping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Link?ping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P < 0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P < 0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and beta-carotene (inversely) significantly contributed to a high total ultrasound score (r2 = 0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.     

高血压前期颈动脉内-中膜厚度及血管内皮舒张功能的变化

目的探索高血压前期外周动脉血管粥样硬化和血管内皮功能的改变。方法检测颈动脉内-中膜厚度（IMT）和肱动脉内皮舒张功能。结果高血压前期组颈动脉分叉、颈总动脉处内-中膜厚度均较正常血压组增厚（P〈0．05）;高血压前期组反应性充血后肱动脉内径变化率（FMD）显著低于正常血压组（P〈0．05）;含服硝酸甘油后肱动脉内径FMD高血压前期组与正常血压组无明显差异（P〉0．05）。结论高血压前期已存在颈动脉内-中膜增厚,血管内皮功能已经受损。     

Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: the cardiovascular risk in Young Finns Study.

AIMS: The objective was to produce reference values and to analyse the associations of age and sex with carotid intima-media thickness (IMT), carotid compliance (CAC), and brachial flow-mediated dilatation (FMD) in young healthy adults. METHODS AND RESULTS: We measured IMT, CAC, and FMD with ultrasound in 2265 subjects aged 24-39 years. The mean values (mean +/- SD) in men and women were 0.592 +/- 0.10 vs. 0.572 +/- 0.08 mm (P < 0.0001) for IMT, 2.00 +/- 0.66 vs. 2.31 +/- 0.77%/10 mmHg (P < 0.0001) for CAC, and 6.95 +/- 4.00 vs. 8.83 +/- 4.56% (P < 0.0001) for FMD. The sex differences in IMT [95% confidence interval (CI) for sex difference -0.013 to 0.004 mm, P = 0.37] and CAC (-0.01 to 0.18%/10 mmHg, P = 0.09) became non-significant after adjustments with risk factors and carotid diameter. In FMD, the sex difference was unaltered after adjustments for risk factors, but was reversed after adjustment with brachial diameter (95% CI 0.18-1.32%, P < 0.01). With aging, IMT increased 5.7 +/- 0.4 microm/year and CAC decreased 0.042 +/- 0.003%/10 mmHg/year. The association of age with IMT and CAC was slightly attenuated (12 and 22%, respectively) after adjustments with risk factors, but remained significant (both P < 0.0001). Aging was not significantly related to brachial FMD (P = 0.16). CONCLUSION: Reference values produced in the present study can be utilized in the cardiovascular risk stratification among young people. Sex differences in the markers of subclinical atherosclerosis were mostly explained by differences in risk factors and vessel size. This emphasizes the importance of risk factor control in the prevention of atherosclerosis in young adults.     

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.     

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.     

The indexes of arterial structure and function in women with simple obesity: a preliminary study

Obesity is associated with an increased risk of cardiovascular disorders. The aim of the present study was to compare the indexes of arterial structure and function in women with simple obesity and healthy individuals. Twenty-two women with simple obesity (body mass index [BMI]: 33.6 +/- 2.9 kg/m(2), age: 29.7 +/- 6.2 years), and 34 healthy women were included in the study. Healthy subjects were divided into two subgroups according to their age (<35 and >45 years): Control A-16 young women (age <35 years, BMI: 24.0 +/- 3.0 kg/m(2)), and Control B-18 older women (age >45 years, BMI: 25.8 +/- 2.9 kg/m(2)). Noninvasive, high-resolution, vascular ultrasound was used to evaluate the endothelial-dependent vasodilatation: flow-mediated dilatation of brachial artery (FMD); the arterial structure: intima-media thickness (IMT) of common carotid artery (CCA); and the compliance parameters corresponding to structural changes in large arteries (PWV: pulse wave velocity; PP: pulse pressure; TAC: total arterial compliance; Ao C: aorta compliance, CCA C: CCA compliance, stiffness indexes). Endothelial-dependent vasodilatation as represented by FMD was comparable in the obese group (16.8% +/- 7.9%; median: 15.5%) and healthy subjects (Control A: 14.1% +/- 4.7%; median: 13.6%; Control B: 13.9% +/- 6.5%; median: 13.0%). The mean value of IMT was significantly increased (P < 0.05) in Control B group (0.67 +/- 0.07 mm) in comparison to both obese patients (0.58 +/- 0.09 mm) and Control A group (0.53 +/- 0.05 mm). The compliance parameters (PWV, AoC, CCA C, stiffness indexes) were impaired in obese patients and Control B patients as compared to Control A individuals. PWV and stiffness indexes were significantly increased, and the AoC, CCA C-diameter, CCA C-area were significantly decreased. Simple obesity constitutes an important risk factor accelerating arterial stiffness in women.