cIMT Progression Research Articles

Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?

The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Meta-analysis of individual participant data. From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

Polymorphisms of the PPAR-γ (rs1801282) and Its Coactivator (rs8192673) Have a Minor Effect on Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

Background. The present study was designed to clarify whether common single nucleotide polymorphisms (SNPs) of the Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene (rs1801282) and the Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 (PGC-1α) gene (rs8192673) are associated with markers of carotid and coronary atherosclerosis in Caucasians with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled in the cross-sectional study. Markers of carotid atherosclerosis were assessed ultrasonographically. In 215 out of 595 subjects with T2DM, a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of either rs1801282 or rs8192673 was performed using KASPar assays. Results. In our study, we demonstrated an effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM in univariate and in multivariable linear regression analyses. Finally, we did not demonstrate any association between either rs1801282 or rs8192673 and markers of coronary atherosclerosis. Conclusions. In our study, we demonstrated a minor effect of the rs1801282 on markers of carotid atherosclerosis (presence of plaques) in Caucasians with T2DM. Moreover, we demonstrated a minor effect of the rs8192673 on CIMT progression in the 3.8-year follow-up in Caucasians with T2DM.

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Polymorphisms rs699 and rs4762 of the Angiotensinogen Gene and Progression of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

Background: The aim of the study was to investigate the association between two polymorphisms of the angiotensinogen (AGT) gene (rs699 and rs4762) and subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). Patients and methods: In this cross-sectional study 599 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled. The CIMT and plaque characteristics (presence/absence and plaque thickness) on both the near and the far walls in the common carotid artery, bulb and internal carotid arteries, bilaterally were assessed ultrasonographically. After several years (3.8 ± 0.5 years), patients were re-assessed and changes in subclinical markers of carotid atherosclerosis were calculated. Polymorphisms rs699 and rs4762 of the AGT gene were genotyped by using allele-specific PCR (KASPar) assay. Results: The highest increase in carotid plaque thickness was observed in homozygote carriers of the A allele, even after adjustment for confounding variables. Polymorphism rs699 did not affect the progression of CIMT in the increase of number of segments with plaques. Conclusions: In the study we have found that the rs699 of the AGT gene is a potential genetic marker of carotid atherosclerosis progression (expressed as increase in carotid plaque thickness) in Slovenian patients with T2DM. It did not affect other ultrasonographic markers of carotid atherosclerosis progression. Polypmorphism rs4762 was not associated with carotid atherosclerosis progression in Slovenian patients with T2DM.

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.

Abstract 12216: Age-Related Macular Degeneration as a Predictor of Incidence and Progression of Subclinical Cardiovascular Disease and Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis

Introduction: Age-related macular degeneration (AMD) is a leading cause of vision loss in US adults and shares many similarities with CVD pathophysiology. Hypothesis: We assessed the hypothesis that the presence of AMD would independently predict the incidence and progression of subclinical CVD and CVD events in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: Our cohort consisted of 5,803 adults free of known CVD who had retinal photographs taken during the first follow-up examination of the MESA (Exam 2; Aug 2002-Jan 2004). Photographs were evaluated for AMD using the Wisconsin age-related maculopathy grading system. Coronary artery calcium (CAC), carotid intima-media thickness (cIMT), ankle brachial index (ABI), and brachial artery flow-mediated dilation (FMD) were assessed at baseline (Exam 1; July 2000-Aug 2002). Changes in CAC and cIMT from Exam 1 were determined at follow-up Exam 5 (April 2010-Dec 2011). Incident CVD events were ascertained from 2002 through 2012. Results: Participants were categorized as AMD+ (n = 244) or AMD- (n = 5,559). Groups did not differ at baseline for cIMT, ABI, or FMD (P>0.19). At Exam 5, 92 AMD+ and 2684 AMD- participants had CAC scores. In those with CAC = 0 at baseline, CAC incidence did not differ between AMD+ (n = 21) and AMD- groups (n = 761). In those with CAC>0, CAC progression was greater in the 46 AMD+ vs. the 1170 AMD- participants after a mean follow-up of 10.4 ± 2.4 years using multivariable-adjusted models (530 ± 537 vs. 339 ± 426 Agatston units, P = 0.004). Ten year cIMT progression (P = 0.85) and incident CVD events (multivariable-adjusted HR (95% CI) = 1.3 (0.9, 1.8); P = 0.20) did not differ between groups. Conclusions: In conclusion, the presence of AMD in a diverse population without known CVD was independently associated with higher 10-year CAC progression in participants with baseline CAC>0. AMD was not associated with CAC incidence, other subclinical CVD markers or CVD events. The association between AMD and CAC progression suggests that AMD is associated with a greater degree of atherosclerosis. Longer follow up of individuals with AMD is warranted to clarify whether greater CAC progression increases risk of CVD events.

Carotid intima-media thickness progression and risk of vascular events in people with diabetes: results from the PROG-IMT collaboration.

OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33–92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12–1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between −0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91–1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

Early initiation of statin treatment in children with familial hypercholesterolaemia.

This article provides recent insights on the early onset of atherosclerosis in heterozygous familial hypercholesterolemia and reports on novel treatment options as well as on the consequences of long-term statin use in childhood. Children with familial hypercholesterolemia have greater mean carotid intima-media thickness (cIMT) than their unaffected siblings even before the age of 8 years, which is several years earlier than previously reported. In those children, 2 years of rosuvastatin treatment resulted in slowing of the cIMT progression. In addition, in a 10-year follow-up study after a pravastatin intervention trial, long-term statin therapy in young adult familial hypercholesterolemia patients was associated with normalization of cIMT progression and appeared effective in prevention of very premature cardiovascular events. These effects were observed without untoward safety concerns. However, a majority of these young adults did not reach cholesterol goals according to general guidelines, indicating the need for improvement of treatment in this patient group. The importance, efficacy and safety of early initiation statin therapy in familial hypercholesterolemia children were further confirmed by recent findings. Nevertheless, to reach current treatment goals, the use of more potent statins is required and has been proven well tolerated and effective in young children.

AB068. Association between MTHFR C677T and carotid intima medial thickness progression in post-ischemic stroke patient

Background and objective Substitution of c.677C > T in methylenetetrahydrofolate reductase (MTHFR) gene contributes to increase blood level of homocysteine (Hcy). Hyperhomocysteinemia is believed to have association with vascular damage leads to atherosclerosis. Defect MTHFR may influence vascular progression in post ischemic stroke. Carotid intima media thickness (c-IMT) has been known as vascular marker for atherosclerosis and predictor for ischemic stroke. The study aims to determine association between MTHFR C677T and c-IMT progression in post-ischemic stroke patients.

49th Annual Meeting of the Association for European Paediatric and Congenital Cardiology, AEPC with joint sessions with the Japanese Society of Pediatric Cardiology and Cardiac Surgery, Asia-Pacific Pediatric Cardiology Society, European Association for Cardio-Thoracic Surgery and Canadian Pediatric Cardiology Association, Prague, Czech Republic, 20–23 May 2015

Background: This prospective study focuses on factors associated with arterial damage in children with type 1 diabetes (T1D). Materials and Methods: Eighty children and adolescents with T1D (mean age 15, range: 8-20 yrs; mean diabetes duration 7, range: 0.5 to 19 years) were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. HLA genotypes were determined in dried spots of peripheral blood by polymerase chain reaction followed by hybridization assay. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results: cIMT progression (% change of cIMT from baseline) correlated inversely with the % changes of both CAC (p = 0.04, r=−0.3, n=62) and FMD (p=0.03, r=−0.3, n=67). RTI frequency correlated significantly with cIMT progression irre- spective of age, diabetes duration, BMI, and HbA1c (p=0.03, r=0.3, in multivariate analysis). When patients were divided in relation to DQ2/8 genotype and RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with CRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions: Diabetes-risk genotype DQ2/8 and inflammation con- tribute to vascular changes in children and adolescents with T1D. (Less)

Long-term effects of an intensive intervention in HIV-infected patients with moderate-high atherosclerotic cardiovascular risk.

To evaluate the 5 year effects of an intensive intervention versus the standard-of-care intervention on cardiovascular risk factors in HIV-infected patients on antiretroviral therapy (ART). This was a longitudinal study including virologically suppressed patients with at least two cardiovascular risk factors or a Framingham risk score ≥10%. Intensive and standard-of-care interventions aimed for low-density lipoprotein cholesterol (LDL-C) <100 and <130 mg/dL, respectively, by using lipid-lowering drugs. In the intensive group, switching ART when needed to achieve the LDL-C target and low-dose aspirin were used. Achievement of LDL-C targets and changes in carotid intima-media thickness (cIMT) and cardiovascular biomarkers were compared between groups at different timepoints through a 5 year period. Twenty-two and 25 patients in the intensive and standard intervention groups, respectively, were followed up. At 5 years, pre-specified LDL-C targets were achieved in 82% (intensive) and 81% (standard of care) of patients. The median (IQR) change in LDL-C in the intensive and standard intervention groups was -78 (-96/-39.7) and -49 (-72/-3) mg/dL, respectively (P = 0.04), and in the Framingham score was -4% (-8%/-1%) and 0% (-4%/6.5%), respectively (P = 0.01). There were no significant intra- or between-group changes in cIMT measurements. A significant decrease was observed in the intensive and standard groups in interleukin 6 (P = 0.001 and P = 0.002, respectively) and in tumour necrosis factor α (P = 0.023 and P = 0.052, respectively). Asymptomatic creatine phosphokinase elevations were observed in two patients assigned to the standard intervention group. An intensive intervention on cardiovascular risk factors in HIV-infected patients on ART was feasible, safe and capable of achieving LDL-C targets in the long term. Both intensive and standard interventions were accompanied by antiatherosclerotic changes in inflammatory cytokines and lack of cIMT progression.

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.

SAT0133 Delayed Progression of Carotid Intima Media Thickness in Patients with Rheumatoid Arthritis: 1-Year Results of the FRANCIS Study

BackgroundRheumatoid arthritis (RA) is recognized as an independent cardiovascular risk factor. Guidelines for cardiovascular risk (CVR) management, advise aggressive treatment in RA. Tight treatment for CVR factors in RA is...

Effects of fenofibric acid on carotid intima-media thickness in patients with mixed dyslipidemia on atorvastatin therapy: randomized, placebo-controlled study (FIRST).

To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol, The Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) trial evaluated the effects of fenofibric acid (FA) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin. This multicenter, double-blind, placebo-controlled study was performed in patients with mixed dyslipidemia (fasting triglycerides, ≥150 mg/dL; high-density lipoprotein cholesterol, ≤45 [men] or 55 mg/dL [women]; low-density lipoprotein cholesterol, ≤100 mg/dL once and averaging ≤105 mg/dL) and a history of coronary heart disease or risk equivalent. Patients on background atorvastatin (continued on starting dose or titrated to 40 mg, if needed) were randomized to FA 135 mg or placebo. The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT, measured by ultrasound. In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy, rate of change in posterior-wall cIMT was similar with FA plus atorvastatin (-0.006 mm/y) versus atorvastatin monotherapy (0.000 mm/y; P=0.22). FA plus atorvastatin was favored (P<0.05) in 5 of 24 prespecified subgroups: age ≥60 years, history of coronary artery disease, cIMT >0.795 mm, triglycerides 170 to 235 mg/dL, and statin use at entry. Adverse events were consistent with the known safety profiles of both drugs; however, FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy (6.5% versus 0.9%). Compared with atorvastatin monotherapy, FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia.

Plasma autoantibodies against apolipoprotein B-100 peptide 210 in subclinical atherosclerosis

ObjectiveExperimental studies have suggested that autoimmunity is involved in atherosclerosis and provided evidence that both protective and pro-atherogenic immune responses exist. This concept has received support from small clinical studies implicating autoantibodies directed against apolipoprotein B-100 (apoB-100) in human atherosclerosis. We examined circulating autoantibodies directed against native and malondialdehyde (MDA)-modified epitope p210 of apoB-100 (IgG-p210nat and IgM-p210MDA) in relation to early atherosclerosis in a large, European longitudinal cohort study of healthy high-risk individuals. Approach and resultsIgG-p210nat and IgM-p210MDA were quantified in baseline plasma samples of 3430 participants in the IMPROVE study and related to composite and segment-specific measures of severity and rate of progression of carotid intima-media thickness (cIMT) determined at baseline and after 30 months. IgM-p210MDA autoantibody levels were independently related to several cIMT measures both in the common carotid artery and in the carotid bulb, including measures of cIMT progression, higher levels being associated with lower cIMT or slower cIMT progression. Consistent inverse relationships were also found between plasma levels of IgG-p210nat and baseline composite measures of cIMT. These associations disappeared when adjusting for established and emerging risk factors, and there were no associations with rate of cIMT progression besides in certain secondary stratified analyses. ConclusionsThe present study provides further evidence of involvement of autoantibodies against native and MDA-modified apoB-100 peptide 210 in cardiovascular disease in humans and demonstrates that these associations are present already at a subclinical stage of the disease.

Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial

Metformin reduces cardiovascular risk in patients with type 2 diabetes seemingly independent of lowering blood glucose concentration. We assessed the cardiovascular effects of metformin in individuals without type 2 diabetes. We did a single-centre, double-blind, placebo-controlled trial at the Glasgow Clinical Research Facility (Glasgow, UK). We enrolled patients taking statins who did not have type 2 diabetes but who did have coronary heart disease and large waist circumferences. Participants were randomly assigned (1:1) by computer to either metformin (850 mg twice daily) or matching placebo in block sizes of four. Patients, investigators, trial staff, and statisticians were masked to treatment allocation. The primary endpoint was progression of mean distal carotid intima-media thickness (cIMT) over 18 months in the modified intention-to-treat population. Secondary endpoints were changes in carotid plaque score (in six regions), measures of glycaemia (HbA1c, fasting glucose, and insulin concentrations, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and concentrations of lipids, high sensitivity C-reactive protein, and tissue plasminogen activator. The trial was registered at ClinicalTrials.gov, number NCT00723307. We screened 356 patients, of whom we enrolled 173 (86 in the metformin group, 87 in the placebo group). Average age was 63 years. At baseline, mean cIMT was 0·717 mm (SD 0·129) and mean carotid plaque score was 2·43 (SD 1·55). cIMT progression did not differ significantly between groups (slope difference 0·007 mm per year, 95% CI -0·006 to 0·020; p=0·29). Change of carotid plaque score did not differ significantly between groups (0·01 per year, 95% CI -0·23 to 0·26; p=0·92). Patients taking metformin had lower HbA1c, insulin, HOMA-IR, and tissue plasminogen activator compared with those taking placebo, but there were no significant differences for total cholesterol, HDL-cholesterol, non-HDL-cholesterol, triglycerides, high sensitivity C-reactive protein, or fasting glucose. 138 adverse events occurred in 64 patients in the metformin group versus 120 in 60 patients in the placebo group. Diarrhoea and nausea or vomiting were more common in the metformin group than in the placebo group (28 vs 5). Metformin had no effect on cIMT and little or no effect on several surrogate markers of cardiovascular disease in non-diabetic patients with high cardiovascular risk, taking statins. Further evidence is needed before metformin can be recommended for cardiovascular benefit in this population. Chief Scientist Office (Scotland).

The association between carotid intima media thickness and individual dietary components and patterns

AimsTo review: 1) the correlation between individual dietary components and carotid intima media thickness (cIMT); 2) the relationship between dietary patterns and cIMT; 3) the effect of dietary interventions on cIMT progression. Data synthesisAn electronic search for epidemiological and intervention trials investigating the association between dietary components or patterns of intake and cIMT was performed in PUBMED, EMBASE and the Cochrane Library. Epidemiological data shows that a higher intake of fruit, wholegrains and soluble fibre and lower consumption of saturated fat in favour of polyunsaturated fat is associated with lower cIMT. In people at high risk of cardiovascular disease >93 g/day of fruit is associated with lower cIMT. Lower cIMT has also been observed when >0.79 serves/day of wholegrains and >25 g/day of fibre, predominately in the soluble form is consumed. Saturated fat is positively associated with cIMT, for every 10 g/day increase in saturated fat cIMT is 0.03 mm greater. Olive oil is inversely associated with cIMT, with a benefit seen when >34 g/day is consumed. While there are many epidemiological studies exploring the association between dietary intake and cIMT there are few intervention studies. Intervention studies show that a Mediterranean diet may reduce cIMT progression, especially in those with a higher cIMT. ConclusionsA Mediterranean style dietary pattern, which is high in fruits, wholegrains, fibre and olive oil and low in saturated fat, may reduce carotid atherosclerosis development and progression. However further research from randomised controlled trials is required to understand the association between diet and cIMT and the underlying mechanisms.

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.

FRI0134 Increased progression of carotid intima media thickness in thyroid peroxidase antibody positive rheumatoid arthritis patients

BackgroundCoexistence of autoimmune disorders was recently demonstrated for rheumatoid arthritis (RA) and hypothyroidism, and, interestingly, this coexistence amplifies the elevated cardiovascular risk in RA. Autoimmune hypothyroidism is characterised by the...