Carotid Intima-media Wall Thickness Research Articles

Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity

Previous studies investigating cardiovascular (CV) risk in obese women with polycystic ovary syndrome (PCOS) have been potentially confounded by not adequately accounting for body weight. To assess if PCOS increases CV risk independently in young obese women by examining carotid intima-media wall thickness (cIMT) and platelet function. A case-control study comparing women with PCOS (n = 21) to age (32·8 ± 7·2 vs 33·5 ± 6·7 years), and weight (100·9 ± 16·7 vs 99·3 ± 14·7 kg)-matched controls (n = 19). Platelet function was examined by flow cytometry, clot structure and fibrinolysis by turbidimetric assays and endothelial function by ELISA and post ischaemic reactive hyperaemia. The PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nmol/l (P = 0·01), HOMA-IR 2·5 ± 1·7 vs 1·7 ± 1·0 (P = 0·08), impaired glucose regulation 33·3% vs 5·3% (P = 0·02), and urinary isoprostane 16·0 ± 4·4 vs 11·8 ± 7·1 ng/ml (P = 0·04) compared to controls. Mean cIMT 0·5 ± 0·05 vs 0·48 ± 0·06 mm (P = 0·36), and basal platelet surface expression (percentage of positive cells) of P-selectin 0·52 ± 0·3 vs 0·43 ± 0·23 (P = 0·40) and fibrinogen binding 0·97 ± 0·4 vs 0·83 ± 0·3 (P = 0·48) did not significantly differ between the PCOS and control groups respectively. Furthermore, platelets sensitivity to stimulation with adenosine-5'-diphosphate or inhibition with prostacyclin, clot structure and fibrinolytic efficiency ex vivo, endothelial reactive hyperaemic index (RHI), inflammation (hsCRP) and adhesion markers (sE-selectin, sP-selectin, sVCAM-1 and sICAM-1) were not significantly different between the two groups. PCOS appeared not to independently increase atherothrombotic risk when matched for obesity. It is likely that any excess CV risk in young obese women with PCOS can either be attributed to obesity or is not yet apparent at this early stage of the condition.

Comparison of Factors Associated with Carotid Intima-Media Thickness in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR)

The measurement of carotid intima-media thickness (CIMT) is a valid method to quantify levels of atherosclerosis. The present study was conducted to compare the strengths of associations between CIMT and cardiovascular risk factors in two different populations. The Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (HNR) are two population-based prospective cohort studies of subclinical cardiovascular disease. All Caucasian subjects aged 45 to 75 years from these cohorts who were free of baseline cardiovascular disease (n = 2,820 in HNR, n = 2,270 in MESA) were combined. CIMT images were obtained using B-mode sonography at the right and left common carotid artery and measured 1 cm starting from the bulb. In both studies, age, male sex, and systolic blood pressure showed the strongest association (P < .0001 for each) for a higher CIMT. The mean of mean far wall CIMT was slightly higher in MESA participants (0.71 vs 0.67 mm). Almost all significant variables were consistent between the two cohorts in both magnitude of association with CIMT and statistical significance, including age, sex, smoking, diabetes, cholesterol levels, and blood pressure. For example, the association with systolic blood pressure was (ΔSD = 0.011; 95% confidence interval, 0.0009 to 0.014) per mm Hg in MESA and (ΔSD = 0.010; 95% confidence interval, 0.005 to 0.021) per mm Hg in HNR. This consistency persisted throughout the traditional (Framingham) risk factors. A comparison of the associations between traditional cardiovascular risk factors and CIMT across two culturally diverse populations showed remarkable consistency.

Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity

SummaryIntroduction Previous studies investigating cardiovascular (CV) risk in obese women with polycystic ovary syndrome (PCOS) have been potentially confounded by not adequately accounting for body weight. Objective To assess if PCOS increases CV risk independently in young obese women by examining carotid intima-media wall thickness (cIMT) and platelet function. Design A case–control study comparing women with PCOS (n = 21) to age (32·8 ± 7·2 vs 33·5 ± 6·7 years), and weight (100·9 ± 16·7 vs 99·3 ± 14·7 kg)-matched controls (n = 19). Platelet function was examined by flow cytometry, clot structure and fibrinolysis by turbidimetric assays and endothelial function by ELISA and post ischaemic reactive hyperaemia. Results The PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nmol/l (P = 0·01), HOMA-IR 2·5 ± 1·7 vs 1·7 ± 1·0 (P = 0·08), impaired glucose regulation 33·3% vs 5·3% (P = 0·02), and urinary isoprostane 16·0 ± 4·4 vs 11·8 ± 7·1 ng/ml (P = 0·04) compared to controls. Mean cIMT 0·5 ± 0·05 vs 0·48 ± 0·06 mm (P = 0·36), and basal platelet surface expression (percentage of positive cells) of P-selectin 0·52 ± 0·3 vs 0·43 ± 0·23 (P = 0·40) and fibrinogen binding 0·97 ± 0·4 vs 0·83 ± 0·3 (P = 0·48) did not significantly differ between the PCOS and control groups respectively. Furthermore, platelets sensitivity to stimulation with adenosine-5′-diphosphate or inhibition with prostacyclin, clot structure and fibrinolytic efficiency ex vivo, endothelial reactive hyperaemic index (RHI), inflammation (hsCRP) and adhesion markers (sE-selectin, sP-selectin, sVCAM-1 and sICAM-1) were not significantly different between the two groups. Conclusions PCOS appeared not to independently increase atherothrombotic risk when matched for obesity. It is likely that any excess CV risk in young obese women with PCOS can either be attributed to obesity or is not yet apparent at this early stage of the condition.

The ABCG8 G574R Variant, Serum Plant Sterol Levels, and Cardiovascular Disease Risk in the Old Order Amish

To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis. In Old Order Amish participants aged 18 to 85 years, with (n=110) and without (n=181) 1 copy of the ABCG8 G574R variant, we compared mean plasma levels of plant sterols and cholesterol precursors and carotid intima-media wall thickness. Carriers of a single 574R allele had increased plant sterol levels (eg, 35%-37% higher plasma levels of sitosterol, campesterol, and stigmasterol) and increased plant sterol/cholesterol ratios (P<0.001 for all). 574R carriers had significantly decreased levels of lathosterol and lanosterol, precursors in a pathway for endogenous cholesterol synthesis, suggesting that plant sterols may alter regulation of genes involved in cholesterol synthesis. The G574R variant was not associated with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels. Compared with noncarriers, 574R carriers had decreased carotid intima-media wall thickness (0.62 versus 0.66 mm; age- and sex-adjusted P=0.03). Adjustment for body weight, blood pressure, and standard lipid measures (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) did not alter this association. Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.

Abstract 9771: Aggressive Treatment of Cardiovascular Risk Factors: Effects on Atherosclerosis and Arterial Age

Background: Atherosclerosis, the major cause of cardiovascular disease (CVD), involves the abnormal deposit of cholesterol within the intima of the arterial wall. Arteriosclerosis is the annual thickening (roughly 0.01 mm per year) of the arterial wall (media) based generally on aging. An indirect method of diagnosing atherosclerosis involves ultrasound analysis of the common carotid intima-media wall thickness (CCIMT) to evaluate a patient's arterial age. Arterial age is a term representing the combination of wall thickness based both on atherosclerosis and arteriosclerosis. Hypothesis: Aggressively treating CVD risk factors will reduce atherosclerosis and arterial age as measured by CCIMT analysis. Methods: An observational study of 220 patients (121 m, mean age 58 yrs) treated in a CVD prevention clinic and with at least 1 CVD risk factor. Two ultrasounds were performed by the same sonographer, approximately 3 years apart, with a computerized edge-detection device (MICROMAXX, Sonosite) measuring 100 markers within 1 cm area of the CCIMT wall, 1 cm proximal to the bulb, to provide the maximum thickness. Arterial age was estimated based on data of previous epidemiology studies stored within the MICROMAXX. Results: After a mean follow up of 3.05 years, the observed values for maximum CCIMT (see table) were significantly lower (p&lt;0.0001) than expected. While patients' chronological age increased by 3 years, their arterial age decreased by 1.53 years (p&lt;0.0001), translating into a 4.57 year difference compared to the expected change. Reduction of total cholesterol was the only risk factor found to be significantly associated with reduction in vascular age (p&lt;.027). Conclusion: In patients with CVD risk factors, aggressive clinical treatment resulted in statistically significant reductions in the rate of maximum CCIMT progression and reversing arterial age. Longer follow-up is needed to determine if these findings also translate to fewer clinical events.

Chronic Obstructive Pulmonary Disease and Lipid Core Carotid Artery Plaques in the Elderly

Chronic obstructive pulmonary disease (COPD) is an independent risk factor for ischemic stroke and the risk increases with severity of airflow limitation. Even though vulnerable carotid artery plaque components, such as intraplaque hemorrhage and lipid core, place persons at high risk for ischemic events, the plaque composition in patients with COPD has never been explored. To investigate the prevalence of carotid wall thickening, the different carotid artery plaque components, and their relationship with severity of airflow limitation in elderly patients with COPD. This cross-sectional analysis was part of the Rotterdam Study, a prospective population-based cohort study performed in subjects aged 55 years and older. Diagnosis of COPD was confirmed by spirometry. Participants with carotid wall intima-media thickness greater than or equal to 2.5 mm on ultrasonography underwent high-resolution magnetic resonance imaging for characterization of carotid plaques. Data were analyzed using logistic regression. COPD cases (n = 253) had a twofold increased risk (odds ratio, 2.0; 95% confidence interval, 1.44-2.85; P < 0.0001) of presentation with carotid wall thickening on ultrasonography compared with control subjects with a normal lung function (n = 920). Moreover, the risk increased significantly with severity of airflow limitation. On magnetic resonance imaging, vulnerable lipid core plaques were more frequent in COPD cases than in control subjects (odds ratio, 2.1; 95% confidence interval, 1.25-3.69; P = 0.0058). Carotid artery wall thickening is more prevalent in patients with COPD than in control subjects. In elderly subjects with carotid wall thickening, COPD is an independent predictor for the presence of a lipid core, and therefore of vulnerable plaques.

Relationship between inflammatory markers, oxidant–antioxidant status and intima-media thickness in prepubertal children with juvenile idiopathic arthritis

To investigate the presence of possible early atherosclerotic changes in a group of prepubertal children with juvenile idiopathic arthritis (JIA) and to establish the potential beneficial effects of 1-year treatment. Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate), proinflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α), lipid profile and oxidant-antioxidant status (urinary isoprostanes [PGF-2α]) were assessed in 38 JIA children (12M/26F, mean age 7.05±2.39years) and compared with 40 controls (18M/22F, mean age 6.34±2.25years). Carotid intima-media wall thickness (cIMT) was obtained and blood pressure was measured. All parameters were reassessed in JIA children after 1year of therapy. At baseline JIA children presented compared to controls higher levels of inflammatory markers, proinflammatory cytokines, total cholesterol, LDL cholesterol, and PGF-2α (all p≤0.01). Furthermore, blood pressure and cIMT were significantly increased (both p≤0.01). After a 1-year treatment with non-steroid anti-inflammatory (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs), a significant reduction of all parameters was detected (all p≤0.01). This was associated with a significant reduction in blood pressure and cIMT (both p≤0.01). Within the JIA group, patients requiring etanercept presented worse laboratory values and cIMT measurements at baseline. Nevertheless, the same improvement of all parameters was obtained after a 1-year treatment. In stepwise multiple regression, LDL cholesterol and IL-1β were mainly related to cIMT. Chronic and systemic inflammation seems to lead to early atherosclerotic abnormalities even in pre-pubertal JIA children. Substantial improvement can be obtained with 1-year of appropriate therapy.

Carotid artery intima-media thickness and brachial artery flow-mediated vasodilatation in patients with rheumatoid arthritis

Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA). Our study aim was to determine the relationship between carotid artery intima-media wall thickness (IMT) and flow-mediated endothelium-dependent vasodilatation (FMD) in a patients with RA, in context with clinical and laboratory measurements. Fifty-two patients with RA and 30 matched healthy controls without clinically evident CV disease were studied. Brachial and carotid ultrasonography was performed to determine FMD and IMT, respectively. We also assayed immunological, inflammatory and metabolic laboratory markers. IMT was significantly higher in RA patients (1.00 ± 0.16 mm) patients than in controls (0.89 ± 0.13 mm) (P = 0.001). FMD was significantly lower in RA (9.16 ± 7.03) as compared to controls (12.60 ± 5.49) (p = 0.005). RA patients had significant positive correlations between erythrocyte sedimentation rate (ESR) (r=0.395 p = 0.021) and IMT and negative correlation between visual analog scale (VAS) (r= -0.311, p= 0.025) and IMT. RA patients who used low doses of corticosteroids have, statistically, significantly better FMD, than those who do not use corticosteroids. Linear regression analysis revealed that IMT was related to tender joint count (p = 0.008), VAS (p < 0.001), ESR (p = 0.048) and total cholesterol/high density lipoprotein cholesterol ratio (p = 0.039). In patients with RA, FMD was impaired and IMT was increased, indicating early endothelial dysfunction and accelerated atherosclerosis. Early treatment of disease may reduce the risk of atherosclerosis in RA.

The prevalence and characteristics of metabolic syndrome in urban Malaysian HIV-infected patients

Background: Cardiovascular disease (CVD) has become more prevalent among the HIV-infected patients. Whether or not highly active antiretroviral treatment (HAART) alone directly contributes to subclinical atherosclerosis in HIV-infected patients is controversial. We aim to determine the association between HAART and subclinical atherosclerosis. Methods: All patients attending the HIV clinic in University of Malaya Medical Centre from July 2011 until January 2012 were included. Patients with symptomatic HIV, established coronary heart disease, hypertension, dyslipidaemia and diabetes mellitus were excluded from the study. Patients were examined for blood pressure and anthropometric measurements. History of tobacco consumption and family history of coronary artery disease were obtained. Biochemical analysis comprises oral glucose tolerance test, full lipid profiles (after a 10-hour fasting), CD4 cell counts and HIV RNA viral load. Analysis of carotid intima-media wall thickness (CIMT) was carried out by a single trained ultrasonographer throughout the study period using the high-resolution B-mode ultrasonography. Subclinical atherosclerosis was defined as the presence of plaque (focal echogenic structure with CIMT.1.2mm), or CIMT>0.8mm. Results: 109 HIV-infected patients were enrolled in this study. 93 (85.3%) were on HAART and 16 (14.7%) were HAART-naive. A total of 45 (41.3%) patients had subclinical atherosclerosis and out of that 41 (91%) were on HAART. Subclinical atherosclerosis was significantly associated with age, waist circumference, total cholesterol, duration of HIV infection and duration of exposure to HAART, (p <0.05). Other significant factors associatedwith subclinical atherosclerosis were hypertension (OR=2.4; 95% CI 1.1-5.4), high triglyceride (OR=2.9; 95% CI 1.3-6.7) and exposure to Zidovudine (OR=2.5; 95% CI 1.1-6.0). However, there were no significant association between family history of CVD, smoking and diabetes to subclinical atherosclerosis. Conclusion: Both duration of HIV-infection and exposure to HAART were associated with subclinical atherosclerosis in HIV-infected patients. When individual HAART were analyzed, Zidovudine has significant association to subclinical atherosclerosis.

Association Study of MIA3 rs17465637 Polymorphism with Cardiovascular Disease in Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis. Melanoma inhibitor protein 3 (MIA3) is required for the export of collagen VlI (COL7A1) from the endoplasmic reticulum and it appears to be a tumor suppressor of malignant melanoma. Genome-wide association studies have described an association between MIA3 rs17465637 A/C polymorphisms and coronary artery disease and myocardial infarction. Because of that, we assessed the MIA3 rs17465637 polymorphism in 1505 RA Spanish patients stratified according to the presence/absence of cardiovascular (CV) disease. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using carotid ultrasound to establish carotid intima-media wall thickness and carotid plaques and brachial ultrasonography to determine the presence of endothelial dysfunction by flow-mediated endothelium-dependent and independent vasodilatation. MIA3 rs17465637 allele A showed a trend for association with the presence of carotid plaques (odds ratio 1.56, 95% confidence interval [0.96-2.51]; p=0.07). However, apart from an association of the MIA3 rs17465637 A allele with the risk of CV events in RA patients with dyslipidemia (p=0.018), no other significant associations were found between the presence of MIA3 rs17465637 A allele and the risk of suffering CV events or other surrogate markers of atherosclerosis. In conclusion, our results suggest a potential association of the MIA3 rs17465637 with CV disease in dyslipidemic patients with RA. However, additional studies are required to better establish the role of the MIA3 gene in mechanisms leading to the accelerated atherogenesis observed in RA.

Lack of association between the CXCL12 rs501120 polymorphism and cardiovascular disease in Spanish patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis. CXCL12 is a strong chemotactic signal for lymphocytes. Because previous genome-wide association studies demonstrated an association between CXCL12 rs501120 and coronary artery disease, in the present study we assessed the potential association of this polymorphism with the risk of cardiovascular (CV) disease in 1,321 Spanish patients with RA. A subgroup of patients without CV events was also studied to determine the presence of subclinical atherosclerosis by ultrasonography (brachial flow-mediated endothelium-dependent vasodilatation and carotid intima-media wall thickness). However, no significant differences in genotypic and allelic frequencies between RA patients with and without CV events were observed, as was also the case when values of surrogate markers of atherosclerosis were assessed according to CXCL12 rs501120 genotype frequencies. In conclusion, our results do not confirm an association of the CXCL12 rs501120 polymorphism with atherosclerosis or with CV disease in RA.

Anti-TNF-Alpha-Adalimumab Therapy Is Associated with Persistent Improvement of Endothelial Function without Progression of Carotid Intima-Media Wall Thickness in Patients with Rheumatoid Arthritis Refractory to Conventional Therapy

To determine whether treatment with the anti-TNF-alpha blocker adalimumab yields persistent improvement of endothelial function and prevents from morphological progression of subclinical atherosclerosis in patients with rheumatoid arthritis (RA) refractory to conventional therapy, a series of 34 consecutive RA patients, attending hospital outpatient clinics and who were switched from disease modifying antirheumatic drug therapy to anti-TNF-alpha-adalimumab treatment because of severe disease, were assessed by ultrasonography techniques before the onset of adalimumab therapy (at day 0) and then at day 14 and at month 12. Values of flow-mediated endothelium-dependent vasodilatation at day 14 and at month 12 were significantly higher (mean ± standard deviation (SD): 6.1 ± 3.9%; median: 5.7% at day 14, and mean ± SD: 7.4 ± 2.8%; median: 6.9% at month 12) than those obtained at day 0 (mean: 4.5 ± 4.0%; median: 3.6%; P = 0.03 and P < 0.001, resp.). Endothelium-independent vasodilatation results did not significantly change compared with those obtained at day 0. No significant differences were observed when carotid artery intima-media wall thickness values obtained at month 12 (mean ± SD: 0.69 ± 0.21 mm) were compared with those found at day 0 (0.65 ± 0.16 mm) (P = 0.3). In conclusion, anti-TNF-alpha-adalimumab therapy has beneficial effects on the development of the subclinical atherosclerosis disease in RA.

Atherosclerosis in Rheumatoid Arthritis

There is a growing body of evidence supporting an increased risk of cardiovascular (CV) mortality in patients with rheumatoid arthritis (RA). This is the result of complex mechanisms leading to accelerated atherosclerosis [1]. In this regard, besides classic CV risk factors [2], chronic inflammation [3] and a genetic component [3, 4] have been proposed to influence the development of atherosclerosis in RA. This special issue encompasses different aspects of the CV disease associated to RA. With respect to this, the link between atherosclerosis and RA was discussed. Surrogate markers of atherosclerosis have been found to be useful in predicting the presence of atherosclerosis disease in subclinical stages in adults with RA [5, 6]. Data shown in this special issue also confirmed that children with juvenile idiopathic arthritis may have higher carotid intima-media wall thickness index values than controls. These observations emphasize the need for increased awareness of the risk of atherosclerosis in children with juvenile idiopathic arthritis. An exhaustive literature review on the genetic influence in the development of CV disease in patients with RA was also included. With respect to this, it is important to keep in mind that besides gene polymorphisms located within the MHC region [3, 4], variations of genes located outside this region, such as CCR5, MTHF [7, 8], are of potential relevance in the increased risk of CV disease associated to RA. Adipokines are molecules not only implicated in the development of metabolic syndrome but also in inflammatory mechanisms that may play a role in the pathogenesis of different autoimmune diseases [9, 10]. A timely review on the implication of adipokines in the development of the atherosclerotic disease not only focusing on RA but also discussing the link between these molecules and the presence of atherosclerosis in other chronic inflammatory rheumatic diseases was included in the special issue. The mechanisms associated with endothelial dysfunction, an early step in the atherogenesis process, in patients with RA are far from being completely understood. In this special issue an assessment of the potential role of asymmetric dimethylarginine and apelin as biomarkers to detect early data of endothelial dysfunction in patients with RA was included. Anti-TNF-α drugs constitute the mainstay of therapy in RA patients with severe disease that is refractory to conventional disease modifying antirheumatic drugs. One of the articles included in the special issue confirmed the previously reported short-term beneficial effect of the fully human-anti-TNF-α monoclonal antibody adalimumab on endothelial function [11]. In addition, new data showing persistent improvement of endothelial function in adalimumab-treated RA patients without progression of the carotid intima-media thickness are reported. This is of potential relevance as the use of anti-TNF-α therapy has been associated with a decrease of mortality in RA patients, mainly due to a reduction in the incidence of CV events [12]. In line with the above, Popa et al. had previously assessed the effects of the anti-TNF-α therapy on the HDL antiatherogenic function. They observed that infliximab, a chimeric anti-TNF-α monoclonal IgG1 antibody was able to improve HDL antioxidative capacity. This effect was sustained 6 months after anti-TNF-α therapy had been initiated [13]. In this special issue the same group conducted an extensive review on the effect that different biologic therapies exert on the atherogenic index and HDL cholesterol in patients with RA. Taken together, these studies confirm the presence of complex mechanisms that influence the development of atherosclerosis in RA. Nevertheless, further studies are needed to shed light on the problem of augmented risk of CV disease in patients with RA. Miguel A. Gonzalez-Gay Zoltan Szekanecz Calin D. Popa Patrick Dessein

Indicators of the atherogenic lipoprotein phenotype measured with density gradient ultracentrifugation predict changes in carotid intima-media thickness in men and women

ObjectiveProgression of carotid intima-media thickness (CIMT) is a surrogate indicator for the early stages of atherosclerosis.MethodsThe study investigated relationships between baseline lipoprotein cholesterol, triglyceride (TG), and apolipoprotein (Apo) B levels assessed with density gradient ultracentrifugation (DGU) and progression of posterior wall common CIMT in men (45–75 years of age) and women (55–74 years of age) in the control arm of a clinical trial. Participants had baseline posterior wall CIMT 0.7–2.0 mm, without significant stenosis. CIMT was assessed using B-mode ultrasound at baseline, and 12 and ~18 months. A DGU cholesterol panel that assessed the major lipoprotein classes and subclasses, plus triglycerides, lipoprotein (a) cholesterol, low-density lipoprotein (LDL) peak time (inversely related to LDL particle density), and Apo B were performed on fasting baseline samples. Apo B was also measured using an enzyme linked immunosorbent assay.ResultsBaseline CIMT was inversely associated (P < 0.001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of posterior wall CIMT progression in linear regression analyses included LDL peak time (inverse, P = 0.045), total high-density lipoprotein cholesterol (HDL-C) (inverse, P = 0.001), HDL2-C (inverse, P = 0.005), HDL3-C (inverse, P = 0.003), very low-density lipoprotein (VLDL)-C (P = 0.037), and VLDL1+2-C (P = 0.016).ConclusionThese data indicate that DGU-derived indicators of the “atherogenic lipoprotein phenotype,” including increased TG-rich lipoprotein cholesterol, lower HDL-C and HDL-C subfractions, and a greater proportion of LDL-C carried by more dense LDL particles, are associated with CIMT progression in men and women at moderate risk for coronary heart disease.

Cerebrovascular disorders: carotid-wall intima-media thickness, stroke recurrence, and β-blocker selectivity

It is always amazing to see how many articles are published in the field of cerebrovascular disorders every month, even in very high-ranking journals. This is most certainly justified because daily clinical practice shows how relevant cerebrovascular disorders are. The three articles discussed in this month’s Journal Club primarily focus on primary or secondary prophylaxis. In the first study published in the New England Journal of Medicine, intima-media thickness of the walls of the common carotid artery and internal carotid artery, as well as the presence of plaque, were identified as a predictor for cardiovascular outcomes. The second article deals with stroke recurrence within the time window recommended for carotid endarterectomy, i.e. within 2 weeks after the first stroke due to a carotid stenosis. The article shows that early recurrent stroke risk was indeed high, particularly within the first 72 h, which has a considerable clinical impact. The final article, a systematic review on the effects of b-blocker selectivity on blood pressure variability and stroke also has clinical implications: non-selective b-blockers should be avoided in neurologic practice. In other words, b1-selective blockers can be used with the exception of atenolol, which has been shown not to be effective for stroke prevention. Carotid-wall intima-media thickness and cardiovascular events Known risk factors for cardiovascular events are increased systolic blood pressure, cholesterol, diabetes, cigarettesmoking, age, male sex, and history of cardiovascular disease. On the other hand, patients clearly benefit from hypertension treatment. In the current study, Polak and co-workers from Boston University examined whether intima-media thicknesses of the walls of the common carotid artery and internal carotid artery are independent risk factors and, further, if they may add to the Framingham risk score for predicting cardiovascular events. In 2,965 members of the Framingham Offspring Study cohort, the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery as well as the presence of plaque (defined as intima-media thickness of the internal carotid artery of more than 1.5 mm) were measured. Of these 2,965 participants a total of 296 had a cardiovascular event. The major findings were as follows: First, in the group of patients with no cardiovascular disease at follow-up the mean common carotid artery thickness was 0.59 ± 0.13 versus 0.66 ± 0.15 mm in the group of patients with cardiovascular disease at follow-up. Second, in those with no cardiovascular disease at follow-up the maximum internal carotid artery thickness was 1.30 ± 0.79 versus 1.9 ± 1.00 mm in those with cardiovascular disease at follow-up. Third, 27.4% of patients with no cardiovascular disease at follow-up had evidence of a plaque versus 59.6% of those with cardiovascular disease at follow-up. Fourth, the above-mentioned risk factors predicted the cardiovascular events with a so-called C statistic of 0.748. Fifth, the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal

Aterosclerosis en sujetos con periodontitis

Chronic inflammation and infections are involved in the development and progression of atherosclerotic vascular disease.To evaluate the association between periodontitis and early atherosclerosis.Fifty-three subjects who received periodontal treatment and regular maintenance for at least 10 years, and 55 subjects with periodontitis but without a history of periodontal treatment were studied. Carotid artery intima-media wall thickness (CIMT) was measured with high-resolution B-mode ultrasonography. A blood sample was obtained to measure high sensitivity C-reactive protein, fibrinogen, lipoprotein cholesterol, leukocyte count and erythrocyte sedimentation rate. Covariates included age, gender, smoking, level of education, body mass index and physical activity. The benzoyl-DL-arginine-naphthylamide (BANA) test was used to determine the number of periodontal sites with periodontal pathogens.CIMT value was significantly higher in subjects with periodontitis than those without it (0.775 ± 0.268 and 0.683 ± 0.131 mm respectively, p = 0.027). C-reactive protein, leukocyte count and percentage of sites with periodontal pathogens were also significantly higher in subjects with periodontitis. Regression analysis identified age, periodontitis, and smoking as independent predictors of CIMT.These results suggest that untreated periodontitis is associated with early atherosclerotic carotid lesions and higher levels of inflammatory markers.

Association between atherosclerosis and periodontitis

Chronic inflammation and infections are involved in the development and progression of atherosclerotic vascular disease. To evaluate the association between periodontitis and early atherosclerosis. Fifty-three subjects who received periodontal treatment and regular maintenance for at least 10 years, and 55 subjects with periodontitis but without a history of periodontal treatment were studied. Carotid artery intima-media wall thickness (CIMT) was measured with high-resolution B-mode ultrasonography. A blood sample was obtained to measure high sensitivity C-reactive protein, fibrinogen, lipoprotein cholesterol, leukocyte count and erythrocyte sedimentation rate. Covariates included age, gender, smoking, level of education, body mass index and physical activity. The benzoyl-DL-arginine-naphthylamide (BANA) test was used to determine the number of periodontal sites with periodontal pathogens. CIMT value was significantly higher in subjects with periodontitis than those without it (0.775 ± 0.268 and 0.683 ± 0.131 mm respectively, p = 0.027). C-reactive protein, leukocyte count and percentage of sites with periodontal pathogens were also significantly higher in subjects with periodontitis. Regression analysis identified age, periodontitis, and smoking as independent predictors of CIMT. These results suggest that untreated periodontitis is associated with early atherosclerotic carotid lesions and higher levels of inflammatory markers.

Effect of rimonabant on carotid intima–media thickness (CIMT) progression in patients with abdominal obesity and metabolic syndrome: the AUDITOR Trial

ObjectiveThe aim of this trial was to determine whether obese patients benefit from treatment with rimonabant in terms of progression of carotid atherosclerosis. Rimonabant, a selective cannabinoid-1 receptor blocker, reduces...

Predictors of anterior and posterior wall carotid intima media thickness progression in men and women at moderate risk of coronary heart disease

The rate of carotid intima media thickness (CIMT) progression has been widely used in clinical trials as a surrogate marker for subclinical atherosclerosis. The aim of this study was to investigate relationships between coronary heart disease (CHD) risk markers and progression of CIMT in patients at moderate CHD risk. Participants included men (45-75 years) and women (55-74 years) in the control arm of a clinical trial. All had at least one major CHD risk factor and baseline posterior wall CIMT 0.7-2.0 mm, without significant stenosis. Posterior (n = 134) and anterior wall (in a subset, n = 72) CIMT were assessed with B-mode ultrasound at baseline and 12 and ∼18 months. Fasting lipoprotein lipid, apolipoprotein (Apo), inflammatory, and oxidative stress markers were evaluated. Baseline CIMT was inversely associated (P < .001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of anterior wall CIMT progression in linear regression analyses included glucose (P = .044), high-density lipoprotein cholesterol (HDL-C, inverse, P = .006), triglycerides (TG, P = .006), and ratios of total cholesterol (TC)/HDL-C (P = .013), TG/HDL-C (P = .005), and Apo B/HDL-C (P = .021). Posterior wall CIMT progressed on average, whereas anterior wall CIMT regressed (0.0078 vs -0.0164 mm/year, P = .014). Significant baseline CIMT-adjusted predictors of posterior wall CIMT progression included TC (P = .028), low-density lipoprotein-C (P= .035), non-HDL-C (P = .004), TG (P = .016), Apo B (P = .005), and ratios of TC/HDL-C (P < .001), TG/HDL-C (P = .015), Apo B/Apo AI (P = .012) and Apo B/HDL-C (P = .004). The strongest predictors for CIMT progression in anterior and posterior walls were lower baseline CIMT, increased TG, and elevated ratios, including TC/HDL-C, TG/HDL-C and Apo B/HDL-C.

Correlation between endothelial function and carotid atherosclerosis in rheumatoid arthritis patients with long-standing disease

IntroductionIn this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident cardiovascular (CV) disease.MethodsOne hundred eighteen patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA, had no history of CV disease and had at least one year of follow-up after disease diagnosis were randomly selected. Brachial and carotid ultrasonography were performed to determine FMD and carotid IMT, respectively.ResultsCarotid IMT values were higher and FMD percentages derived by performing ultrasonography were lower in individuals with a long duration from the time of disease diagnosis. Patients with a disease duration ≤ 7 years had significantly lower carotid IMT (mean ± SD) 0.69 ± 0.17 mm than those with long disease duration (0.81 ± 0.12 mm in patients with ≥ 20 years of follow-up). Also, patients with a long disease duration had severe endothelial dysfunction (FMD 4.0 ± 4.0% in patients with disease duration from 14.5 to 19.7 years) compared with those with shorter disease duration (FMD 7.4 ± 3.8% in patients with disease duration ≤ 7 years). Linear regression analysis revealed that carotid IMT was unrelated to FMD in the whole sample of 118 patients. However, carotid IMT was negatively associated with FMD when the time from disease diagnosis ranged from 7.5 to 19.7 years (P = 0.02).ConclusionsIn patients with RA without CV disease, endothelial dysfunction and carotid IMT increased with the duration of RA. The association between FMD and carotid IMT values was observed only in patients with long disease duration.