Changes In Carotid Artery Intima-media Thickness Research Articles

Childhood traffic-related air pollution and adverse changes in subclinical atherosclerosis measures from childhood to adulthood

BackgroundChronic exposure to air pollutants is associated with increased risk of cardiovascular disease (CVD) among adults. However, little is known about how air pollution may affect the development of subclinical atherosclerosis in younger populations. Carotid artery intima-media thickness (CIMT) is a measure of subclinical atherosclerosis that provides insight into early CVD pathogenesis.MethodsIn a pilot study of 70 participants from the Southern California Children’s Health Study, we investigated CIMT progression from childhood to adulthood. Using carotid artery ultrasound images obtained at age 10 and follow-up images at age 21–22, we examined associations between childhood ambient and traffic-related air pollutants with changes in CIMT over time and attained adult CIMT using linear mixed-effects models adjusted for potential confounders.Average residential childhood exposures (i.e., birth to time of measurement at 10–11 years) were assigned for regional, ambient pollutants (ozone, nitrogen dioxide, particulate matter, interpolated from regulatory air monitoring data) and traffic-related nitrogen oxides (NOx) by road class (modeled using the CALINE4 line source dispersion model). Traffic density was calculated within a 300-m residential buffer.ResultsFor each 1 standard deviation (SD) increase in childhood traffic-related total NOx exposure, we observed greater yearly rate of change in CIMT from childhood to adulthood (β: 2.17 μm/yr, 95% CI: 0.78–3.56). Increases in annual rate of CIMT change from childhood to adulthood also were observed with freeway NOx exposure (β: 2.24 μm/yr, 95% CI: 0.84–3.63) and traffic density (β: 2.11 μm/yr, 95% CI: 0.79–3.43). Traffic exposures were also related to increases in attained CIMT in early adulthood. No associations of CIMT change or attained level were observed with ambient pollutants.ConclusionsOverall, we observed adverse changes in CIMT over time in relation to childhood traffic-related NOx exposure and traffic density in our study population. While these results must be cautiously interpreted given the limited sample size, the observed associations of traffic measures with CIMT suggest a need for future studies to more fully explore this relationship.

Nattokinase atherothrombotic prevention study: A randomized controlled trial.

Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.

Traffic-related NOx exposure and proximity to freeways are related to adverse changes in subclinical atherosclerosis measures from childhood to adulthood

Background: Chronic exposure to air pollutants is associated with increased risk of cardiovascular disease (CVD) among adults. However, little is known about how air pollution may affect the development of subclinical atherosclerosis in younger populations. Subclinical measures of atherosclerosis, including carotid artery intima-media thickness (CIMT) and arterial stiffness (CAS), may provide insight into early CVD pathogenesis. Methods: In a pilot study of 70 participants from the Southern California Children’s Health Study, we investigated subclinical atherosclerosis progression from childhood to adulthood. Using carotid artery ultrasound images obtained at age 10 and follow-up images from age 21-22, we examined associations between traffic-related pollutants and changes in CIMT and CAS. Lifetime average traffic-related NOx exposures were assigned using the CALINE4 (California Line Source) dispersion model. Distance to nearest roadways by class was assigned based on ESRI Streetmap Premium roadway data. Results: For each interquartile range increase in average lifetime NOx exposure, we observed a 12.12μm (95% CI: 1.11-23.13; p=0.03) increase in early adulthood attained CIMT and greater longitudinal changes in CIMT from childhood to adulthood (11.5μm, 95% CI: 1.29-21.73, p=0.03) over the follow-up period. Similar adverse changes in CIMT were observed with distance to nearest freeway. Changes in CAS were related to distance to freeway, such that living in closer proximity to freeways was related to greater adverse change in CAS over the follow-up period (stiffness index beta: 0.85; 95% CI: 1.50, 0.21, p=0.01; distensibility: -5.61; 95% CI: -0.93, -10.27, p=0.02).Conclusions: We observed greater adverse changes measures of carotid artery wall thickness and stiffness over time in relation to lifetime traffic-related NOx exposure and residential proximity to freeways. To our knowledge, this is the first study to evaluate the longitudinal impact of lifetime traffic-related air pollution exposure on changes in subclinical markers of atherosclerosis during the critical transition from childhood to adulthood.

Abstract P243: Impact of Menopausal Hormone Therapy on Association Between Heart Fat and Carotid Artery Atherosclerosis Progression in Recently Postmenopausal Women: the KEEPS Trial

Objective: Heart fat depots, within [epicardial adipose tissue (EAT)] and outside [paracardial adipose tissue (PAT)] the pericardium, have been linked to carotid atherosclerosis in various populations. Postmenopausal women have greater volumes of heart fat than premenopausal women. Our previous work suggests that lower endogenous estrogen may contribute to heart fat accumulation, although possibly limited to PAT, while postmenopausal oral hormone therapy (HT) may slow its progression. We evaluated the effect modification of HT use over 48 months on associations between heart fat accumulation and carotid artery intima-media thickness (CIMT) progression in recently postmenopausal women. Methods: The Kronos Early Estrogen Prevention Study (KEEPS) was a multi-center, randomized, double-blind placebo-controlled trial to investigate effects over 48 months of oral conjugated equine estrogens (o-CEE) and transdermal 17β-estradiol (t-E2), both given with cyclic progesterone, compared to placebo, on progression of CIMT in recently postmenopausal women. EAT and PAT volumes, and CIMT were measured at baseline and at 48 months. Associations between the absolute changes in heart fat volumes and CIMT as well as effect modification by HT type were tested using linear regression, adjusting for age, race, study site, employment status, diastolic and systolic blood pressure, anti-hypertensive medications, insulin resistance index, lipids, body-mass index, smoking, alcohol consumption, C-reactive protein, and adipokines. Results: Of 727 randomly assigned women, 467 [mean age (SD): 52.7(2.5); 78.2% Caucasian] had heart fat volumes and CIMT measured at both time points. Overall, changes in EAT and PAT were not associated with CIMT progression; however, assigned treatment significantly modified the association between changes in PAT, but not EAT, and CIMT progression in unadjusted model, P=0.04. In o-CEE group, CIMT progression was 0.028mm (SE:0.01mm) lower, per 1 unit increase in log PAT, than in t-E2 group, P=0.01, and trended 0.017mm (SE:0.01mm) lower than in placebo group, P=0.09. Although adjusted analysis attenuated these findings (P-value for interaction 0.09), differences between o-CEE and t-E2 groups remained significant, P=0.03. Conclusion: HT use modified the association between PAT accumulation, but not EAT, and CIMT progression. Our results suggest a potential beneficial impact of o-CEE (but not transdermal E2) on the relationship between adverse changes in PAT and CIMT. The current findings support the notion that EAT and PAT are distinct fat depots and suggest a complex role of HT in the association between heart fat and CIMT progression in recently postmenopausal women.

PROGRESSION OF CAROTID ARTERY ATHEROSCLEROSIS DURING TREATMENT TO TARGET IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk. The results of works on the impact of antirheumatic therapy on carotid artery (CA) intima-media thickness (IMT) are contradictory. Objective: to assess the time course of changes in CA IMT and CA atherosclerosis (CAA) in patients with early RA during treatment to target at a 18-month follow-up. Subjects and methods. The investigation enrolled patients with early RA (disease duration of less than 12 months), who had not previously taken disease-modifying antirheumatic drugs and glucocorticoids. Duplex scanning (DS) of the CA was performed with IMT measurement at baseline and at 18 months after treatment. Vascular atherosclerotic lesion was recorded when atherosclerotic plaque (ASP) was detected. Starting methotrexate (MTX) monotherapy was prescribed to all the patients, when it showed an insufficient effect at 3 months, a biological agent (BA), such as a tumor necrosis factor-α inhibitor or abatacept, was added. RA remission was noted in 31 (42%) patients at 18 months of treatment. Results and discussion. The investigation included 74 patients with early RA; whose median (Me) age was 56 years, all the patients had moderate or high disease activity (Me DAS28-ESR, 5.4). At baseline, there was increased CA IMT in 51.4% of cases and CAA in 55.4%. At 18 months of treatment, there were no significant IMT changes. New CA ASPs were recorded in 8 (24.2%) patients who had no CAA at the time of inclusion in the investigation (p < 0.05). Nineteen (46.3%) patients were recorded to have the progression that had been identified when including CAA as a considerable increase in the number of ASPs (p < 0.05). The risk of CAA progression was correlated inversely with the mean 18-month level of high-density lipoprotein cholesterol (HDL-Cmean) and directly with the mean concentration of C-reactive protein (CRPmean). There was no significant correlation between HDL-Cmean and CRPmean. The changes of CAA were unassociated with the value of DAS28-ESR, the achievement of RA remission, and antirheumatic therapy (MTX monotherapy, MTX + BA). Conclusion. CAA shows progress in patients with early RA despite they are treated to target. DAS28-ESR remission in RA and ongoing RA treatment option had no substantial impact on the course of CAA. HDL-Cmean and CRPmean are independent risk factors for progression of CAA.

Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy

Background: Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to changes in carotid artery intima-media thickness (CIMT).Methods: Longitudinal study of HIV-infected subjects ≥40 years and on stable antiretroviral therapy (ART) ≥3 months. Peripheral blood mononuclear cells were immunophenotyped by multiparameteric flow cytometry to quantify classical (CD14++CD16–), intermediate (CD14++CD16+), non-classical (CD14low/+CD16++) and transitional (CD14+CD16–) monocyte subsets and activated (CD38+HLA-DR+) CD8+ T-cells at baseline. Plasma biomarkers were assessed by multiplex Luminex assay. High-resolution B-mode ultrasounds of right carotid arteries were obtained. Changes in CIMT over two years at the right common carotid artery (CIMTCCA) and right bifurcation (CIMTBIF) were outcome variables.Results: We studied 50 subjects: 84% male, median age 49 (Q1, Q3; 46, 56) years, median CD4 count 461 (317, 578) cells/mm3, and with HIV RNA ≤ 50 copies/mL in 84%. Change in CIMTBIF correlated with log values of baseline absolute count of non-classical monocytes (r = 0.37, p = 0.020), and with MCP-1 (r = 0.42, p = 0.0024) and TNF-α (r = 0.30, p = 0.036) levels. In multivariable linear regression, only non-classical monocytes and MCP-1 predicted the change in CIMTBIF, independent of Framingham Risk Score and baseline CIMTBIF. No correlation was noted between CD8 T-cell activation and CIMTBIF change. Monocyte subsets, CD8 T-cell activation, and biomarker concentrations were not correlated with changes in CIMTCCA.Conclusions: Our findings highlight the role of non-classical monocytes and MCP-1 in the progression of CIMTBIF in HIV-infected individuals on stable ART independent of traditional cardio-metabolic risk factors.

Effects of lutein and lycopene on carotid intima–media thickness in Chinese subjects with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial

The aim of the present study was to evaluate the effects of lutein and lycopene supplementation on carotid artery intima-media thickness (CAIMT) in subjects with subclinical atherosclerosis. A total of 144 subjects aged 45-68 years were recruited from local communities. All the subjects were randomly assigned to receive 20 mg lutein/d (n 48), 20 mg lutein/d+20 mg lycopene/d (n 48) or placebo (n 48) for 12 months. CAIMT was measured using Doppler ultrasonography at baseline and after 12 months, and serum lutein and lycopene concentrations were determined using HPLC. Serum lutein concentrations increased significantly from 0·34 to 1·96 μmol/l in the lutein group (P< 0·001) and from 0·35 to 1·66 μmol/l in the combination group (P< 0·001). Similarly, serum lycopene concentrations increased significantly from 0·18 to 0·71 μmol/l in the combination group at month 12 (P< 0·001), whereas no significant change was observed in the placebo group. The mean values of CAIMT decreased significantly by 0·035 mm (P= 0·042) and 0·073 mm (P< 0·001) in the lutein and combination groups at month 12, respectively. The change in CAIMT was inversely associated with the increase in serum lutein concentrations (P< 0·05) in both the active treatment groups and with that in serum lycopene concentrations (β = - 0·342, P= 0·031) in the combination group. Lutein and lycopene supplementation significantly increased the serum concentrations of lutein and lycopene with a decrease in CAIMT being associated with both concentrations. In addition, the combination of lutein and lycopene supplementation was more effective than lutein alone for protection against the development of CAIMT in Chinese subjects with subclinical atherosclerosis, and further studies are needed to confirm whether synergistic effects of lutein and lycopene exist.

Biomarkers of Microbial Translocation and Macrophage Activation: Association With Progression of Subclinical Atherosclerosis in HIV-1 Infection

The relationships between soluble CD14 (sCD14), endotoxin (lipopolysaccharide [LPS]), and progression of atherosclerosis have not been defined in human immunodeficiency virus (HIV) infection. We retrospectively assessed serum sCD14 and LPS levels of 91 subjects in a prospective 3-year study of carotid artery intima-media thickness (CIMT) (AIDS Clinical Trials Group [ACTG] 5078), where subjects were enrolled as risk factor-controlled triads of HIV-uninfected (n = 36) and HIV-infected individuals with (n = 29) or without (n = 26) protease inhibitor (PI)-based therapy for ≥2 years. The primary end point was the yearly rate of change of CIMT (ΔCIMT). In multivariate analysis of the HIV-infected subjects, each 1 µg/mL above the mean of baseline serum sCD14 corresponded to an additional 1.52 µm/y (95% confidence interval, .07-2.98; P = .04) in the ΔCIMT. Every 100 pg/mL above the mean of baseline serum LPS corresponded to an additional 0.49 µm/y (95% confidence interval, .18-.81; P = .003) in the ΔCIMT. However, in univariate analysis in the HIV-uninfected group sCD14 (P = .33) and LPS (P = .27) levels were not associated with higher ΔCIMT. HIV infection and PI therapy were not associated with baseline serum LPS and sCD14 levels (P > .1). Our data are among the first to suggest that serum biomarkers of microbial translocation (LPS) and macrophage activation (sCD14) predict subclinical atherosclerosis progression in HIV-infected persons.

Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia

Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown.We conducted a double-blind, randomized, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia. Patients underwent B-mode ultrasonography to assess the intima-media thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intima-media thickness, which was defined as the average of the means of the far-wall intima-media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries.The primary outcome, the mean (+/-SE) change in the carotid-artery intima-media thickness, was 0.0058+/-0.0037 mm in the simvastatin-only group and 0.0111+/-0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intima-media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean (+/-SD) LDL cholesterol level was 192.7+/-60.3 mg per deciliter (4.98+/-1.56 mmol per liter) in the simvastatin group and 141.3+/-52.6 mg per deciliter (3.65+/-1.36 mmol per liter) in the combined-therapy group (a between-group difference of 16.5%, P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups.In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima-media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097 [ClinicalTrials.gov].).

Brachial artery vasoreactivity is associated with cross-sectional and longitudinal anatomical measures of atherosclerosis in postmenopausal women with coronary artery disease

Background The diagnostic and prognostic importance of brachial artery flow-mediated dilation (BFMD) for cardiovascular disease (CVD) is not certain and associations between BFMD and recognized measures of atherosclerosis have not been well established. Methods We investigated cross-sectional and longitudinal correlations between repeated measures of BFMD and quantitative coronary artery angiographic (QCA) measurements of average percent diameter stenosis, number of lesions and minimum luminal diameter (MLD), and ultrasonographic measurement of carotid artery intima-media thickness (CIMT) in an ethnically diverse cohort of postmenopausal women ( n = 132) with coronary artery disease (CAD). Subjects were participants in a 3-year randomized, placebo-controlled clinical trial, testing the efficacy of hormone therapy on atherosclerosis progression. Associations between BFMD and QCA measures, and between BFMD and CIMT were examined using measurements from the same study visit. Results BFMD was significantly inversely correlated with coronary artery stenosis at baseline ( β = −1.21% [S.E.( β) = 0.38], p = 0.002). BFMD levels significantly predicted rate of change in CIMT over the trial period ( β = −0.76 μm/year [S.E.( β) = 0.29], p = 0.008). Conclusions Physiological and anatomical measures of atherosclerosis are correlated among postmenopausal women with CAD, which provides some validation of BFMD as a measure of atherosclerosis in high-risk populations.

A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes

Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. We investigated the effects of these medications on high-sensitivity C-reactive protein (hsCRP) and carotid artery intima-media thickness (CIMT) to determine their relative potential to reduce cardiovascular risk independent of their antihyperglycemic actions. Ninety-two subjects with suboptimally controlled diabetes mellitus (hemoglobin A1c [HbA1c] >7.0%) were assigned to therapy with either rosiglitazone 4 mg once daily or metformin 850 mg twice daily for 24 weeks. The primary end point was the change in hsCRP after 24 weeks. The change in CIMT was prespecified as a secondary end point. Metformin and rosiglitazone treatment led to similar significant improvements in glycemic control (HbA1c -1.08% in the rosiglitazone group and -1.18% in the metformin group, P = nonsignificant). High-sensitivity C-reactive protein levels decreased by an average of 68% in the rosiglitazone group (5.99 +/- 0.88 to 1.91 +/- 0.28 mg/L, P < .001), compared with a nonsignificant 4% reduction in hsCRP with metformin (5.69 +/- 0.83 to 5.46 +/- 0.92 mg/L; P = nonsignificant). Maximal CIMT progressed in the metformin group (+0.084 +/- 0.038 mm), whereas regression of maximal CIMT was observed in the rosiglitazone group (-0.037 +/- 0.031 mm; P = .02 for the between group comparison). Similar changes were observed for mean CIMT. The change in hsCRP and maximal CIMT were related in a multivariable model controlling for changes in HbA1c and lipid parameters (r = .31; P = .01). Rosiglitazone, compared to metformin, induced a prompt and profound reduction in hsCRP levels independent of its effect on glycemia. This change was associated with regression of CIMT after 24 weeks.

Effect of Antihypertensive Therapy on Progression of Carotid Intima-Media Thickness in Patients With Type 2 Diabetes Mellitus

Antihypertensive therapy reduces the incidence of cardiovascular events in people with diabetes mellitus (DM). However, the effects of treatment on subclinical atherosclerosis are less well studied. Results of a post hoc cohort analysis of the association between antihypertensive treatment and carotid artery intima-media thickness (CIMT) in the Troglitazone Atherosclerosis Regression Trial (TART), a randomized trial designed to evaluate the impact of troglitazone treatment on CIMT progression in adults with insulin-requiring type 2 DM, are reported. CIMT, blood pressure (BP), and use of antihypertensive agents were measured throughout the 2-year treatment period. In multivariable mixed-effects models, the annual rate of change in CIMT in relation to BP and duration of antihypertensive agent use, adjusting for covariates, was evaluated. Higher systolic BP was associated with a higher CIMT progression rate (p=0.03). This association was reduced by antihypertensive treatment in a duration-dependent manner (p for interaction=0.035). Adjustment for age, treatment assignment, and change in fasting glucose during the trial did not attenuate these associations. In conclusion, regular use of antihypertensive agents reduces the harmful impact of increased BP on atherosclerosis progression in patients with DM. The antiatherogenic effect of antihypertensive agents, including BP normalization and possible direct vascular wall protection, can be detected by CIMT progression using B-mode ultrasound in patients with DM.

Carotid artery intima-media thickness and lipid profile in adults with growth hormone deficiency after long-term growth hormone replacement

To investigate the effects of growth hormone (GH) replacement on carotid artery intima-media thickness (IMT) and lipid profile, 29 adults with GH deficiency (GHD), mean age 42.5 ± 10.1 years, were studied and compared with 29 control subjects matched for sex, age, body mass index, and smoking habits. Lipid profile (total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoproteins A and B, and lipoprotein), serum insulin-like growth factor 1 (IGF-1) levels, and ultrasonography of the carotid arteries were performed at baseline and at 6, 12, and 24 months during GH therapy on maintenance dose. At baseline, when compared with the control group, patients presented increased carotid artery IMT ( P < .05) and triglyceride levels ( P < .001) and lower HDL concentrations ( P < .01). In a linear regression analysis, age and known mean duration of GHD were correlated with carotid artery IMT. After 24 months of GH replacement, a reduction in the mean of carotid artery IMT was observed ( P < .01). The apolipoprotein B levels decreased significantly after the first 3 months of GH treatment ( P < .001) and remained stable thereafter. Women also presented an increase in HDL cholesterol levels ( P < .01). No differences were observed in the other lipids measured. Carotid artery IMT at baseline was inversely correlated with the change in carotid artery IMT (Δ = 24 months − baseline), r = 0.63, P < .001. In conclusion, 24 months of GH replacement therapy promoted favorable effects on carotid artery IMT and lipid profile in patients with GHD. Long-term follow-up studies are required to show whether these beneficial effects will result in reduction of morbidity and mortality from vascular disease.

Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men.

To investigate the association between plasma oxidized low-density lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as measured by ultrasound in the carotid arteries. Prospective, observational study with more than 3 years of follow-up. One-centre study at university hospital. The subjects (n = 326) were obtained by stratified sampling from a population sample of men who were 58 years old at baseline. Carotid artery intima-media thickness (IMT) was measured bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up. Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk factors were measured at study entry. Automated measurements of IMT were performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL at entry was measured by a specific monoclonal antibody, mAb-4E6. OxLDL at entry, but not LDL cholesterol, was associated with the number and size of plaques at follow-up (P = 0.008), also after adjustment for plaque status at entry (P = 0.033). The plasma OxLDL concentration at entry was associated with change in carotid artery IMT (r = 0.17; P = 0.002) and in a stepwise multiple regression analysis this association remained after adjustment for other cardiovascular risk factors (P = 0.005). These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors.

Apolipoprotein B/apolipoprotein A-I in relation to the metabolic syndrome and change in carotid artery intima-media thickness during 3 years in middle-aged men.

The apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio is a measure of the relationship between different lipoprotein particles and a powerful predictor of coronary death. The aim was to examine whether apoB/apoA-I was associated with the metabolic syndrome (MetS) at baseline and also with the future change in carotid artery intima-media thickness (IMT). In 313 58-year-old men, carotid artery IMT was measured bilaterally by high-resolution B-mode ultrasound at baseline and after 3 years of follow-up. Serum apolipoprotein concentrations and the components of MetS were measured at study entry. ApoB/apoA-I showed statistically significant associations with body mass index, waist-to-hip ratio, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein (LDL) particle size, insulin, and diastolic blood pressure. Two thirds of the patients with MetS had high apoB/apoA-I ratios (>0.90) compared with one third of those without the syndrome (P<0.001). The IMT change was associated with apoB, total cholesterol, LDL cholesterol, triglycerides, and inversely with HDL cholesterol and LDL particle size at entry, and there was a strong colinearity between these variables. The subjects with apoB/apoA-I above the first tertile (0.74) had a 20-microm-higher (95% CI, 7 to 33) annual increase in IMT compared with those below this level after adjustment for blood pressure and smoking. The apoB/apoA-I ratio was strongly associated with MetS and its components at baseline. ApoB/apoA-I at baseline was related to the change in carotid artery IMT during 3 years of follow-up. There was a strong colinearity between apoB/apoA and the atherogenic lipids.