Advanced endothelial dysfunction in diabetic patients with multiple risk factors; importance of insulin resistance

AIM: Endothelial dysfunction is considered an early event in the development of atherosclerosis. The present study was undertaken to determine whether the accumulation of cardiovascular risk factors and insulin resistance are associated with endothelial function in diabetic patients.METHODS: 101 patients with type 2 diabetes without macroangiopathy stratified by the number of cardiovascular risk factors (dyslipidemia, hypertension, obesity) and 9 normal control subjects were studied for vascular endothelial functions by measuring flow-mediated vasodilation (FMD) using a high-resolution ultrasound method, brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (IMT), and the ankle-brachial index (ABI).RESULTS: FMD negatively correlated with baPWV and carotid IMT, and positively correlated with ABI. FMD was significantly lower in diabetic patients associated with 3 other risk factors than in those with diabetes alone. In subjects with fasting plasma glucose < or = 140mg/dL, FMD showed significant negative correlations with fasting insulin levels and homeostasis model assessment (HOMA)-R. Multivariate analysis revealed that insulin resistance as represented by HOMA-R and systolic blood pressure showed a significant association with impaired FMD.CONCLUSION: The present results suggest that the accumulation of cardiovascular risk factors is associated with endothelial dysfunction in diabetic patients, and that insulin resistance as well as high blood pressure could play a pathogenic role in the development of endothelial dysfunction.     

Can measurement of the intima-media thickness of the carotid artery improve the diagnostic value of exercise stress tests?

OBJECTIVE: The diagnostic value of the exercise electrocardiogram (ECG) for the detection of coronary artery disease is hampered by a high proportion of equivocal results, especially in asymptomatic patients. The intima-media thickness of the carotid artery correlates well with the degree of atherosclerosis, also in other vascular beds, such as the coronary arteries. The aim of this study is to evaluate whether measurements of intima-media thickness can improve the diagnostic value of stress ECG in the detection of coronary artery disease. METHODS: Patients without a history of vascular disease and with equivocal exercise stress ECG results were included. The intima-media thickness was measured with high resolution echography at the posterior wall of the common carotid artery, using an automated edge-tracking method. The diagnosis of coronary artery disease was based on the presence of reversible perfusion defects on exercise MIBI-scintigrams. RESULTS: A total of 90 patients (46 men, 44 women) with a mean age of 53.7 years were included. The MIBI-scintigraphy was positive in 17. There was no difference in mean intima-media thickness between MIBI positive and MIBI negative patients (635.76 +/- 84.56 microm and 643.89 +/- 107.06 microm, respectively, p = 0.8). Using multiple regression analysis, neither intima-media thickness measurements, nor classic risk factors could predict the result of MIBI-scintigraphy. Intima-media thickness was mainly influenced by age and hypertension. CONCLUSIONS: In this study, neither intima-media thickness measurements, nor classic risk factors could improve the diagnostic value of stress ECG in the detection of coronary artery disease. In case of equivocal stress results, additional cardiovascular imaging techniques remain recommended.     

Relationships between perioperative vascular endothelial function and cardiovascular changes

Background Perioperative cardiovascular complications occurred frequently,especially coronary heart disease,as atherosclerosis risk factors in patients.To explore the perioperative arterial vascular endothelial function and carotid intima-media thickness(IMT) as atherosclerosis early pathological changes of alternative indicators forecast the possibility of cardiovascular complications.Methods We selected surgery patients 150 cases:including atherosclerosis risk factors group(ASF group):73 cases,among them,22 cases had carotid artery atherosclerosis plaque(ASF:IMT Plaque) and 51 cases had no plaque(ASF:NO-IMT Plaque);and non-risk factors group(NO-ASF group):77 cases,among them,18 cases had carotid artery atherosclerosis plaque(NO-ASF:IMT Plaque) and 59 cases had no plaque(NO-ASF:NO-IMT Plaque).Arterial vascular endothelial function was measured as flow-mediated dilation(FMD) of the brachial artery using high-resolution B-mode ultrasonic device,for one day before operation(the baseline of value),on two hours from recovery after general anesthesia,the first day after operation,the fifth days after operation.Results FMD of two groups on two hours was reduced,compared with the baseline,but FMD of ASF group was decreased significantly(P = 0.032);FMD of ones further was increased on Day 1 and Day 5,but NO-ASF group was increased significantly(P < 0.05);FMD of the baseline and atherosclerosis risk factors was negatively correlated(R =-0.216,P = 0.023).FMD of ASF:IMTP group was decreased significantly respectively in four times,compared with the ASF:NO-IMTP group(P = 0.034,P = 0.009,P = 0.001 and P = 0.017).FMD of NO-ASF:IMTP group was decreased significantly respectively in four times,compared with the NO-ASF:NO-IMTP group(P = 0.006,P = 0.005,P = 0.000 and P = 0.000).Pulse pressure(PP) was not different on Day 1(P = 0.26),and was different between the two groups in the remaining three periods(P = 0.035,P = 0.040 and P = 0.014);SBP was not different between the basic value(P > 0.05),there were differences in the other three times(P < 0.05).While Nitroglycerin-induced dilation(NTG) was stable throughout.Conclusions Arterial endothelial function was correlative with atherosclerosis risk factors,and that EDD and IMT as atherosclerosis alternative indicators forecast cardiovascular and cerebrovascular events after surgery is feasible.     

Carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with and without coronary artery disease

BACKGROUND: Carotid intima-media thickness and pulse wave velocity are non-invasive markers of atherosclerosis and have been shown to reliably predict presence and extent of atherosclerotic vascular disease. However, studies examining their association with each other have shown inconsistent results. Hence it was sought to assess correlation between carotid intima-media thickness and pulse wave velocity in patients with and without coronary artery disease. METHODS AND RESULTS: Sixty-four patients with angiographically proven coronary artery disease and 84 age-matched individuals without coronary artery disease but having one or more conventional cardiovascular risk factors were included in the study. Individuals with established cerebrovascular disease and peripheral vascular disease were excluded from the study. Carotid intima-media thickness of far wall was measured at three predefined sites (distal common carotid, carotid bifurcation and proximal internal carotid artery) on each side. Brachial-ankle pulse wave velocity was measured non-invasively using VP 1000 (Colin Corporation) automated ABI/ PWV analyzer. There was no significant difference in gender and presence of cardiovascular risk factors in the two groups. Mean and maximum carotid intima-media thickness and brachial-ankle pulse wave velocity were all significantly higher in coronary artery disease patients as compared to patients without coronary artery disease (0.842 v. ( 0.657 mm, p <0.0001; 1.076 v. 0.795 mm, p <0.0001; 1708.63 v. 1547.26 cm/s, p <0.0004 respectively). There was a significant correlation between brachial-ankle pulse wave velocity and both mean and maximum carotid intima-media thickness in patients with coronary artery disease (r = 0.47, p <0.0001 and r=0.41, p < 0.0008 respectively) but not in individuals without coronary artery disease (r=0.01 and -0.1 respectively). CONCLUSIONS: Presence of significant correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with coronary artery disease but absence of the same in individuals without major atherosclerotic vascular disease suggests that the correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity becomes stronger with increasing extent of atherosclerosis.     

Impaired endothelial function in patients with ankylosing spondylitis

OBJECTIVE: In recent years, accelerated atherosclerosis and increased risk of cardiovascular events have been described in patients with rheumatic disease, particularly for rheumatoid arthritis and systemic lupus erythematosus. However, the link between inflammation, atherosclerosis and ankylosing spondylitis is controversial. We evaluated the degree of atherosclerosis and endothelial function of ankylosing spondylitis patients ultrasonographically. METHODS: Fifty-four patients with ankylosing spondylitis (37 +/- 11 yr, 29 males, 25 females) and 31 healthy controls (35 +/- 9 yr, 16 males, 15 females) were consecutively enrolled in the study. Serum lipids, creatinine, glucose, and acute-phase proteins were assessed. The Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were also evaluated. Flow-mediated dilatation and endothelium-independent dilatation of the brachial artery and intima-media thickness of the common carotid artery were measured sonographically. RESULTS: Left, right and averaged intima-media thickness of the common carotid artery did not show a statistically significant difference between the ankylosing spondylitis and control groups. However, flow-mediated dilatation was significantly lower in the ankylosing spondylitis patients (14.1 +/- 6.7 vs 17.6 +/- 8%; P = 0.03). Likewise, nitroglycerin-induced dilatation was lower in the patient group, but the difference was not significant (16.4 +/- 6.8 vs 19.8 +/- 10%; P = 0.07). No correlation was detected between flow-mediated dilatation and age, sex, serum lipids, CRP, ESR, smoking habits and disease activity scores. Intima-media thickness of the common carotid artery was positively correlated with age and BASMI score (r = 0.55, P = 0.00; r = 0.22, P = 0.04, respectively). CONCLUSION: This study demonstrates impairment of endothelial function in ankylosing spondylitis.     

Endothelial dysfunction, intima-media thickness and coronary reserve in relation to risk factors and Framingham score in patients without clinical atherosclerosis

BACKGROUND: Endothelial dysfunction, decreased coronary flow reserve (CFR) and increased intima-media thickness (IMT) are related to atherosclerosis and can be assessed non-invasively by echography. OBJECTIVES: In order to describe the relationship between these parameters and with cardiovascular risk, this study investigated them simultaneously in patients without clinical atherosclerosis. METHODS: A total of 106 subjects were studied, 91 with and 15 without cardiovascular risk factors. Cardiovascular disease was excluded in all cases. Doppler ultrasound was used to analyse endothelium-dependent vascular dilation in the brachial artery, IMT in the common carotid artery and CFR in the left anterior artery. RESULTS: Patients with cardiovascular risk factors had impaired flow-mediated dilation (FMD; 3.7 +/- 3.2 versus 11.6 +/- 4.4%, P = 0.000); greater IMT (0.89 +/- 0.3 versus 0.56 +/- 0.14 mm, P = 0.000) and lower CFR (2.7 +/- 0.9 versus 4 +/- 1.2, P = 0.000). Correlation was found between IMT and FMD r = -0.240, (P = 0.013), IMT and CFR, r = -0.384 (P = 0.000), and between FMD and CFR of r = 0.289 (P = 0.007). All patients with IMT greater than 1 mm showed depressed FMD, most of them with low values of CFR, but patients with reduced FMD or CFR did not necessarily show increased IMT. There was a significant correlation between the three parameters and the Framingham risk score. Multiple linear regression analysis showed that IMT was the only factor related to the Framingham score. CONCLUSION: In patients without clinical atherosclerotic disease, cardiovascular risk factors are associated with impaired FMD, CFR and increased IMT. Even though a correlation between these changes was found, they showed different dependence on cardiovascular risk factors and with global risk, IMT being the best correlated with the Framingham score.     

Carotid Intima-Media Thickness and Brachial Artery Flow-Mediated Dilatation in Patients with and without Metabolic Syndrome

BACKGROUND, Metabolic syndrome has recently emerged as a marker of future cardiovascular risk. However its incremental value for this purpose, over conventional cardiovascular risk factors and diabetes mellitus in particular, is debated. The present study was conducted to determine the extent of subclinical atherosclerosis in patients with metabolic syndrome, and compare it with the same in individuals with cardiovascular risk factors not having metabolic syndrome. METHODS, A total of 156 individuals seeking outpatient cardiac consultation for various indications were included in the study and were divided into four groups - group 1: cardiovascular risk factors present but not metabolic syndrome (n = 60) : group 2 : metabolic syndrome without diabetes mellitus or coronary artery disease (n = 21) ;group 3: metabolic syndrome with diabetes mellitus without coronary artery disease ( n = 27) ;and group 4:patients with documented coronary artery disease (n = 48). Metabolic syndrome was diagnosed on the basis of Adult Treatment Panel III (ATPIII) criteria. All patients underwent assessment of carotid intima-media thickness and brachial artery flow-mediated vasodilatation. RESULTS, Both carotid intima-media thickness and brachial artery flow-mediated vasodilatation were similar in groups 1 and 2 (carotid intima-media thickness: 0.687 -/+ 0.13mm and 0.706 -/+0.23mm, p = 0.963; brachial artery flow-mediated vasodilatation: 11.80 -/+ 5.16% and 12.87 -/+ 7.04%, respectively, p =0.883) , but group 3 patients had significantly higher carotid intima-media thickness (0.774 +/- 0.15mm, p = 0.047) and significantly lower brachial artery flow-mediated vasodilatation (7.37 -/+ 6.12%, p -/+ 0.007) as compared to group 1 patients. There was no significant difference in the two parameters between groups 3 and 4 (carotid intima-media thickness in group 4:0.789 -/+ 0.16mm,p = 0.976 and brachial artery flow-mediated vasodilatation:5.86 -/+ 3.85%, p -/+ 0.709). CONCLUSIONS, In absence of diabetes mellitus, metabolic syndrome was not associated with greater extent of subclinical atherosclerosis compared to individual cardiovascular risk factors. Presence of diabetes mellitus, however, resulted in significant endothelial dysfunction and evidence of subclinical atherosclerosis, similar to that seen in patients with already established coronary artery disease.     

Soluble Fas ligand and atherosclerosis in hypertensive patients

BACKGROUND : The Fas-Fas ligand (FasL) system is involved in apoptosis in many types of cells. Recently, the expression of FasL on endothelial cells was reported. FasL is cleaved by a metalloproteinase and released in serum as soluble FasL (sFasL). Vasoactive substances, including metalloproteinase, are modulated by endothelial dysfunction. Advanced atherosclerosis and impaired endothelial function are seen in hypertensive patients. The inflammatory response has an important role in the development of atherosclerosis, whereas C-reactive protein (CRP) is associated with the presence and severity of atherosclerosis. OBJECTIVE : To measure the intima-media thickness of the common carotid artery and evaluate the relationship between atherosclerosis and serum sFasL concentrations in hypertensive patients. PATIENTS AND MAIN OUTCOME MEASURES : Forty-seven patients with hypertension participated in the study. The intima-media thickness of the common carotid artery was evaluated by ultrasound imaging. Serum concentrations of sFasL were measured by enzyme-linked immunosorbent assay. RESULTS : Intima-media thickness correlated positively with age (r = 0.362, P = 0.012) and sFasL concentrations (r =0.332, P = 0.022), and negatively with creatinine clearance (r = -0.399, P = 0.0055). A general linear model analysis with atherosclerotic risk factors and sFasL revealed that age, sFasL, high-density lipoprotein-cholesterol and systolic blood pressure were significantly associated with intima-media thickness. Furthermore, we demonstrated that serum sFasL is directly associated with CRP concentration (r = 0.316, P = 0.030). CONCLUSIONS : These results indicated that serum sFasL concentration is associated with atherosclerosis and inflammatory disease, in patients with hypertension.     

Accelerated atherosclerosis in patients with Wegener's granulomatosis

BACKGROUND: Several autoimmune disorders are complicated by excess cardiovascular disease. In addition to traditional risk factors, non-traditional risk factors such as endothelial activation and excessive vascular remodelling might be determinants of the progression of atherosclerosis in patients with an autoimmune disease. OBJECTIVE: To evaluate whether patients with Wegener's granulomatosis (WG) have an increased prevalence of atherosclerosis and to determine predisposing factors. METHODS: 29 WG patients (19 men; mean (SD) age, 53 (14) years) with inactive disease and 26 controls (16 men; age 53 (15) years) were studied. Common carotid intima-media thickness (IMT) was measured by ultrasound. In all individuals traditional risk factors for cardiovascular disease were determined. High sensitivity C reactive protein (hsCRP) was measured. Endothelial activation was assessed by measuring thrombomodulin, vascular cell adhesion molecule-1, and von Willebrand factor. As a marker of vascular remodelling matrix metalloproteinases (MMP-3 and MMP-9) and TIMP-1 were measured. RESULTS: IMT was increased in WG patients compared with controls (p<0.05). No differences in traditional risk factors and endothelial activation markers between patients and controls were found. Levels of hsCRP, MMPs, and TIMP-1 were increased in WG patients (p<0.05). CONCLUSIONS: Increased IMT found in WG patients cannot be explained by an increased prevalence of traditional risk factors. Although endothelial activation markers in WG patients with inactive disease were not increased, the raised levels of hsCRP, MMPs, and TIMP-1 suggest that enhanced inflammation and excessive vascular remodelling are contributing factors in the development of accelerated atherosclerosis in WG.     

Endothelial function in patients with vasculogenic erectile dysfunction

OBJECTIVES: Erectile dysfunction (ED) commonly coexists with coronary artery disease (CAD) and/or risk factors for atherosclerosis. Because the silent or documented atherosclerosis or vascular risk factors are very frequent, the possibility of endothelial dysfunction in ED patients is expected to be increased. Our aim was to evaluate the endothelial functions in patients with vasculogenic ED with vascular risk factors and compare them with age-matched non-ED patients or healthy controls. DESIGN: We studied 36 patients with presumed vasculogenic ED, 39 age-matched patients with similar risk factors without ED and 25 age-matched healthy controls without ED, known cardiovascular disease or risk factors. Erectile function was evaluated by the International Index of Erectile Dysfunction (IIEF) scores. Brachial artery flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD) were measured. RESULTS: Baseline demographics were similar except the IIEF score and duration of diabetes in patients with ED. Brachial artery FMD and NMD were significantly reduced in patients with ED (3.2+/-3. vs. 6+/-4, p<0.0001 for FMD, 12.2+/-6 vs. 15.4+/-6 p=0.032 for NMD). In patients with similar risk factors but without ED, FMD was significantly lower but NMD were not different compared with healthy controls (6+/-4 vs. 10.2+/-3, p<0.0001 for FMD and 15.4+/-8 vs. 16.4+/-6, p=0.81). IIEF scores were weakly correlated with FMD (r=0.25, p=0.028) in patients with ED. There were significant correlations between FMD and NMD in patients with ED (r=0.46, p=0.05) and with risk factors (r=0.72, p<0.0001) but not in healthy controls (r=0.54, p=0.792). Vasculogenic ED patients have more markedly impaired endothelial and smooth muscle functions compared with patients with similar risk factors but no ED.     

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.     

Enhanced endothelium-dependent microvascular responses in patients with Wegener's granulomatosis

OBJECTIVE: To assess endothelial cell (EC) function of the cutaneous microcirculation in patients with Wegener's granulomatosis (WG) and to relate EC function to EC activation and presence of atherosclerosis. METHODS: We studied 28 WG patients with inactive disease and 28 age and sex matched controls. Common carotid intima-media thickness (IMT), as a measure of atherosclerosis, was determined by ultrasonography. EC function of microcirculation in the fingers was assessed using laser Doppler fluxmetry in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), which are endothelium-dependent and endothelium-independent vasodilators, respectively. In addition to vascular responses, traditional cardiovascular risk factors were recorded, and EC activation was assessed by serological measures. RESULTS: WG patients had increased IMT compared to controls (0.71 mm vs 0.66 mm; p < 0.05). In WG patients IMT correlated positively with age and body mass index (BMI), and negatively with duration of prednisolone use and cumulative prednisolone dose. Levels of von Willebrand factor and C-reactive protein were increased in patients with WG (p < 0.05). ACh-induced but not SNP-induced vasodilatation was enhanced in WG patients compared to controls. When patients and controls with increased IMT were excluded, the difference in relative response to ACh became significant (median 567% vs 334%; p = 0.007). The response to ACh correlated negatively with age. CONCLUSION: We confirmed that WG patients have accelerated atherosclerosis as measured by IMT. EC activation and disturbed microvascular endothelium-dependent vasodilatation were present in the microcirculation of WG patients with inactive disease and without signs of atherosclerosis, indicating and contributing to a proatherogenic state.     

Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease

OBJECTIVES: The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events. BACKGROUND: Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown. METHODS: We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery. RESULTS: Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 +/- 2.8%) compared with those without an event (7.0 +/- 4.9%, p < 0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, independent predictors of events included age (p = 0.003), more invasive surgery (surgery other than carotid endarterectomy, p = 0.02), and impaired brachial-artery endothelial function (p = 0.002). Risk was approximately nine-fold higher in patients with FMD <8.1% (lower two tertiles) compared with those in the upper tertile (odds ratio 9.5; 95% confidence interval 2.3 to 40). CONCLUSIONS: Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk.     

Measurement of flow-mediated dilatation of the brachial artery is affected by local elastic vessel wall properties in high-risk patients

OBJECTIVES: To assess whether the validity of endothelial function measurement by flow-mediated dilatation (FMD) is affected by local brachial artery stiffness (distensibility coefficient; DC) and arterial wall thickness (intima-media thickness, IMT). BACKGROUND: FMD measurement relies on assessment of arterial diameter change. Increased IMT and decreased DC might physically limit dilatation of the brachial artery in spite of healthy endothelium. METHODS: DC, IMT and FMD of the brachial artery were simultaneously measured in 349 patients with advanced atherosclerosis or cardiovascular risk factors. The relations between FMD and age, and FMD and current smoking were regarded as a proxy for the relation between FMD and true endothelial function. RESULTS: The relations between FMD and age, and FMD and smoking, were significantly modified by brachial artery DC. No modification was found for IMT. The interaction terms were statistically significant (p=0.03 and 0.04, respectively). The relation between FMD and age, and FMD and smoking was progressively more pronounced in patients with more elastic arteries. CONCLUSION: The results of our study indicate that increased arterial stiffness may interfere with valid measurement of FMD and that patients with stiff arteries may be considered for exclusion from analyses involving FMD to ensure its validity.     

Carotid intima-media thickness,arterial stiffness and risk of cardiovascular disease: current evidence

AIMS: Over recent decades the interest in cardiovascular epidemiology has broadened from studies on causes and consequences of elevated cardiovascular risk factors to include research on causes and consequences of atherosclerosis and associated arterial wall abnormalities. One of the underlying reasons was that established cardiovascular risk factors were insufficiently accurate in identifying those individuals who will suffer from cardiovascular disease in the future and measures of subclinical atherosclerosis may enhance the precision of these predictions and thus enable better-tailored medical care to be provided. The usefulness of measuring subclinical atherosclerosis is conditional on evidence that presence of subclinical atherosclerosis confers an increased risk of cardiovascular disease and that favourable changes in subclinical atherosclerosis parallel reductions in risk. We aimed at providing an overview of epidemiological data on carotid intima-media thickness (CIMT) and arterial stiffness measurements and their relation to risk of cardiovascular disease. METHODS: We reviewed the published epidemiological data. RESULTS AND CONCLUSION: CIMT is a good indicator of cardiovascular risk and provides a graded measure of vascular damage: no clear CIMT level above which the cardiovascular risk appears to increase considerably The evidence for arterial stiffness, assessed as carotid distensibility or aortic pulse wave velocity, as an indicator for risk of cardiovascular disease is restricted to subjects with either hypertension or end-stage renal disease or based on small studies in renal transplant patients and elderly. Evidence to indicate that information on carotid intima-media thickness or arterial stiffness, additional to established cardiovascular risk factors, helps to distinguish subjects into those with a high and those with a low absolute risk of cardiovascular disease is limited, but needed. Also, information on the direct comparison of both arterial stiffness measures in their ability to predict cardiovascular disease is needed.     

Intima Media Thickness and Endothelial Function in Chronic Hemodialysis Patients

The purpose of our study was to evaluate the intima‐media thickness (IMT) of the carotid and brachial arteries, flow‐mediated dilatation (FMD), and nitroglycerin‐mediated dilatation (NMD) in diabetic and non‐diabetic hemodialysis patients. We also examined the effects of traditional and other risk factors on carotid and brachial IMT, FMD and NMD in all hemodialysis patients. Fifty‐eight adult hemodialysis patients, 14 of whom had diabetes, were studied. They had been on hemodialysis for 1–340 months. Using B‐mode ultrasonography, we measured the carotid and brachial IMT, FMD and NMD, and correlated the values with cardiovascular risk factors. FMD and NMD were significantly lower in diabetic patients (FMD 4.01 ± 0.99 vs. 6.69 ± 2.37 mm; NMD 9.1 ± 1.95 vs. 11.23 ± 2.86 mm), while no such differences were found between the two groups with respect to carotid or brachial IMT. In all patients with respect to age a positive correlation was found with carotid and brachial IMT, and a negative one with FMD and NMD. With respect to hypertension as well as diabetes, a negative correlation was found with FMD and NMD. Age is the most important factor that significantly affected all studied markers of atherosclerosis in hemodialysis patients. The endothelial and smooth vascular functions are significantly impaired in diabetic and hypertensive hemodialysis patients, and hypertension is shown to be an independent risk factor for smooth vascular dysfunction in hemodialysis patients. According to our results, intensive antihypertensive treatment is recommended in hypertensive chronic hemodialysis patients.     

心血管疾病危险人群中微量白蛋白尿与颈动脉粥样硬化及外周动脉疾病的关系

目的评价存在心血管疾病危险因素但无明确心脑血管疾病的患者中,微量白蛋白尿(MA)与颈动脉粥样硬化(AS)及外周动脉疾病(PAD)的关系。方法采用横断面研究,277例住院有心血管疾病危险因素但无明确心脑血管疾病的患者,根据其尿白蛋白/肌酐(UACR)水平分为两组:微量白蛋白尿组(MA组,男:17 mg/g≤UACR≤250 mg/g;女:25 mg/g≤UACR≤355 mg/g)及不伴微量白蛋白尿组(NMA组,男:00.05)。结论心血管疾病高危患者中,伴MA者颈总动脉AS和PAD的危险性均增加,MA与颈总动脉AS的关系较与PAD的关系更加明显。     

Cardiovascular function in normotensive offspring of persons with essential hypertension and black race

Prior investigations have shown impaired endothelial function in hypertensive blacks when compared with whites. It is not clear, however, whether the difference in vascular responsiveness predates or follows the development of hypertension. Thirty-nine young black adults with a family history of essential hypertension and 41 control participants were studied for brachial artery reactivity and carotid intima-media thickness via ultrasonography, cardiac muscle mass and diastolic function by echocardiography, and biochemical analysis. There was no significant difference in brachial artery reactivity between the study groups, although women had greater reactivity than men (P=.05). Carotid intima-media thickness, left ventricular geometry, and biomarkers were equivalent between the study groups (P=not significant). Vascular imaging and biomarkers were unable to identify early evidence of endothelial dysfunction in offspring of African Americans with essential hypertension. These same studies demonstrated some early changes in vascular function based on sex.     

Angiotensin-converting enzyme gene insertion/deletion polymorphism and carotid artery wall thickness in patients with peripheral arterial occlusive disease.

BACKGROUND: It has been suggested that the deletion polymorphism of the angiotensin converting enzyme (ACE) gene is linked to a high risk of cardiovascular disease. The relationship between the insertion/deletion (I/D) polymorphism of the ACE gene and the carotid intima-media thickness in patients with peripheral arterial occlusive disease is unknown. We tested the hypothesis that the early progression of atherosclerosis in the extracranial carotid arteries in patients with peripheral arterial disease is associated with a genetic predisposition. METHODS: This prospective trial included 98 patients who only had manifestations of arteriosclerotic disease in peripheral arterial vascular regions of the lower extremities (stable stage II PAOD). Maximal common carotid intima-media thickness (mIMT) was measured using high resolution B-mode ultrasonography. Determinations of ACE gene polymorphism were made using a polymerase chain reaction technique. Multivariate regression analysis was performed to assess the influence of ACE genotypes, ACE activity and vascular risk factors on intima-media thickness. RESULTS: There was no significant association between intima-media thickness and ACE gene polymorphism. History of symptomatic peripheral arterial disease without local or systemic progression exists in subjects with the II-genotype significantly longer than in subjects with the DD genotype (p=0.01). With the presence of an II-genotype, there was also a tendency towards a thinner intima-media thickness. We found significant correlations between intima-media thickness and age (p<0.0001), fasting serum insulin (p=0.001), and lipoprotein (a) (p=0.008). CONCLUSIONS: In the present study involving patients with stage II peripheral arterial occlusive disease, ACE gene polymorphism could not be identified as a determining marker for the development of intima-media thickening in the common carotid artery. However, it can be assumed that there is a reduced risk for the systemic progression of atherosclerosis in patients with the II genotype.     

Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients.

Hypertension is a risk factor for coronary atherosclerosis possibly via an adverse effect on the vascular endothelium. Endothelium-mediated relaxation is impaired in animal models of hypertension. However, the effects of hypertension on human coronary artery endothelial cell function are unknown. To test whether endothelium-mediated relaxation is impaired in the coronary arteries of patients with hypertension, we studied 14 patients with essential hypertension requiring therapy and 15 nonhypertensive control patients undergoing cardiac catheterization. All had angiographically normal, smooth-appearing coronary arteries. Patients were matched for age and other coronary atherosclerosis risk factors. To assess endothelial cell function, the endothelium-dependent vasodilator acetylcholine (ACh, 0.01, 0.1, and 1.0 microM) and the endothelium-independent vasodilator nitroglycerin (40 micrograms) were selectively infused into the left anterior descending or circumflex coronary artery. Diameter change (expressed as percent) was assessed using quantitative angiography. There was a marked vasoconstrictor response to serial doses of ACh in hypertensive patients (-7%, -21%, and -27%) compared with control patients (-4%, -5%, and -7%) (p less than 0.02). The vasodilator response to nitroglycerin was preserved in hypertensive patients (+29%) and control patients (+25%) (p = NS), suggesting that endothelial cell dysfunction accounted for the differences in response to ACh. Thus, patients with hypertension have an accentuated coronary vasoconstrictor response to ACh, suggesting that endothelium-mediated regulation of coronary vascular tone is impaired by essential hypertension. This may reflect more generalized coronary endothelial changes contributing to the pathogenesis of atherosclerosis as well as hypertension.