Mean Intima-media Thickness Values Research Articles

Impact of multiple cardiovascular risk factors on femoral artery intima-media thickness in asymptomatic young adults (the Bogalusa Heart Study)

Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. Although risk factors for coronary artery disease are also associated with increased IMT, especially as measured in carotid arteries, there is a paucity of information with respect to the femoral artery in this regard in the asymptomatic, younger adult population. This study examined the impact of multiple risk factors on the common femoral artery IMT as measured by B-mode ultrasonography in 1,080 black and white subjects aged 24 to 43 years (71% white and 43% men) enrolled in the Bogalusa Heart Study. Femoral IMT showed gender difference (men more than women, p = 0.001), but no racial difference. In a multivariate model, systolic blood pressure, age, male gender, cigarette smoking, and total cholesterol/high-density lipoprotein cholesterol ratios related independently, in that order, to IMT. Mean IMT increased with an increasing number of risk factors defined as values above the age-, race-, and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, and insulin along with smoking status (p for trend = 0.003), with respective mean IMT values of 0.66, 0.69, 0.73, and 0.79 mm for 0, 1 to 2, 3, and 4 to 5 risk factors. The odds ratio for patients with >/=3 risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (p = 0.01). The observed adverse trend of increasing femoral IMT with an increasing number of risk factors in free-living, asymptomatic young subjects underscores the need for multiple risk factors profiling in early life. Further, ultrasonography of the femoral artery in conjunction with multiple risk factor profiling can be helpful in risk stratification.

Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms and their association with carotid artery intima-media thickness in the Finnish population : The Cardiovascular Risk in Young Finns Study

Apolipoprotein A-I/C-III/A-IV (apoA-I/C-III/A-IV) SstI and apolipoprotein B (apoB) XbaI polymorphisms have been shown to affect serum low-density lipoprotein (LDL) cholesterol concentrations in a sample of Finnish children. We studied whether these polymorphism are associated with carotid artery intima-media thickness (IMT), a marker of pre-clinical atherosclerosis, measured in the same subjects during their adulthood. A random sub-sample of 214 individuals from the ‘Cardiovascular Risk in Young Finns’ study, for whom genotypes, cardiovascular risk factor data and carotid artery IMT measured in 2001 were available, were studied. Mean carotid IMT values increased according to the apoA-I/C-III/A-IV SstI genotype groups in the order of S1S1 (0.58 ± 0.08 mm), S1S2 (0.61 ± 0.08 mm), and S2S2 (0.70 ± 0.16 mm, p = 0.02, ANOVA). In multiple linear regression analysis after adjusting for age, sex and body mass index the mean IMT thickness among the S2 allele carriers was higher ( p = 0.02) compared to non-carriers. In logistic regression analysis the frequency of S2 allele carriers was higher among the high IMT group compared to the low IMT group (OR = 4.02, CI: 1.68–9.61, p = 0.002). No significant association between apoB XbaI polymorphism and carotid IMT was found. However, serum total and LDL cholesterol and apoB concentrations were significantly different among apoB genotype groups ( p < 0.001 for all traits). The apoA-I/C-III/A-IV SstI polymorphism is associated with carotid IMT in young Finns.

Genetic and environmental contributions to carotid intima-media thickness and obesity phenotypes in the Northern Manhattan Family Study.

Both carotid intima-media thickness (IMT) and obesity are independent determinants of stroke and cardiovascular disease. The prevalence of obesity is higher in Hispanics. The genetic basis of IMT and obesity has not been well-characterized in Caribbean Hispanics. The purpose of this study was to examine the genetic and environmental contributions to IMT and obesity in this population. The data included 440 subjects from 77 Caribbean Hispanic families. Mean IMT and maximum IMT were measured in the internal carotid artery, common carotid artery, and carotid bifurcation. The total IMT was calculated as the mean value of IMT at all segments. Obesity phenotypes included body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), and skin-fold thickness. Variance component methods were used to estimate age-adjusted and sex-adjusted heritability. Bivariate analyses were conducted to test for genetic and environmental correlations between IMT and obesity. Heritabilities for IMT ranged from 9% to 40%, with the highest for total maximum IMT and lowest for internal carotid artery maximum IMT. Heritabilities for BMI, waist circumference, WHR, and skin-fold thickness were 44%, 47%, 5%, and 36%, respectively. There were significant genetic, but not environmental, correlations between IMT and BMI, waist circumference, and skin-fold thickness. There were no genetic or environmental correlations between IMT and WHR. We found a substantial genetic contribution to IMT, BMI, waist circumference, and skin-fold thickness. Obesity and IMT may share common genetic factors. Future gene mapping studies are warranted to identify genes predisposing to IMT and obesity in this population.

Association of carotid intima-media thickness and arterial stiffness with diabetic retinopathy: the Chennai Urban Rural Epidemiology Study (CURES-2).

The aim of this study was to assess the association of intima-media thickness (IMT) and arterial stiffness with diabetic retinopathy in an Asian-Indian population that has very high prevalence rates of diabetes and coronary artery disease. The study was conducted on 600 type 2 diabetic subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), which is an ongoing population-based study of a representative population of Chennai. When present, retinopathy was graded according to a modified Early Treatment Diabetic Retinopathy Study grading system. IMT was determined using high-resolution B-mode ultrasonography. Arterial stiffness was measured by assessing the augmentation index (AI) using the Sphygmocor apparatus. Retinopathy was diagnosed in 116 of 590 (19.6%) subjects in whom retinal photography was possible. Mean values of IMT (0.93 +/- 0.36 vs. 0.85 +/- 0.21 mm, P = 0.001) and AI (27.9 +/- 8.9 vs. 25.8 +/- 9.6%, P = 0.031) were significantly higher among diabetic subjects with retinopathy compared with those without. Both IMT (P = 0.024) and AI (P = 0.050) showed a significant association to diabetic retinopathy, even after adjusting for age, duration of diabetes, HbA(1c), serum cholesterol, serum triglycerides, and microalbuminuria. Diabetic retinopathy is associated with IMT and AI, suggesting that common pathogenic mechanisms might predispose to diabetic micro- and macroangiopathy.

Lack of concordance between plasma markers of cardiovascular risk and intima-media thickness in patients with type 2 diabetes.

Endothelial dysfunction, oxidative stress and systemic inflammation play an important role in the enhanced cardiovascular risk in diabetes. Carotid intima-media thickness (IMT), a widely accepted marker of subclinical atherosclerosis, is known to be increased in patients with type 2 diabetes. The relationships between plasma markers of cardiac risk and carotid IMT are not well known. We therefore studied a group of patients with type 2 diabetes to evaluate the relationships between plasma markers of cardiac risk and carotid IMT. We measured carotid IMT and the levels of soluble endothelial adhesion molecules [sE-selectin, intercellular cell adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1)], C-reactive protein (CRP) and 8-isoprostane in 40 patients with type 2 diabetes without clinical macrovascular complications (HbA1c<10%, duration of diabetes<12 years) and 25 healthy subjects. We then examined the correlations between these plasma markers, carotid IMT and various clinical and biochemical parameters. Diabetic patients had higher plasma sE-selectin (p=0.03), sICAM-1 (p=0.05), CRP (p=0.047) and 8-isoprostane (p=0.001) concentrations than control subjects. Mean IMT values were identical (0.63 +/- 0.02 mm) in diabetic (range, 0.40-0.92 mm) and healthy subjects (range, 0.45-0.85 mm). In diabetic patients, stepwise multivariate analysis showed that HbA1c and plasma glucose were independent predictors of sE-selectin (r2=0.19 and r2=0.17, p<0.01, respectively), whereas waist circumference and body mass index (BMI) were predictors of sICAM-1 (r2=0.27, p=0.001 and r2=0.22, p=0.002, respectively). Waist circumference was the only predictor of CRP (r2=0.2, p<0.01), and systolic blood pressure was the only predictor of 8-isoprostane (r2=0.19, p=0.006). In control subjects, similar analysis showed that plasma glucose and waist circumference were predictors of sE-selectin and sICAM-1, respectively (r2=0.2, p<0.05). These results indicate that some well-controlled type 2 diabetic patients free of clinical macrovascular complications have elevated plasma markers of cardiovascular risk without having increased IMT. The elevation of plasma markers of endothelial cell activation (sE-selectin and s-ICAM-1) or inflammation (CRP) and oxidative stress (8-isoprostane) in diabetics vs. controls is distinct from and cannot be explained simply by differences in the burden of atherosclerosis as assessed by carotid IMT.

Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X.

Endothelial dysfunction and subangiographic atheroma have been reported in patients with cardiac syndrome X (CSX) but little is known regarding chronic inflammation and reduced arterial distensibility as pathogenic mechanisms. We assessed whether markers of inflammation and arterial distensibility differ in CSX patients compared to control subjects. We studied 30 consecutive CSX patients (mean age 57+/-6 years, 25 women) and 30 healthy controls (mean age 54+/-8 years, 25 women). High sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with CSX compared to controls (2.6 [1.7-4.5] vs 1.5[0.7-2.7] mg/l, P=0.02). Hs-CRP levels correlated with carotid intima-media thickness (IMT) (Spearman's rho=0.51; P=0.013). CSX patients also had significantly increased mean IMT values than controls (P<0.0001). Arterial stiffness and elastic modulus were also significantly increased in CSX patients compared to control subjects (P=0.04 and P=0.04, respectively). Distensibility tended to be lower in CSX patients than controls although this difference did not reach statistical significance. This study showed for the first time that compared to control subjects, patients with CSX have higher hs-CRP serum levels, increased mean common carotid artery IMT and increased arterial stiffness. The role of these abnormalities in the pathogenesis of CSX deserves investigation.

Combined genotypes of ACE and NADPH oxidase p22phox associated with somatic mutation of mtDNA and carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus

Background: We previously reported that the carotid artery intima-media thickness (IMT) increased with age and that patients with type 2 diabetes mellitus (DM) had a significantly larger IMT than did age-matched nondiabetic subjects with normal glucose tolerance. Although the exact mechanism behind the increase in IMT in diabetic patients has not been determined, data obtained from in vivo and in vitro studies suggest that hyperglycemia-induced oxidative stress may lead to atherogenesis. Objective: The aim of this single-center study was to determine whether long-term oxidative stress and the carotid IMT are influenced by differences of the angiotensin-converting enzyme insertion/deletion ( ACE I/D) and NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) oxidase p22phox C242T genotypes. Methods: Eligible subjects were Japanese patients with type 2 DM. Polymorphism of the ACE I/D and p22phox gene was investigated using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively. The rate of an acquired mutation of mitochondrial DNA—that is, A-to-G substitution at position 3243 (mtDNA A3243G)—was determined by real-time PCR. As a marker of early atherosclerosis, the carotid artery IMT was measured using high-resolution B-mode ultrasonography. Results: A total of 262 Japanese patients (173 men, 89 women; mean [SEM] age, 58 [0.6] years [range, 18–80 years]) were recruited and enrolled for study. An ACE D- positive ( DD or DI) and p22phox 242T-negative genotype ( CC) was associated with a significantly higher mtDNA A3243G mutation rate than the other 3 possible genotypes (0.0219% [0.0028%] vs 0.0097% [0.0012%]; P < 0.05). This genotype also had higher maximum and mean IMT values than the other genotypes (1.13 [0.048] mm vs 0.99 [0.03] mm and 1.01 [0.036] mm vs 0.92 [0.023] mm; P < 0.05). These parameters were similar among the other 3 genotypes. Conclusion: In this study, the ACE D- positive and p22phox 242T-negative genotype showed higher rates of somatic mtDNA mutation (mtDNA A3243G) and higher carotid mean and maximum IMT levels.

Arterial Intima-Media Thickness and its Relationship with Cardiovascular Disease and Atherosclerosis: A Possible Contribution of Medium-Sized Arteries

The intima-media thickness (IMT) of the arterial wall, measured by B-mode ultrasonography, has been related to cardiovascular disease and atherosclerosis in many studies, most of which have considered carotid and common femoral arteries. No study has related the IMT of medium-sized arteries (e.g. brachial) to the atherosclerotic process. The aim of this study was to evaluate whether more peripheral arteries (e.g. brachial, superficial femoral and popliteal) represent a good model in studies of arterial wall IMT, as well as carotid artery. Twenty-six male patients with demonstrated coronary artery disease (median age 63 yrs; range 41-70) and twenty-four male controls (median age 62 yrs; range 53-74) were studied. The far-wall IMT of the common carotid, brachial, superficial femoral and popliteal arteries was measured by high-resolution B-mode ultrasonography. Its relationship with ischemic cardiovascular disease and the presence of atherosclerotic plaques in all the arteries was also evaluated. Mean IMT values were higher in patients than controls, more so in superficial femoral artery (IMT difference 0.08 mm [95% confidence interval 0.02 - 0.14]) and popliteal artery (0.08 [0.01-0.15]) than in common carotid artery (0.02 [-0.07-0.11]) or brachial artery (0.01[-0.01-0.03]). The difference did not change after adjustment for age. The prevalence of plaques was consistently higher in patients than controls, except for brachial artery, in which no plaque was found either in patients and controls. In all the arteries except brachial we found an association between increase in IMT and number of plaques. Age was strongly related to the presence of plaques in the carotid artery, and less markedly in superficial femoral and popliteal arteries. The brachial artery does not seem a good model to study atherosclerosis by ultrasound measurements of arterial IMT, whereas superficial femoral and popliteal arteries might be chosen for these studies besides carotid artery.

Association of C-reactive protein with markers of prevalent atherosclerotic disease

Recent prospective studies have demonstrated that elevated C-reactive protein (CRP) is a marker of increased risk of atherothrombotic clinical events. We examined in a large, cross-sectional family-based study (n = 875 men, 948 women) whether serum CRP was associated with prevalent coronary heart disease (CHD), the ankle/brachial blood pressure index, or carotid intima-media thickness, an indicator of subclinical atherosclerosis as assessed by B-mode ultrasound. CRP was associated with many other cardiovascular risk factors, particularly markers of obesity and insulin resistance, markers of inflammation and acute phase reaction, and hormone replacement therapy. Adjusted for age and family type, there was a weak positive association of CRP with carotid intima-media thickness in both genders and with prevalent CHD in women. However, adjustment for other risk factors completely eliminated the associations. For example, among women, the risk factor-adjusted mean values of intima-media thickness across quartiles of CRP were 0.76, 0.74, 0.75, and 0.76 mm (p >0.5). In men there was a weak inverse association between CRP and ankle/brachial blood pressure index, independent of other risk factors, but no such association in women. Our findings indicate that CRP is not strongly and independently associated with prevalent atherosclerosis. Because CRP has been associated with clinical events, it could be that elevated CRP may be a stronger marker of thrombotic risk than of the degree of atherosclerosis.

Duration of menopause and behavior of malondialdehyde, lipids, lipoproteins and carotid wall artery intima-media thickness

Aim: our study assessed whether minor or major hormonal deficiency influenced oxidative status and vascular wall structure in menopausal women. Methods: the study series was made up of 62 non hypertensive non diabetic menopausal women (mean age 52.3±4.7 years) divided into two groups depending on duration of menopause (group 1 duration 0–5 years; group 2 duration over 5 years). Total cholesterol (TC), LDL cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), malondialdehyde (MDA) and common carotid artery wall intima-media thickness (IMT) were determined in the entire series. Results: mean TC, LDL-C, TG, MDA and IMT values were higher in group 2 than group 1. The intergroup difference between MDA ( P<0.007) and IMT values ( P<0.006) values was statistically significant. Conclusions: the study revealed a close temporal correlation between plasma oxidative stress and carotid wall IMT, jeopardizes vascular wall status as menopause proceeds.

Apolipoprotein E polymorphism and carotid artery intima-media thickness in a random sample of middle-aged men

Genetic polymorphism of apolipoprotein E (apoE) is an important factor in the development of coronary artery disease but the results concerning apoE genotype and carotid artery atherosclerosis remain controversial. We investigated a random sample of 189 Finnish middle aged men (mean age 54 years, range 50–59) to assess the role of apoE in the process of carotid atherosclerosis. Intima-media thickness (IMT) of the carotid artery wall was measured at three standardised segments (common carotid artery, bifurcation and internal carotid artery) by B-mode ultrasonography. Overall mean IMT value was also calculated. The carriers of E3/2 ( n=20) genotype had significantly lower ( P<0.01) total cholesterol and LDL cholesterol concentrations than carriers of E3/3 genotype ( n=109) or the E4 allele ( n=60). ApoE polymorphism was associated with common carotid artery IMT ( P=0.034) when adjusted for age and body-mass index (model 1). The carriers of E3/2 had on average 9% (95% CI 0.8–16%, P=0.028) lower common carotid IMT values than the carriers of E3/3. After further adjustment with LDL and HDL cholesterol, systolic blood pressure, lipoprotein (a), apolipoprotein B and pack-years of smoking (model 2) the association was not statistically significant. The overall mean IMT varied significantly with apoE genotype ( P=0.03 for model 1 and P=0.07 for model 2), and it was also lowest in the carriers of E3/2 genotype. This suggests that apoE E3/2 genotype is a protective factor in the development of carotid artery atherosclerosis in randomly selected middle-aged men. The favourable effect might be mediated at least partly by the lowering effect of E3/2 genotype on serum cholesterol.