Baseline cIMT Research Articles

Progression of subclinical atherosclerosis in subjects with rheumatoid arthritis and the metabolic syndrome

Background and aimsRheumatoid arthritis (RA) has been associated with an increased risk of atherosclerosis. We aimed to evaluate the progression of carotid intima media thickness (cIMT) in RA patients subject to a cardiovascular treat-to-target intervention. In addition, the presence of the metabolic syndrome (MetS) on cIMT outcomes was evaluated. MethodsWe performed a cohort analysis of FRANCIS, in which RA patients ≤70 years without CVD or diabetes mellitus were randomized for either a treat-to-target intervention or usual care concerning CVD risk factors. MetS was scored at baseline. ResultsThree-year data was available in 212 well-controlled RA patients. The treat-to-target intervention resulted in a lower cIMT progression over three years compared to the usual care. However, there was no difference in cIMT at three years between groups.MetS was present in 40.1% of RA patients. Baseline cIMT was significantly higher in RA patients with MetS compared to those without (0.619 (0.112) versus 0.557 (0.104) mm; p < 0.001). After three years, cIMT progression was comparable (0.043 (0.071) versus 0.043 (0.072) mm; p = 0.96). In RA patients with MetS, the presence of plaques increased over three years from 12.9% to 23.5% (p = 0.01).The type of intervention had no effect on cIMT progression in RA patients with MetS. However, in subjects without MetS, treat-to-target resulted in a lower progression. ConclusionsRA patients with MetS showed an increased CVD risk profile based on both a higher prevalence of CVD risk factors and structural vascular changes. A treat-to-target approach of CVD risk factors reduced cIMT progression only in RA patients without MetS.

Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Background and aimsIncreased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. MethodsWe studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. ResultsWe identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. ConclusionsWe identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.

Indicators of Cardiovascular Risk in Metabolic Syndrome: Long Term Follow-up in Italian Patients.

Cardiovascular risk (CV) factors associated with the metabolic syndrome (MetS) may vary in different populations. In some, hypertension may be the major determinant, in others are low high-density lipoprotein cholesterol (HDL-C), high triglycerides, or another component. Subjects included in this analysis were identified in 2006, among those attending the Lipid Clinic of the Niguarda Hospital, and followed up through to 2013. Patient characteristics (including the occurrence of CV events) were obtained from electronic medical records. MetS was diagnosed according to the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) guidelines. The carotid intima media thickness (cIMT) was also followed in these patients over the years. After 7 years a total of 858 subjects had a complete follow-up; 271 of those had MetS. Patients developing a CV event showed elevated baseline cIMT (e.g. cIMTmax ≥ 2.4 mm in males and ≥ 2.2 mm in females); moreover the cIMT in MetS patients was higher at baseline and the rise over 7 years was larger compared with patients without MetS. By examining each body variable for MetS we found that a waist to height ratio (WHtR) ≥ 0.5 was present in nearly all subjects with a CV event. The follow-up data of a series of Italian patients with and without MetS, clearly indicates that the former have a raised cIMT and their arterial IMT progression is greater and the presence of a larger WHtR is apparently linked to a higher incidence of CV events.

Abstract 13512: Chemokines and Carotid Intima-Media Thickness in a European Population at High Risk for Cardiovascular Events: Results From the IMPROVE Study

Background: Experimental studies indicate that two archetype chemokines circulating in the blood, IL-8 and GRO-α, are critical for atherogenesis. However, their association with measures of subclinical atherosclerosis has not been investigated. Hypothesis: Here we test the hypothesis that circulating IL8 and GRO-α protein are associated with the carotid artery intima media thickness (c-IMT) in a large European multicenter study: the c-IMT and c-IMT Progression as Predictors of Vascular Events in a High Risk European Population ( IMPROVE ) study . Methods: IMPROVE study participants (n=3,703), recruited in 5 European Countries (Sweden, Finland, the Netherlands, France and Italy), had at least three cardiovascular (CV) risk factors but not prevalent CV diseases. C-IMT measures (mm) (c-IMT mean , c-IMT max and c-IMT mean-max ) were recorded at baseline. Each measurement represent the average of 8 (4 left and 4 right) carotid segments. IL8 and GRO-α were measured in plasma from 3,452 participants (women, n=1,784; men, n=1,668) using the Olink ProSeek CVD array I and expressed in arbitrary units. We evaluated the association, expressed as beta coefficient (β) and 95% confidence intervals (CI), between chemokines and c-IMT using median regression. Models were adjusted by sex, age, body mass index, hypertension, diabetes, current smokers, hypercholesterolemia and latitude. Results: Higher levels of IL8 and GRO-α were observed in participants from Northern Europe as compared to those from Southern Europe [IL8: 50 (41-62) vs 36 (28-49) and GRO-α 108 (70-176) vs 42(22-95)]. At multivariable analysis only in men, levels of IL8 were positively associated with c-IMT measures: c-IMT mean [1.0 x 10 -4 (6.5 x 10 -5 -1.4 x 10 -4 ), p&lt;0.01], c-IMT max [(6.5 x 10 -4 ,(4.8 x 10 -4 -8.2 x 10 -4 ), p&lt;0.01] and c-IMT mean-max [1.7 x 10 -4 , (1.3 x 10 -4 -2.2 x 10 -4 ), p&lt;0.01]. No corresponding association was observed for GRO-α and c-IMT measurements. Conclusions: The chemokine IL8, but not GRO-α, was associated with baseline c-IMT in men at high risk of CV events. Furthermore, our results suggest the presence of a European north-to-south gradient in chemokine levels. New studies are warranted to disentangle potential differences between IL8 and CV risk across sexes.

The CD4/CD8 Ratio is Inversely Associated with Carotid Intima-Media Thickness Progression in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Treatment.

Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 ± 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc, and 2 (2.08%) just with nucleoside reverse transcriptase inhibitors. The mean of ART exposition was 6.9 ± 5.9 years. Twenty six (27%) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) were hypertensive, 4 (4.16%) had type 2 diabetes, 23 (23.9%) had dyslipidemia, and 31 (32.3%) were infected with hepatitis C virus. Baseline cIMT was significantly associated with age (rho = 0.497; p < .001), basal glucemia (rho = 0.323; p = .001), triglycerides (rho = 0.232; p = .023), Framingham risk score (rho = 0.324; p = .001), CD4/CD8 ratio (rho = -0.176; p = .05), and dyslipidemia (0.72 ± 0.16 mm vs. 0.63 ± 0.11 mm; p = .029). In multivariable analysis where cardiovascular risk factor and ART were included, cIMT progression was inversely associated with CD4/CD8 ratio [odds ratio (OR) = 0.283; confidence interval (95% CI) 0.099-0.809; p = .019]. In conclusion, the inversion of CD4/CD8 ratio in treated HIV-infected patients is independently associated with cIMT progression, a marker of coronary heart disease. Therefore, it might be clinically useful as predictor of cardiovascular events.

Time-related trends in variability of cIMT changes in statin trials.

This brief article provides complementary data supporting the results reported in “Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006” [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988–2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of lipid-lowering therapy and control of LDL-C that may have impacted the variability in the results of cIMT studies.

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers.

The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 μm (95% confidence interval [CI]: 1082-1287) and increased by 93 μm (95% CI: 25-161) and 108 μm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 μm per each 10-mmHg raise in SBP at 1 year and an increase of 39 μm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. Our findings emphasize the importance of focusing not only on smoking cessation among smokers, but to simultaneously control other CVRFs, particularly blood pressure, in order to prevent future cardiovascular disease.

The relationship between carotid intima-media thickness and carotid plaque in the Northern Manhattan Study.

Carotid intima-media thickness (cIMT) and carotid plaque (CP) are proposed biomarkers of subclinical atherosclerosis associated with stroke risk. Whether cIMT and CP are distinct phenotypes or single traits at different stages of atherosclerotic development is unclear. We explored the relationship between these markers in the population-based Northern Manhattan Study. We used high-resolution ultrasound and validated imaging protocols to study the cross-sectional (N=1788 stroke-free participants) and prospective relationship (N=768 with follow-up scan; mean years between examinations=3.5) between CP and cIMT measured in plaque-free areas. The mean age was 66±9 (40% male, 19% black, 17% white, 61% Hispanic). The mean baseline cIMT was 0.92±0.09mm, 0.94±0.09mm among the 58% with prevalent plaque, 0.90±0.08mm among the 42% without prevalent plaque (p<0.0001). Each 0.1mm increase in baseline cIMT was associated with a 1.72-fold increased odds of plaque presence (95%CI=1.50-1.97), increased plaque thickness (effect on the median=0.46mm, p<0.0001), and increased plaque area (effect on the median=3.45mm(2), p<0.0001), adjusting for demographics and vascular risk factors. Elevated baseline cIMT was associated with an increased risk of new plaque in any location at follow-up, but after adjusting for demographics and vascular risk factors this association was no longer present. No association was observed in carotid segment-specific analyses. Increased cIMT was associated with baseline prevalent plaque but did not predict incident plaque independent of other vascular risk factors. This finding suggests that increased cIMT is not an independent predictor of plaque development although these atherosclerotic phenotypes often coexist and share some common vascular determinants.

Plasma IL-5 concentration and subclinical carotid atherosclerosis

ObjectiveGenetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT). MethodsWe used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline. ResultsIL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women. ConclusionsOur results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease.

Beneficial effect of high dose statins on the vascular wall in patients with repaired aortic coarctation?

BackgroundCarotid intima–media thickness (CIMT) is a marker for atherosclerosis. Adult post-coarctectomy patients (CoA) demonstrate an increased cardiovascular risk and increased CIMT compared to controls. This study evaluates the effect of high dose statins on the change in CIMT and cardiovascular risk. MethodsWe designed a multicenter, prospective, randomized, open label trial with blinded endpoint (PROBE design) to evaluate the effect of three year treatment with atorvastatin 80mg on CIMT and cardiovascular risk. Primary endpoint was CIMT measured by B mode ultrasonography. Secondary endpoints were mortality and morbidity due to cardiovascular disease and serum lipids. Results155 patients (36.3±11.8years, 96 (62%) male) were randomized (atorvastatin=80, no treatment=75). There was no significant effect of atorvastatin on the change in CIMT (treatment effect −0.005, 95% CI, −0.039–0.029; P=0.76). A significant effect on serum cholesterol and LDL levels was found (− 0.71, 95% CI, − 1.16 to − 0.26; P = 0.002 vs − 0.66, 95% CI − 1.06 to − 0.26; P = 0.001). There was no difference in secondary outcome measures. Baseline CIMT was higher in hypertensive compared to normotensive CoA. (0.69±0.16mm vs 0.61±0.98mm; P=0.002). Hypertension (ß=0.043, P=0.031) was the strongest determinant CIMT. ConclusionThree year treatment with atorvastatin does not lead to a reduction of CIMT and secondary outcome measures, despite a decrease in total cholesterol and LDL levels. Hypertensive CoA demonstrate the highest CIMT and the largest CIMT progression. Blood pressure control should be the main focus in CoA to decrease cardiovascular risk.

Atherosclerosis progression in patients with autosomal dominant hypercholesterolemia in clinical practice

Autosomal dominant hypercholesterolemias (ADH) are associated with high risk of premature cardiovascular disease (CVD). No data on progression of atherosclerosis in ADH population in clinical practice are available. To investigate atherosclerosis progression in ADH patients and its relationship with CVD risk factors. A total of 463 patients, 279 with familial hypercholesterolemia and 184 with familial combined hyperlipidemia, were prospectively followed during a median of 36.5 months. Carotid intima-media thickness (cIMT) was assessed at baseline and at the end of the follow-up by ultrasonography. A total of 259 patients (55.9%) showed cIMT progression and 149 (32.2%) remained within normal age-adjusted cIMT. Baseline cIMT was the variable most inversely associated with cIMT progression (B = -0.313; P < .001). Hypertension, diabetes, and smoking during follow-up were variables positively associated with progression. Patients who began statin treatment during the study period had less progression than former statin users. The 83.7% of ADH with normal baseline cIMT, absence of major CVD risk factors and non-high-density lipoprotein (HDL) cholesterol <190 mg/dL at follow-up remained with normal cIMT at the end of the study. Non-HDL cholesterol concentration reached during the follow-up was associated with cIMT only in subjects with abnormal cIMT at baseline. In this subgroup, cIMT tended to avoid progression with non-HDL cholesterol <130 mg/dL. Atherosclerosis progression varies greatly among ADH patients. cIMT progression was inversely related to baseline cIMT and previous use of statins, and positively with age and CVD risk factors during the follow-up. Patients previously treated with statins may not be the preferred candidates for atherosclerosis regression trials. Treatment recommendations in ADH should be based on baseline risk.

Do subclinical vascular abnormalities precede impaired physical ability and ADL disability?

Cardiovascular disease is an important cause of disability in activities of daily living (ADL) through its effect on physical functioning. However, it is unclear whether subclinical vascular abnormalities and rate of change in subclinical vascular abnormalities is also associated with an impaired physical ability and with ADL disability. In a longitudinal study, 490 middle-aged and older persons were included. Physical ability was measured using the Short Physical Performance Battery and ADL disability using a questionnaire on self-reported basic and instrumental ADL. Subclinical vascular abnormalities were measured by pulse wave velocity (PWV) and carotid intima media thickness (CIMT, in men only). Longitudinal associations between baseline markers of subclinical vascular abnormalities, their rate of change, and change in physical ability or ADL disability were assessed using generalized estimation equation models. After adjustment for confounders, higher baseline PWV, change in PWV, baseline CIMT (in men) and change in CIMT (in men) were associated with a higher rate of change in physical ability (regression coefficients 0.035, 95% CI [0.018; 0.052]; 0.047, 95% CI [0.024; 0.069]; 0.214, 95% CI [0.070; 0.358] and 0.148, 95% CI [0.019; 0.277], respectively). No relations were found for change in ADL disability. In subjects with incident cardiovascular disease, higher change in PWV was associated with a higher rate of change in ADL disability (regression coefficient 0.054, 95% CI [0.001; 0.106]). The present study showed that subclinical vascular abnormalities and rate of change were associated with higher rate of change in physical ability. The association between (change in) subclinical vascular abnormalities and ADL disability tended to be stronger in persons with incident and prevalent cardiovascular disease. These data may suggest that ADL decline is more a direct effect of experienced clinically manifest vascular events rather than the effect of progression of subclinical vascular abnormalities.

Baseline CD4(+) T-cell count and cardiovascular risk factors predict the evolution of cognitive performance during 2-year follow-up in HIV-infected patients.

The aim of our study was to better understand the dynamics between cardiovascular risk factors and immunological parameters in the evolution of cognitive performance in HIV+ patients. We conducted a prospective longitudinal study, consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits at two clinical centres. At baseline and after 2 years, all patients underwent a comprehensive neuropsychological battery. Common carotid intima-media thickness (cIMT) was also measured. A total of 150 patients completed the study (77% males, median age 46 years, 20% with past AIDS-defining events, 95% on cART, 88% with HIV-RNA<50 copies/ml). After a 2-year follow-up, there was no difference in the proportion of patients with cognitive impairment (32% versus 33% at baseline; P=1.00). However, a significantly worse memory performance was observed (z score mean change -0.51, sd 1.05; P=0.001). At multivariate analysis, baseline dyslipidaemia (OR 2.7, 95% CI 1.1, 7.1; P=0.037) showed a significant association with a higher risk of memory impairment at 2-year follow-up, while higher baseline CD4(+) T-cell count (OR 0.80 per 100 cells/μl higher; 95% CI 0.66, 0.97; P=0.026) was found to be a protective factor, adjusting for the presence of a memory impairment at baseline. When the analysis was restricted to patients who did not change antiretroviral therapy during the study period (n=109), baseline cIMT (OR 14.6 per 0.1 mm higher; 95% CI 1.1, 189.9; P=0.041) also emerged as an independent risk factor for memory impairment at 2-year follow-up. Immunological parameters and cardiovascular risk factors are independently associated with the evolution of cognitive status in HIV+ patients.

Abstract P340: Associations between Subclinical Carotid Atherosclerosis and Future Risk of Abdominal Aortic Aneurysm: the Atherosclerosis Risk in Community (ARIC) Study

Background: Abdominal aortic aneurysm (AAA) is a potentially lethal vasculopathy that shares multiple risk factors with conventional atherosclerotic disease, including advanced age, male sex, hypertension, and smoking. However, it is still debated whether subclinical atherosclerosis is an independent risk factor for AAA. Hypothesis: Subclinical carotid atherosclerosis is positively associated with future risk of AAA, independent of shared cardiovascular risk factors. Methods: We included 15,363 ARIC participants (74% whites) who had measures of carotid ultrasound at baseline (1987-89) at 45-64 years of age. Carotid intima-media thickness (cIMT) was measured bilaterally in the common carotid artery, carotid bifurcation, and internal carotid artery. Mean cIMT was estimated by combining the averages of cIMT measures at the 6 carotid sites. The presence of atherosclerotic plaque at any of the 6 segments was defined based on wall thickness ≥1.5 mm, or the presence of luminal encroachment or irregular intimal surface, or characteristics of arterial wall structural heterogeneity. Clinical AAAs were ascertained through hospital discharge diagnoses and death certificates through 2010. We used Cox proportional hazard models to examine the association between baseline carotid ultrasound measures and subsequent occurrence of clinical AAA. Results: In the total study sample (age 54±6 years, 45% men), the median (25 th to 75 th percentiles) cIMT at baseline was 0.71 (0.62 to 0.82) mm. Over an average of 21 years of follow up, a total of 392 clinical AAAs (74% male and 85% Whites) were ascertained. After adjustment for age, sex and race, participants in the highest quartile of baseline cIMT had 2.25 times higher risk of AAA (95% CI: 1.81, 2.79) compared to those in the lower 75 percentile. The presence of carotid atherosclerotic plaque at baseline was associated with 1.77 times increased risk of AAA (95% CI: 1.44, 2.17) after adjustment for age, sex and race. The associations for cIMT and atherosclerotic plaque remained significant after additional adjustment for baseline height, pack-years of smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and hypertension: HR=1.66 (95% CI: 1.32, 2.08) for cIMT quartile 4 vs lower 75 percentile and 1.34 (95% CI: 1.08, 1.66) for presence of carotid atherosclerotic plaque. Further exclusion of participants with history of coronary heart disease or stroke at baseline slightly attenuated but did not abolish the associations of cIMT and atherosclerotic plaque with AAA (p&lt;0.05 after the exclusions). Conclusion: Our study findings suggest that subclinical carotid atherosclerosis in middle-age is independently associated with future risk of clinical AAA.

Carotid intima-media thickness progression predicts cardiovascular events in Japanese patients with type 2 diabetes

AimsThe aim of this retrospective study was to investigate the relationship between progression of carotid intima-media thickness (cIMT) and cardiovascular events in Japanese patients with type 2 diabetes mellitus (T2DM) and free of history of cardiovascular events. MethodsPatients with T2DM (n=342) without history of cardiovascular events whose cIMT was assessed more than twice by ultrasonography were recruited and followed up for cardiovascular events. ResultsDuring a mean follow-up of 7.6 years, 56 (16.4%) cardiovascular events (27 coronary events and 29 cerebrovascular events) were recorded. Multivariate analysis with the Cox proportional hazard model identified cIMT progression as a significant determinant of cardiovascular events, with a hazard ratio (HR) of 2.24 (95% confidence interval; CI, 1.25–4.03, P<0.01), in addition to baseline cIMT. The Kaplan–Meier curves also showed significantly higher event rate in patients with high cIMT progression compared with those with low cIMT progression (log-rank χ2=6.65; P<0.01). Furthermore, the combination of high baseline cIMT and high cIMT progression was a significant predictor of cardiovascular events. ConclusionOur findings suggest that cIMT progression, in addition to baseline cIMT, is a predictor of cardiovascular events in patients with T2DM without history of cardiovascular events, and that the combination of cIMT progression and baseline cIMT has a strong predictive power for such events.

Atherosclerosis and physical functioning in older men, a longitudinal study.

Functional decline is a major threat to independency, progressing into functional limitations and eventually leading to disability. Chronic diseases, especially cardiovascular diseases, are important determinants of functional limitations and disability. Vascular damage exits long before it is clinically manifest and can have adverse effects on health, physical and cognitive functioning. The objective was to investigate the association between non-invasive atherosclerosis measures and physical functioning in older men. Prospective cohort study. The study was conducted in the general community. 195 independently living older men. Atherosclerosis was measured by intima media thickness (CIMT) of the common carotid artery using ultrasonography and assessment for presence of atherosclerotic plaques. Physical functioning was measured by isometric handgrip strength and leg extensor strength using a hand held dynamometer, lower extremity function using the physical performance score and ability to perform activities of daily life using the modified Stanford health assessment questionnaire. Linear regression analysis was performed to estimate the associations between CIMT or plaques and physical functioning. After adjustment for confounders, higher baseline CIMT was associated with lower isometric handgrip strength at follow up (βCIMT = -7.21, 95% CI[-13.64;-0.77]). No other associations were found between CIMT and physical functioning. In addition, no associations were found for the presence of plaques and physical functioning either at baseline, or at follow-up. Atherosclerosis, as measured by higher CIMT, is related to a lower isometric handgrip strength at follow-up, but no further associations with physical functioning were found in this longitudinal study among independently living older men.

Carotid Plaque Burden as a Measure of Subclinical Atherosclerosis: Comparison With Other Tests for Subclinical Arterial Disease in the High Risk Plaque BioImage Study

The purpose of this study was to compare carotid plaque burden, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and abdominal aortic diameter (AAD) to coronary artery calcium score (CACS) in people without known cardiovascular disease. The clinical utility of risk factors to predict cardiovascular events is limited. Detection of subclinical atherosclerosis by noninvasive tests such as CACS, cIMT, carotid plaque burden, AAD, and ABI may improve risk prediction above that of established risk scoring models, namely, Framingham Risk Score. The High Risk Plaque BioImage study investigated 6.101 asymptomatic persons and reports baseline CACS, cIMT, ABI, and AAD. In addition, we present findings from a new 3-dimensional-based ultrasound approach, where the carotid artery was investigated in cross section from proximal in the neck to as distal as possible. From the resulting 10-s video, plaque was outlined on cross-sectional images and all plaque areas were summarized into "plaque burden." The mean age was 68.8 years, and 65.3% of subjects had intermediate Framingham Risk Score (6% to 20% 10-year risk). Carotid plaques were identified in 78% of cases, abnormal ABI in 10%, AAD >20 mm in 28%, and coronary calcium in 68% of participants. Carotid plaque burden was found to correlate stronger with CACS (chi-square 450, p < 0.0001) than did cIMT (chi-square 24, p < 0.0001), AAD (chi-square 2.9, p = 0.091), and ABI (chi-square 35.2, p < 0.0001). In the BioImage study, a new 3-dimensional-based ultrasound method identified more carotid plaques than in previous studies. Compared to other methods, carotid plaque burden was the strongest cross-sectional predictor of CACS, and its clinical utility as predictor of future cardiovascular events is being evaluated in the BioImage study. (BioImage Study: A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population; NCT00738725).

Effects of Smoking and Cessation on Subclinical Arterial Disease: A Substudy of a Randomized Controlled Trial

BackgroundThe mechanisms by which smoking cessation reduces cardiovascular disease risk are unclear. We evaluated longitudinal changes in carotid intima-media thickness among current smokers enrolled in a prospective, randomized smoking cessation clinical trial.Methodology/Principal FindingsSubjects were enrolled in a randomized, double-blind, placebo-controlled trial of 5 smoking cessation pharmacotherapies and underwent carotid ultrasonography with carotid intima-media thickness measurement. Subjects were classified as continuously abstinent (biochemically confirmed abstinence at 6 months, 1 year, and 3 years post-quit attempt), intermittently abstinent (reported smoking at one of the three time points), or smoked continuously (reported smoking at all three time points). The primary endpoint was the absolute change (mm) in carotid intima-media thickness (ΔCIMTmax) before randomization and 3 years after the target quit date. Pearson correlations were calculated and multivariable regression models (controlling for baseline CIMTmax and research site) were analyzed. Among 795 subjects (45.2±10.6 years old, 58.5% female), 189 (23.8%) were continuously abstinent, 373 (46.9%) smoked continuously, and 233 (29.3%) were abstinent intermittently. There was a greater increase in carotid intima-media thickness among subjects who were continuously abstinent than among those who smoked continuously (p = 0.020), but not intermittently (p = 0.310). Antihypertensive medication use (p = 0.001) and research site (p<0.001) independently predicted ΔCIMTmax – not smoking status. The greatest increase in carotid intima-media thickness among continuous abstainers was related to increases in body-mass index (p = 0.043).Conclusions/SignificanceSmoking status did not independently predict ΔCIMTmax; increasing body-mass index and antihypertensive medication use were the most important independent predictors. The rapid reduction in cardiovascular disease events observed with smoking cessation is unlikely to be mediated by changes in subclinical atherosclerosis burden.Trial RegistrationClinicalTrials.gov NCT00332644

Use of annual ABPM, and repeated carotid scan and echocardiography to monitor cardiovascular health over nine yr in pediatric and young adult renal transplant recipients

In adult hypertensive patients, increased cIMT and LVH are independent risk factors for cardiovascular events. We have previously observed that in pediatric RTRs with tight control of BP, cIMT did not progress over time. This investigation is an extension of the aforementioned study aimed at re-examining cIMT and also reporting serial echocardiography results. Twenty-two RTRs aged 9.4 ± 3.3 yr at their baseline carotid scan underwent two additional vascular ultrasounds during a follow-up of 9.1 ± 0.9 yr. Carotid scan and echocardiography examinations were carried out simultaneously with ABPM. Antihypertensive therapy was determined according to the recipient's ABPM results, which were performed at yearly intervals. Baseline cIMT was significantly greater in RTRs than in healthy controls. There was no statistical evidence of systematic changes in cIMT over time. At the last examination, 14 of 17 RTRs with treated hypertension had controlled hypertension (prevalence 82%; 95% CI, 56.5-96.2), and the overall prevalence of LVH was 4.5% (95% CI, -0.01 to 23.5). The lack of progression of cIMT over time and the low prevalence of LVH might reflect the effect of long-standing BP control.

Automated Edge Detection Versus Manual Edge Measurement in Analysis of Brachial Artery Reactivity: A Comparison Study

High resolution ultrasound, combined with computer imaging technology, is commonly used to measure changes in brachial artery diameter for the determination of endothelial-dependent vasodilation (EDD) and endothelial independent-vasodilation (EID). Currently, two methods of computerized edge-detection systems are in use to measure changes in artery diameter. One system involves the sonographer manually tracking the artery walls while the second system involves a computer automated edge-detection system that automatically tracks the artery wall. The purpose of this study was to compare the two types of computerized edge-detection systems for measuring vascular function and structure. One hundred fifty (female = 70, male = 80) participants agreed to participate. Baseline brachial diameter, carotid intima-medial thickness (cIMT), EDD and EID were measured by the two computerized edge-detection systems utilizing the same ultrasound B-mode image. Mean values (±standard error) for baseline diameter, cIMT, EDD and EID were 3.53 (±0.10) mm, 0.43 (±0.01) mm, 5.72 (±0.20)% and 22.17 (±0.60)%, respectively for the manual edge-detection software system. Mean values for baseline diameter, cIMT, EDD and EID were 3.59 (±0.10) mm, 0.44 (±0.01) mm, 7.33 (±0.30)% and 25.77 (±0.60)%, respectively for the automated edge-detection software system. Bland-Altman plots displayed large variations between the two edge-detection methods for assessing cIMT and changes in artery diameter following brachial EDD and EID. The results of the study demonstrate that manual and automated computerized edge-detection systems track dynamic changes in brachial artery diameter and cIMT measures differently. Therefore, caution should be used when comparing research utilizing different computerized edge-detection systems for measuring vascular function and structure. (E-mail: will0188@umn.edu)