Mean Intima-media Thickness Research Articles

Genetic and Acquired Inflammatory Conditions Are Synergistically Associated With Early Carotid Atherosclerosis

If chronic inflammation plays a causal role in atherogenesis, individuals with proinflammatory gene variants would be expected to develop more atherosclerosis. We recently found a synergistic association between 3 functional proinflammatory gene polymorphisms/haplotypes and smoking on carotid intima-media thickness (IMT). We replicated this finding in a second large population and extended the analysis by inclusion of other inflammatory conditions (chronic infection and obesity/abnormal glucose tolerance). Common carotid and femoral artery IMT was determined in the Bruneck Study population (n=810). Proinflammatory variants were determined in 3 genes (IL-6 [-174C, -572G, -597A haplotype], IL-1-receptor antagonist [VNTR *2], and endotoxin receptor CD-14 [-159C]). There was a significant relationship between gene-variant score and carotid IMT: age- and sex-adjusted mean IMT in subjects with 0, 1, and >or=2 gene variants was 936, 987 and 1047 microm, respectively (P=0.001), and synergistic effects of gene-variant score and smoking on IMT measurements (P=0.040). Analogous findings were obtained for obesity/abnormal glucose tolerance and chronic infection. Interactive effects of gene-variant score and a risk factor score composed of the acquired inflammatory conditions were highly significant (P<0.001 each). Results were similar for femoral artery IMT. These results provide support for a causal role of inflammation in carotid atherosclerosis, and emphasize the importance of gene-gene and gene-environment interactions in this pathogenic pathway. This may help to explain the substantial variability of disease expression in subjects with proinflammatory risk factors such as smoking, diabetes and chronic infection.

Effects of lifestyle modification on metabolic parameters and carotid intima-media thickness in patients with type 2 diabetes mellitus

The aim of this study was to examine the effects of a 6-month intensive lifestyle modification intervention on metabolic parameters and carotid intima-media thickness (IMT) in patients with type 2 diabetes mellitus. Fifty-eight subjects with type 2 diabetes mellitus were randomly assigned to the intervention group or the control group. The subjects in the intervention group participated in a 16-week intensive lifestyle modification program and subsequent monthly meetings during the 6-month study period. Control subjects received basic dietary education and usual care. Anthropometric data, metabolic parameters, and carotid IMT were examined before the intervention and after 6 months. Lifestyle modification intervention group patients showed a significant reduction in HbA 1c (−1.0% ± 1.3% vs +0.1% ± 1.2%, P = .002), fasting blood glucose (−1.6 ± 1.5 vs +0.3 ± 2.5 mmol/L, P = .001), and 2-hour postprandial plasma glucose (−2.1 ± 2.5 vs +0.8 ± 4.4 mmol/L, P = .003) compared with control patients after 6 months. Body weight (−2.0 ± 2.6 vs +0.2 ± 1.7 kg, P = .001), body mass index (−0.8 ± 1.0 vs 0.0 ± 0.8 kg/m 2, P = .003), and systolic blood pressure (−8.2 ± 15.9 vs +0.4 ± 14.1 mm Hg, P = .041) were significantly decreased in the intervention group. A significantly reduced carotid mean IMT progression was seen in the intervention group after 6 months (−0.040 ± 0.136 vs +0.083 ± 0.167 mm, P = .007). Changes in HbA 1c ( r = 0.34, P = .028), fasting plasma glucose ( r = 0.31, P = .045), and 2-hour postprandial plasma glucose ( r = 0.37, P = .015) correlated with the mean carotid IMT change after adjustment for age and sex. In conclusion, a 6-month intensive lifestyle modification intervention in patients with type 2 diabetes mellitus resulted in improved glycemic control and decreased progression of carotid IMT.

Relationship of the metabolic syndrome to carotid ultrasound traits

BackgroundThe metabolic syndrome is associated with increased vascular disease risk. We evaluated two carotid ultrasound measurements, namely intima media thickness and total plaque volume, in a Canadian Oji-Cree population with a high metabolic syndrome prevalence rate.MethodsAs part of the Sandy Lake Complications Prevalence and Risk Factor Study, 166 Oji-Cree subjects (baseline metabolic syndrome prevalence, 44.0%, according to the National Cholesterol Education Program Adult Treatment Panel III guidelines) were examined using a high-resolution duplex ultrasound scanner.ResultsImage analysis showed that mean intima media thickness was elevated in subjects with the metabolic syndrome (818 ± 18 vs 746 ± 20 μm), as was total plaque volume (125 ± 26 vs 77.3 ± 17.0 mm3). However, after adjustment for age and sex, the differences were significant only for intima media thickness (P = 0.039). Furthermore, a significant trend towards increased intima media thickness was observed with increasing numbers of metabolic syndrome components: mean intima media thickness was highest among individuals with all five metabolic syndrome components compared to those with none (866 ± 55 vs 619 ± 23 μm, P = 0.0014). A similar, but non-significant trend was observed for total plaque volume.ConclusionThis is the first study of the relationship between the metabolic syndrome and two distinct carotid ultrasound traits measured in the same individuals. The results suggest that standard intima media thickness measurement shows a more consistent and stronger association with the metabolic syndrome than does total plaque volume.

Carotid Black Blood MRI Burden of Atherosclerotic Disease Assessment Correlates with Ultrasound Intima-Media Thickness

The aim of this study was to correlate carotid black blood MRI based measurements with those obtained by ultrasound intima-media thickness (IMT). Seventeen patients with intermediate to high Framingham cardiovascular risk score underwent both carotid ultrasound and rapid extended coverage double inversion recovery black blood carotid MRI. Overall, there was good correlation between wall area, wall thickness, and plaque index measured by MRI and the IMT measurements obtained from the ultrasound images (max r2 = 0.72, p < 0.05). Patients with mean IMT > or = 1.2 mm had significantly higher values of wall area, plaque index and wall thickness compared to patients with mean IMT < 1.2 mm. Vessel wall measurements assessed by black-blood MRI may be potentially used clinically to evaluate plaque progression and regression.

Po‐Thur Eve General‐24: Non‐Invasive Imaging Phenotypes of Carotid Atherosclerosis in Subjects: MRI, B‐mode and 3D Ultrasound Measurements

Atherosclerosis is a chronic inflammatory disease, characterized by the accumulation of lipids and fibrous elements within the inner‐most layer of the artery wall. Vulnerable atherosclerotic plaques may eventually rupture, resulting in emboli that can obstruct blood flow and result in stroke or myocardial infarction. Direct measurements of atherosclerosis include non‐invasive imaging phenotypes such as MRI and 3DUS derived plaque and wall volume measurements and B‐mode US measurements of the intima media thickness (IMT). Here we report the first comparison of IMT with 3D Ultrasound and MRI‐derived atherosclerosis phenotypes measured in five subjects with moderate carotid atherosclerosis. Five research subjects with carotid plaque area ⩾ 0.5 cm2 were studied and all subjects were undergoing treatment for hyperlipidemia. Mean age was 66 yrs with no significant difference between males and females. Subjects underwent MRI, 3DUS and 2D B‐mode US of the left and right carotid arteries. A single observer carried out 3DUS vessel wall volume measurements (VWV) in 10 subject images at both time points, a second observer measured MRI vessel wall volume; a third observer measured IMT. Both 3DUS VWV and MRI VWV measurements were repeated five times to determine intra‐observer variability and variability between time points. At baseline 3DUS and MRI VWV measurements were not significantly different. No significant differences was observed for mean 3DUS VWV and MRI VWV at test and retest. No significant difference between mean IMT at test and retest was found. IMT measurements had the highest intra‐class correlation coefficients and the lowest coefficient of variation values.

Anti-inflammatory cytokines in subclinical carotid atherosclerosis

Some studies have shown correlations between selected proinflammatory factors and carotid atherosclerosis. It has not been established whether anti-inflammatory cytokines are associated with carotid intima-media thickness (IMT), an ultrasound surrogate marker of atherosclerosis. Therefore, the authors studied the relationship between the carotid IMT and serum levels of interleukin (IL)-10 and transforming growth factor-beta1 in 76 subjects. They discovered that lower IL-10 levels were associated with increased mean IMT in common carotid arteries.

Plasma ghrelin concentrations are positively associated with carotid artery atherosclerosis in males

Ghrelin, a peptide hormone from stomach, stimulates food intake and decreases fat utilization. Ghrelin binds to growth hormone secretagogue receptor (GHSR). GHSR density has been shown to be upregulated in atherosclerotic lesions, but the relationship between ghrelin concentration and atherosclerosis has not yet been studied. We, therefore, characterized the association between ghrelin concentration and carotid artery intima-media thickness (IMT) in a population-based cohort of 1024 middle-aged (40-60 years) men and women. Intima-media thickness and the number of atherosclerotic plaques were determined ultrasonographically. Fasting plasma ghrelin concentrations were analysed using RIA-kit (PhoenixPeptide). There was a positive association between mean IMT and ghrelin concentration in the analysis of males before and after adjustments for the traditional risk factors of atherosclerosis [age, systolic blood pressure, LDL cholesterol, body mass index (BMI), and smoking (ancova, P = 0.004 and P = 0.007, respectively)]. However, no such association was found in females (P = 0.985 and P = 0.915). There was no correlation between ghrelin and CRP concentrations or ghrelin and smoking. Ghrelin concentrations and carotid artery atherosclerosis are positively associated in males even after adjustment for the commonly recognized risk factors of atherosclerosis. Experimental and prospective studies are warranted to elucidate the role of ghrelin in atherosclerosis.

Risk factors for atherosclerosis in healthy employees—a multidisciplinary approach

Background The aim of the study was to investigate the prevalence of early atherosclerosis in healthy workers and the relationship between classical, psychological, and immunological risk factors and atherosclerosis, as well as their predictive value. Methods One hundred healthy managers and 50 office workers aged 35–65 were studied. In all subjects, individual, family, and occupational stress/coping risk factors were evaluated, including plasma levels of biochemical (total cholesterol, LDL, HDL, TG, glucose) and inflammatory-immunological (aCL, anti-β 2 GPI, oxLDL, HSP, HSCRP) parameters. Carotid artery intima-media thickness (IMT) and atherosclerotic plaques in carotid arteries were assessed with computer analysis of B-mode ultrasound images. Results In 107 persons (71%) no changes were found in ultrasound images and in 43 individuals (29%) the presence of plaque was shown. The mean IMT value was 0.0618 ± 0.013 mm. Cross-domain analysis showed that core predictors for IMT were age, LDL level, smoking, and occupation (being a manager) ( β = 0.33, 0.30, 0.23, and 0.20, respectively); the core predictors for plaque were age, total cholesterol level, and an occupational stressor home-work balance (Wald = 7, 6.7, and 5.6, respectively). Immunological factors were not independent predictors. Conclusions In atherosclerosis, not only traditional risk factors (age, lipid disorders, and lifestyle) but also occupational stress factors may play a role. Immunological factors do not seem to play a role in the development of atherosclerosis in a population of healthy workers. The interplay between occupational stress and atherosclerotic changes requires further investigation.

Increased Aortic Intima-Media Thickness Is Related to Lipid Profile in Newborns with Intrauterine Growth Restriction

Background and Aim: Low birth-weight is known to be associated with an increase in cardiovascular risk similar to that seen with major environmental risk factors, such as cigarette smoking or hypertension. Much epidemiological evidence has linked low birth-weight with hypertriglyceridaemia. Method: We measured aortic wall thickness by ultrasonography and lipid profile in 40 newborn babies with intrauterine growth restriction and 40 controls. Results: Maximum and mean aortic intima-media thickness were significantly higher in the babies with intrauterine growth retardation (0.58 ± 0.06, 0.52 ± 0.03 mm, respectively) than in controls (0.44 ± 0.05, 0.40 ± 0.03 mm, p < 0.0001, p < 0.0001, respectively), more so after adjustment for birth-weight (maximum intima-media thickness: 0.23 ± 0.03 mm/kg vs. 0.12 ± 0.02 mm/kg, p < 0.0001; mean intima-media thickness: 0.21 ± 0.02 mm/kg vs. 0.11 ± 0.01 mm/kg, p < 0·0001). Serum triglyceride levels were significantly higher in the intrauterine growth retardation group (48.9 ± 14.8 mg/dl) compared with the control group (32.5 ± 9.8 mg/dl, p < 0.0001). The mean body mass index, prepregnancy weight, weight gain during pregnancy, maternal LDL cholesterol level and, height of the mothers were significantly lower in the intrauterine growth retardation group compared with the control group. For maximum aIMT, significant associations included the ponderal index (p = <0.01), length (p = 0.01) and serum triglyceride levels of infants (p = 0.02). Conclusion: Newborn babies with growth restriction have significant maximum aortic thickening with hypertriglyceridaemia, suggesting that prenatal events might predispose to later cardiovascular risk.

Maternal Diet During Pregnancy and Carotid Intima–Media Thickness in Children

Autopsy studies show that intimal lipid accumulations in arteries are often present at birth, suggesting that the prenatal environment plays a role in the pathogenesis of atherosclerosis. In animal models, a restricted or unbalanced maternal diet during gestation can influence susceptibility to atherosclerosis, but the relation in humans between maternal diet during pregnancy and atherogenesis is unknown. We measured carotid intima-media thickness (IMT) in 216 nine-year-old children whose mothers had participated in a study of nutrition during pregnancy. IMT was greater in boys, in children who were heavier, in those with higher systolic blood pressure, and in those who took less exercise. Increased IMT was associated with a lower maternal energy intake in early (P=0.029) or late (P=0.006) pregnancy, after adjustment for these factors. Mean IMT of children whose mothers were in the lowest quarter of the distribution of energy intake in late pregnancy was 0.027 mm (95% confidence interval, 0.004 to 0.049) greater than that of those whose mothers were in the highest quarter of the distribution. Lower maternal energy intake during pregnancy may increase the susceptibility to atherogenesis of the child.

The relation between components of adult height and intimal-medial thickness in middle age: the Atherosclerosis Risk in Communities Study.

The authors aimed to investigate the relation between components of adult height (leg and trunk length) and atherosclerosis in middle age, using data from 12,254 participants (aged 44-65 years) in the Atherosclerosis Risk in Communities (ARIC) Study. Intimal-medial thickness (IMT) as measured by B-mode ultrasound was the outcome, and exposures were trunk and leg lengths as estimated (using sitting height and the difference between sitting and standing height) at the first study examination in 1987-1989. The mean IMT was 0.73 (standard deviation, 0.17) mm. Greater leg length was associated with lower IMT, with the largest difference being for Black men (a 0.045 (95% confidence interval: 0.023, 0.068)-mm lower IMT per 10-cm higher leg length). Greater trunk length was associated with higher IMT, with the largest difference being for White men (a 0.024 (95% confidence interval: 0.005, 0.044)-mm higher IMT per 10-cm higher trunk length). Although the effect sizes were small, leg length was inversely associated with atherosclerosis, consistent with the results of other studies with cardiovascular disease outcomes.

Remnant particles are the major determinant of an increased intima media thickness in patients with familial combined hyperlipidemia (FCH)

Introduction Familial combined hyperlipidemia (FCH) is characterized by several phenotypes, including an atherogenic lipoprotein profile, low grade inflammation, visceral obesity, insulin resistance, and hypertension. In this study, we investigated which of the clinical and biochemical characteristics of FCH patients contributes most to their increased risk of cardiovascular disease, by determining the association of a broad variety cardiovascular risk factors with the intima media thickness (IMT) of the common carotid artery (CCA) in 94 FCH patients and 216 non-affected relatives. Methods All subjects filled out a questionnaire about their smoking and drinking habits, medical history and medication use, and venous blood was drawn in the fasting state after discontinuation of lipid lowering medication (if used). IMT of the far wall and near wall of both CCAs was measured by high-resolution B-mode ultrasonography. Results The mean IMT in FCH patients (adjusted for age and gender) was 33 μm thicker when compared to their non-affected relatives ( p = 0.006). In multivariate analysis, the waist-to-hip ratio, the apoB concentration and the pulse pressure were significant and independent predictors of IMT in both FCH patients and their normolipidemic relatives. The most important independent predictor of IMT in FCH patients however, was the VLDL-c/TG ratio, explaining 32.8% of the variation in age- and gender-adjusted IMT, whereas this ratio was not an independent predictor of IMT at all in their unaffected relatives. Conclusion Abdominal obesity, a higher blood pressure and dyslipidemia characterised by both an increased number of atherogenic particles and the presence of highly atherogenic remnant lipoproteins play an important role in the development of cardiovascular disease in FCH-patients.

The Inverse Association of Elevated Serum Bilirubin Levels with Subclinical Carotid Atherosclerosis

Background: Serum bilirubin is negatively associated with the development of coronary heart disease. In the present study, we have focused on the analysis of intima-media thickness (IMT) of the common carotid artery in hyper- and normobilirubinemic subjects. Methods: The study was performed on 111 men without manifested atherosclerosis. In all subjects, complete biochemical tests were determined along with the examination of IMT by carotid ultrasound. Results: The mean IMT in hyperbilirubinemic subjects as compared with controls was substantially lower (p = 0.017), and hyperbilirubinemic men also had very low age-adjusted prevalence odds ratios for having IMT above the 50th percentiles of controls, even after adjustment for selected vascular risk factors (p = 0.034). Conclusions: In the present study, we demonstrate the inverse relationship between serum bilirubin and IMT in healthy men.

Evidence for an Association Between Type 1 Diabetes and Premature Carotid Atherosclerosis in Childhood

Acute phase proteins have been suggested to be increased in patients with type 1 diabetes. The aim of this study was to evaluate the relationship between serum C-reactive protein (CRP) and intima-media thickness (IMT) and functions of the common carotid artery (CCA) in children and adolescents with type 1 diabetes. Serum CRP levels were measured in 65 children and adolescents with diabetes (33 girls and 32 boys; mean age, 12.7 +/- 3.8 years; range, 7-18; duration of diabetes, 6.9 +/- 3.6 years). Age and diabetes duration, as well as major cardiovascular risk factors including anthropometric and metabolic parameters, were matched between girls and boys. The relations of serum CRP levels to CCA structure and functions were measured by ultrasonography as IMT, cross-sectional compliance, cross-sectional distensibility, diastolic wall stress (DWS), and incremental elastic modulus (IEM). There was no significant difference for serum CRP levels between girls and boys (3.7 +/- 1.3 vs 3.2 +/- 0.4 mg/L; p > 0.05). CRP was positively correlated with IMT (r = 0.49, p = 0.001), IEM (r = 0.24, p = 0.05), DWS (r = 0.58, p < 0.001), and body mass index (BMI) (r = 0.28, p = 0.05). In a multivariate regression model, we included CRP and metabolic and anthropometric parameters such as duration of diabetes, HbA1c, BMI, waist:hip ratio, age, and systolic and diastolic blood pressure as independent variables in the model for CCA structure and functions. CRP emerged as an independent correlation for mean IMT (beta = 0.51, p < 0.001) and DWS (beta = 0.61, p < 0.001). According to our findings, CRP was associated with CCA structure and functions in children and adolescents with type 1 diabetes.

Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes

To investigate the effect of highly purified eicosapentaenoic acid (EPA) on the progression of diabetic macroangiopathy, we performed an open-label randomized prospective trial. A total of 81 Japanese type 2 diabetes were randomly assigned to the EPA (1800 mg/day) treated group or the control group. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were evaluated before and after treatment in both groups. Sixty patients (EPA group, n = 30; control group, n = 30) completed this study. During the study period of 2.1 ± 0.2 years, the mean IMT and max IMT of the EPA treated group showed a significant annual decrease compared with that of the control group (mean IMT, −0.029 ± 0.112 mm versus 0.016 ± 0.109 mm, respectively, P = 0.029; max IMT, −0.084 ± 0.113 mm versus −0.005 ± 0.108 mm, respectively, P = 0.0008). The baPWV was also improved significantly in the EPA treated group compared with the control group (−22.1 ± 127.9 cm/s versus 62.3 ± 223 cm/s, respectively, P = 0.021). Multiple regression analysis showed that the administration of EPA was a significant and independent factor associated with an annual improvement of mean IMT ( R 2 = 0.067). In summary, this is the first demonstration that administration of purified EPA improves the carotid IMT and the baPWV in patients with type 2 diabetes.

High Plasma Resistin Level Is Associated with Enhanced Highly Sensitive C-Reactive Protein and Leukocytes

Resistin is a newly described hormone with a suggested role in insulin resistance. In humans, inflammatory cells seem to be the major source of resistin. The aim of this study was to find out whether plasma resistin concentration associates with carotid artery atherosclerosis and the risk factors of atherosclerosis. Plasma resistin concentrations were measured in 525 Finnish middle-aged subjects among our population-based cohort. Intima-media thickness was measured from the internal carotid artery, the bifurcation enlargement, and the common carotid artery. Among all the subjects, the median resistin concentration was 7.07 ng/ml (interquartile range, 5.82-8.84), women having higher levels than men (P < 0.001) with median values of 7.56 ng/ml (6.18-9.19) and 6.67 ng/ml (5.63-8.31), respectively. Resistin level correlated negatively with mean intima-media thickness, internal carotid artery, and common carotid artery, but the association did not remain significant after adjustments. Plasma resistin concentration was associated positively with leukocytes (P < 0.001), highly sensitive C-reactive protein (P = 0.009), and IGF binding protein 1 (P < 0.001), but not with plasma insulin or glucose levels in analysis of covariance after adjustments for age, sex, and body mass index. The results imply that inflammatory factors are more important in the determination of plasma resistin concentration than plasma insulin or glucose values. Resistin is associated with proatherogenic inflammatory markers but not independently with early atherosclerosis.

Does Hemophilia Protect Against Atherosclerosis? A Case-Control Study

Whether carriers of hemophilia are protected against the development of atherosclerosis is controversial. In a case-control study, the presence of atherosclerosis was assessed and quantified with echo-color Doppler of all explorable arterial districts in 50 carriers of hemophilia and in 50 age-matched control individuals. All participants submitted to echo-color Doppler of carotid and femoral axis, of brachial arteries, and of the abdominal aorta. The presence and grade of atherosclerotic plaques were assessed, as well as the intima-media thickness (IMT). At least one atherosclerotic plaque was found in six cases (12.0%) versus 15 controls (30.0%); referring to the total number of plaques, 30% of them were evaluated in patients affected by decreased coagulation while 70% in subjects with normal levels of FVIII. In all the examined districts, the mean IMT was significantly lower in patients with hemophilia than in controls. Hemophilia protects against asymptomatic atherosclerosis.

Cardiovascular Morbidity and Mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in Chronic Renal Failure: A Multicenter, Randomized, Controlled Trial

The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) aimed to establish whether high-dose folic acid would slow the progression of atherosclerosis and reduce cardiovascular events in patients with chronic renal failure (CRF). Hyperhomocysteinemia is a potential contributor to the high rates of cardiovascular morbidity and mortality in patients with CRF. A total of 315 subjects with CRF, mean age 57 years (range 24 to 79 years) were randomized to 15 mg folic acid daily or placebo and followed for a median of 3.6 years. The primary intima-media thickness (IMT) and clinical end points were: rate of progression of mean maximum carotid IMT and a composite of myocardial infarction (MI), stroke, and cardiovascular death. Secondary end points included all cardiovascular events and change in pulse wave velocity, systemic arterial compliance and augmentation index. Data were analyzed by intention-to-treat. Plasma total homocysteine was reduced by 19% in the folic acid group. There was no significant difference between the treatment groups in rate of change of IMT or any measure of artery function. Seventy-seven events occurred in the folic acid group (14.9 per 100 patient-years) as compared with 86 in the placebo group (16.3 per 100 patient-years). The rates of the primary and secondary clinical end points at five years were not significantly different after adjustment for baseline differences between the groups (adjusted hazard ratio for MI, stroke, and cardiovascular death: 0.98 [95% confidence interval: 0.66 to 1.47]; p = 0.94; for all cardiovascular events: 0.95 [95% confidence interval: 0.69 to 1.30]; p = 0.75). High-dose folic acid does not slow atheroma progression or improve cardiovascular morbidity or mortality in patients with CRF.

Decreased High-Density Lipoprotein (HDL) Particle Size, Preβ-, and Large HDL Subspecies Concentration in Finnish Low-HDL Families

High-density lipoprotein (HDL) cholesterol correlates inversely with the risk of coronary heart disease (CHD). The precise antiatherogenic mechanisms of HDL subspecies are not thoroughly elucidated. We studied the relationship between carotid intima-media thickness (IMT) and HDL subspecies distribution in Finnish families with low HDL cholesterol and premature CHD. Altogether, 148 members of Finnish low-HDL families and 133 healthy control subjects participated in our study. HDL particle size was significantly smaller in affected family members (HDL < or =10th Finnish age-sex specific percentile) compared with unaffected family members and control subjects (9.1+/-0.04 nm versus 9.5+/-0.05 nm, P<0.0001, versus 9.8+/-0.03 nm, P<0.0001 [mean+/-SE]). Large HDL2b particles as well as prebeta-HDL concentration were significantly decreased among the affected family members. Mean IMT was significantly higher in the affected family members than in the control subjects (0.85+/-0.01 mm versus 0.79+/-0.01 mm; P<0.0001). Age, HDL2b, systolic blood pressure, and prebeta-HDL were significant independent determinants of mean IMT. The decreased levels of HDL2b and prebeta-HDL reflect the potentially efflux-deficient HDL subspecies profile in the affected low-HDL family members. Decreased HDL particle size caused by the decrease of plasma concentration of HDL2b and decreased prebeta-HDL levels correlate with increased IMT.

Apolipoprotein E polymorphism and preclinical carotid artery disease in untreated hypertensive men

The apolipoprotein E (apoE) polymorphism was evaluated alone, and in interaction with smoking status, in predicting carotid intima-medial thickness and plaque among 182 untreated, hypertensive, white men (mean age 56+/-8.9 years). After covariate adjustment (age, education, smoking, body mass index, systolic and diastolic blood pressure, glucose, total : high-density lipoprotein), apoE genotype (no [epsilon]4 versus any [epsilon]4) predicted mean ([beta]=-0.139, P=0.023) and maximum ([beta]=-0.138, P=0.028) intima-medial thickness, as well as plaque ([beta]=-0.744; P=0.072). Tests of a genotype-x-smoking interaction were non-significant. Mean intima-medial thickness was greater in men with the 3/3 than [epsilon]4 genotypes (2/4 3/4 4/4), suggesting genetic risk for carotid atherosclerosis may be conferred by the [epsilon]3, rather than the [epsilon]4, allele.