Surrogate Marker Of Atherosclerosis Research Articles

Study of serum adiponectin level as an atherosclerotic index in the elderly and its relationship to carotid intima–media thickness

Background It is well known that aging is associated with several hormonal alterations. However, the consequence of aging on the endocrine function of adipose tissue is not fully elucidated. Adiponectin is a new anti-inflammatory protein secreted exclusively by adipocytes and plays a protective role against insulin resistance and atherosclerosis.Aim of the work The aim of the work was to assess serum adiponectin as a biomarker for atherosclerosis and its relation to the carotid intima–media thickness (CIMT) as a clinical surrogate marker of atherosclerosis in elderly patients.Patients and methods The study was conducted on 80 participants aged 20–85 years who were subdivided into four groups. The first group was the control group (GI), which included 20 healthy young volunteers aged 20–40 years. The other three groups each included 20 elderly participants aged above 65 years who were classified according to arterial blood pressure and serum blood glucose levels into elderly healthy (GII), elderly hypertensives (GIII), and elderly diabetics (GIV).Results The mean adiponectin level (control, 12.48±3.95; GII, 9±3.25; GIII, 8.49±2.40; and GIV, 7.16±3.23) was significantly lower in individuals with high CIMT than in those with low CIMT (GI, 0.64±0.05; GII, 0.75±0.06; GIII, 0.72±0.08; GIV, 1.03±0.15). Adiponectin level was negatively correlated with age, BMI, systolic blood pressure, diastolic blood pressure, triglyceride, low-density lipoprotein cholesterol, and blood glucose, and positively correlated with high-density lipoprotein cholesterol.Conclusion Adiponectin was significantly negatively correlated with CIMT independently of age, sex, and all metabolic risk factors. The present study found that serum adiponectin level in humans is lower in elderly individuals and in patients with diabetes mellitus and essential hypertension than in healthy participants, and is negatively affected by the duration of these diseases.

Brief report: lack of replication of an association between anti-citrullinated fibrinogen and subclinical atherosclerosis in patients with rheumatoid arthritis.

Results of a recent study suggested that the excess cardiovascular (CV) risk observed in patients with rheumatoid arthritis (RA) could be partially explained by the presence of immune complexes of antibodies against citrullinated proteins that locally promote and perpetuate inflammation and progression of atherosclerotic plaques. The present study was undertaken to attempt to replicate one of the observations supporting this hypothesis, i.e., association between anti-citrullinated fibrinogen (anti-Cit-fibrinogen) positivity and subclinical atherosclerosis. Three surrogate markers of atherosclerosis were assessed in 124 RA patients with no previous history of CV events: carotid intima-media thickness (CIMT) assessed by carotid ultrasonography, carotid plaques assessed by carotid ultrasonography, and Coronary Artery Calcification Score (CACS) determined by multidetector computed tomography (CT) scanning. We analyzed the relationship of these 3 subclinical atherosclerosis markers to the presence and levels of autoantibodies, including anti-Cit-fibrinogen, anti-cyclic citrullinated peptide 2 (anti-CCP-2), and rheumatoid factor (RF). Carotid plaques and CIMT >0.90 mm were present in 69.4% and 15.3%, of the patients, respectively, and the CACS was moderate or high in 21.0%. None of these surrogate markers of atherosclerosis showed a significant association with positivity for or the level of anti-Cit-fibrinogen antibodies (either against the whole protein [present in 33.9% of the patients] or against an immunodominant peptide [present in 23.4%]), anti-CCP-2 (present in 60.7%), or RF (present in 58.1%) in this series of patients with RA. Our results do not support the notion that there is a relationship between anti-Cit-fibrinogen antibodies and subclinical atherosclerosis in RA, thus calling into question the claim that these antibodies have a role in the increased risk of CV disease observed in patients with RA.

Soluble RAGE and atherosclerosis in youth with type 1 diabetes: a 5-year follow-up study.

BackgroundAdvanced glycation end products (AGEs) play a role in the development of late complications and atherosclerosis in diabetes by engaging the receptor for advanced glycation end products, RAGE. Receptor binding leads to activation of the vascular endothelium and increased inflammation in the vessel wall. The soluble variants of the receptor, endogenous secretory RAGE (esRAGE) and the cleaved cell-surface part of RAGE, which together comprise soluble RAGE (sRAGE), are suggested to have a protective effect acting as decoys for RAGE. We aimed to test whether high levels of soluble variants of RAGE could be protective against atherosclerosis development.MethodsParticipants in the prospective atherosclerosis and childhood diabetes study were examined at baseline (aged 8–18) and at follow-up after 5 years. Both sRAGE and esRAGE were measured by immunoassay in 299 patients with type 1 diabetes and 112 healthy controls at baseline and 241 patients and 128 controls at follow-up. The AGEs methylglyoxal-derived hydroimidazolone-1 (MG-H1) and carboxymethyllysine (CML) were measured by immunoassay. The surrogate markers of atherosclerosis assessed were carotid intima-media thickness (cIMT), C-reactive protein (CRP) and Young’s modulus, measures of arterial wall thickness, inflammation and arterial stiffness, respectively.ResultsLevels of sRAGE and esRAGE correlated strongly both at baseline and at follow-up in both diabetes patients and controls. With increasing age, mean values of both variants declined, independent of gender, diabetes or pubertal stage. In the diabetes group, multiple regression analysis showed a positive association between both variants of soluble RAGE and cIMT. There was no significant relationship with Young’s modulus, but a negative association between sRAGE at baseline and CRP at follow-up. The ratios between the AGEs and the variants of soluble RAGE were increased in diabetes patients compared to controls.ConclusionsThe results show a possible protective effect of high levels of sRAGE at baseline against inflammation 5 years later, but not on arterial stiffness or wall thickness, in this cohort of adolescents and young adults with T1D.

Liraglutide improves carotid intima-media thickness in patients with type 2 diabetes and non-alcoholic fatty liver disease: an 8-month prospective pilot study

Objective: To explore the effects of the glucagon-like peptide-1 receptor analogue liraglutide on subclinical atherosclerosis in diabetic subjects with non-alcoholic fatty liver disease (NAFLD).Research design and methods: In this 8-month prospective study, 29 subjects with type 2 diabetes (T2DM) and NAFLD (16 men and 13 women, mean age: 61 ± 10 years) were matched for age and gender with 29 subjects with T2DM without NAFLD (16 men and 13 women, mean age: 61 ± 8 years). Liraglutide 0.6 mg/day for 2 weeks, followed by 1.2 mg/day, was given in addition to metformin.Main outcome measures: Anthropometric variables, glucometabolic parameters and carotid intima-media thickness (IMT) using B-mode real-time ultrasound were assessed at baseline and 4 and 8 months.Results: Glycated hemoglobin reduced significantly in both groups. No significant changes were found in body weight, waist circumference and lipids. Carotid IMT decreased significantly in the T2DM patients with NAFLD (from 0.96 ± 0.27 to 0.82 ± 0.17 to 0.85 ± 0.12 mm, p = 0.0325), but not in the T2DM patients without NAFLD (from 0.91 ± 0.23 to 0.88 ± 0.17 to 0.85 ± 0.15 mm, p = 0.4473).Conclusion: Eight months of liraglutide use in patients with T2DM and NAFLD significantly reduced carotid IMT, a surrogate marker of atherosclerosis, independently of glucometabolic changes.

Prevalence of atherosclerosis in patients with inactive rheumatoid arthritis

Patients with rheumatoid arthritis (RA) exhibit higher cardiovascular morbidity and mortality than the general population. The common carotid artery intima-media thickness (CCA-IMT) measured by ultrasound is a validated surrogate marker of atherosclerosis. We studied the prevalence of subclinical atherosclerosis in patients with inactive RA. CCA-IMT was measured at the level of the carotid bifurcation in 35 patients with RA and 35 age- and sex-matched controls. CCA-IMT measurements more than two standard deviations above the mean measurement of the control group were defined as abnormal. Patients and controls with known cardiovascular risk factors were excluded from the study. The following data were taken into consideration for each patient: age, sex, duration of RA, and medication received by the patient. These variables were adjusted in data analysis. The patients were required to have had normal C-reactive protein levels for at least 1 year and no clinical signs or symptoms of active disease. An independent t test and chi-squared test were used for statistical analysis. Nine patients with RA (25.7 %) and two controls (5.7 %) had an abnormal IMT. Patients showed more carotid atherosclerotic plaques and a higher mean CCA-IMT than did controls (48.6 vs. 14.3 % and 0.705 ± 0.140 vs. 0.580 ± 0.125, respectively). An abnormal CCA-IMT was more prevalent in patients >50 years of age with >5 years of involvement (P = 0.001). These results support the theory that chronic inflammation in patients with inactive RA is associated with atherosclerosis and suggest the use of carotid ultrasonography as a useful tool with which to establish the risk of cardiovascular disease.

Pitavastatin calcium improves endothelial function and delays the progress of atherosclerosis in patients with hypercholesterolemia.

Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia (HC) is unknown. To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation (FMD), carotid intima-media thickness (IMT), and arterial stiffness (β), three surrogate markers of atherosclerosis were studied in HC patients. A randomized, double-blind trial was performed with 40 HC subjects who fulfilled the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d (Group 1) or 2 mg/d (Group 2) for 8 weeks. There were 20 patients in each group, and 30 gender- and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated by β were measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on all subjects. At baseline, higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), reduced FMD, and increased β and IMT were observed in HC patients (P<0.001 for all) compared with controls. After 8 weeks, TC was decreased by 20.59%/27.56% and LDL-C 30.92%/35.64%, respectively, in comparison to baseline groups; the HC groups had reduced β and improved endothelial function over the 8-week follow-up (P<0.05-0.001); nonetheless, no significant alterations of IMT were found (P>0.05). Significant negative interactions between TC/LDL and FMD (P<0.05-0.001), positive interactions between TC and IMT (P=0.003) and between TC/LDL and β (P<0.001-0.000) were found. Treatment with pitavastatin calcium exerted favorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.

Interleukin-6 and asymmetric dimethylarginine are associated with platelet activation after percutaneous angioplasty with stent implantation.

Data linking in vivo platelet activation with inflammation and cardiovascular risk factors are scarce. Moreover, the interrelation between endothelial dysfunction as early marker of atherosclerosis and platelet activation has not been studied, so far. We therefore sought to investigate the associations of inflammation, endothelial dysfunction and cardiovascular risk factors with platelet activation and monocyte-platelet aggregate (MPA) formation in 330 patients undergoing angioplasty with stent implantation for atherosclerotic cardiovascular disease. P-selectin expression, activation of glycoprotein IIb/IIIa and MPA formation were determined by flow cytometry. Interleukin (IL)-6, high sensitivity C-reactive protein and asymmetric dimethylarginine (ADMA) were measured by commercially available assays. IL-6 was the only parameter which was independently associated with platelet P-selectin expression and activated GPIIb/IIIa as well as with leukocyte-platelet interaction in multivariate regression analysis (all p<0.05). ADMA was independently associated with GPIIb/IIIa activation (p<0.05). Patients with high IL-6 exhibited a significantly higher expression of P-selectin than patients with low IL-6 (p=0.001), whereas patients with high ADMA levels showed a more pronounced activation of GPIIb/IIIa than patients with low ADMA (p=0.003). In conclusion, IL-6 and ADMA are associated with platelet activation after percutaneous angioplasty with stent implantation. It remains to be established whether they act prothrombotic and atherogenic themselves or are just surrogate markers for atherosclerosis with concomitant platelet activation.

Age and sex differences in the effect of parental stroke on the progression of carotid intima-media thickness

Background and purposeParental stroke is a risk factor for stroke among the offspring. Carotid artery intima-media thickness (IMT) is a widely regarded surrogate marker for atherosclerosis and a predictive marker for stroke. This study examines whether parental stroke is associated with IMT progression. MethodsThis longitudinal study had two measures of IMT that were taken upon enrollment of the 521 subjects and after an average follow-up of 4.1 years. The rate of IMT progression was tested for associations with parental stroke and cardiovascular risk factors using ANCOVA models. Age and sex were also tested as effect modifiers. The subjects were allocated into the young or old group using the age of 55 years. ResultsParental history of stroke was significantly associated with progression of common carotid artery (CCA) IMT compared with no parental stroke history (13.52 vs. 10.43 μm/year, adjusted p = 0.035). The parental effect on IMT progression of the bifurcation and internal carotid artery was dependent on age group. Young subjects had faster progression, whereas older subjects with parental stroke had slower progression. There was a three-way interaction among sex, age, and parental stroke in CCA IMT progression, such that young women with parental stroke had a 69.7% faster progression than young women without parental stroke (15.58 vs. 9.18 μm/year). However, this difference was not found in young men or old subjects with and without parental stroke. ConclusionsParental stroke is associated with carotid artery IMT progression and is more obvious in the young, especially among women. The results emphasize the clinical significance of parental stroke risk on atherosclerosis in young women.

Can Erectile Dysfunction in Young Patients Serve as a Surrogate Marker for Coronary Artery Disease?

Early diagnosis and expeditious management of coronary artery disease (CAD) has a rewarding survival benefit. To study whether erectile dysfunction (ED) serves as a surrogate marker for CAD in a young patient. Males (n=207) between ages 20-60 years with ED were evaluated prospectively for risk factors for CAD. Blood Glucose Levels (BGL) fasting and post meal), lipid profile (LP) and 12 lead electrocardiogram (ECG) was done in all of them. International Index of Erectile Function-5 (IEF-5) was used for the evaluation of ED. Those with abnormal parameters were assessed by cardiologists by echocardiography, stress test and if necessary coronary angiography (Non-Invasive or Invasive). All the data were analysed using SPSS. 16 statistical software (SPSS Inc., Chicago, IL, USA). All data are expressed as mean and standard deviation. The Student's t-test was used to compare means between groups, and the chi-square test was used to compare proportions between the groups. P-value <0.05 was considered statistically significant. All confidence intervals (CIs) are two tailed and calculated at the 0.05 level. Out of 207, 149 patients had at least one abnormal screening parameter. All underwent cardiology consultation and 2D ECHO and Stress test. Thirty six patients underwent coronary angiography. CAD was found in 22 patients. Of these, 19 patients had severe ED. Nine patients were between 20-40 years of age (13.23%). All 9 young patients had deranged LP; severe ED. Six patients were smokers while nobody was hypertensive. ED serves as a surrogate marker for CAD in young patients (p=0.001). Presence of risk factors and lab abnormalities in young patients with ED warrants a cardiology referral to detect CAD.

Cocaine Use and Subclinical Coronary Artery Disease in Caucasians

Objective: Cocaine remains among the most commonly used and trafficked illicit drug in the world, and its use increases myocardial demand from elevated heart rate and blood pressure, and causes coronary vasospasm leading to myocardial infarction (MI). Surrogate markers for atherosclerosis of sub-clinical coronary artery disease (CAD) are often used to assess the presence of atherosclerosis in high-risk patients. Carotid intima media thickness (CIMT) as a surrogate marker for atherosclerosis is an independent predictor of future cardiovascular (CV) events and is routinely used in clinical studies. The objective of this preliminary study is to provide the baseline information on the presence of subclinical CAD in Caucasians with chronic cocaine use disorder using CIMT as a surrogate marker. Method: The study inclusion criteria included: a) Caucasian adult, 18 yrs and older with cocaine use disorder, as defined in Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5); and b) able to understand and sign the consent form (provided in English only). 40 participants were selected using convenient sampling, approached, and screened. Result: The mean LDL (low density lipoprotein), HDL (high density lipoprotein), and total cholesterol of the participants were within normal ranges. The mean right CIMT was 0.57 mm (± 0.01) and left CIMT was 0.59 mm (± 0.1). CIMT was found to be associated with route administration (p=0.0036) and smoking route had a significant positive association with the CIMT. Discussion: This study’s preliminary findings of no association between chronic cocaine use and sub-clinical CAD measured by CIMT in asymptomatic, young-to-middle-aged adult Caucasian cocaine users are new and in order to support these findings, larger prospective studies are warranted.

Canadian Multiethnicity—Differences in Coronary Artery Disease Prevalence and Progression and Relevance to Cardiac Imaging

The ethnic diversity of Canada is attributed to a steady rise in immigration, particularly from Asia. The diverse population demographics encompass a variety of cultural, linguistic, genetic, socioeconomic status, and clinical factors. The prevalence of coronary artery disease (CAD) varies among ethnic subgroups, being higher in South Asians than in Europeans and Chinese. These differences may be due to interactions among genetic and environmental factors and other factors that are still poorly understood. The predisposition and prevalence of underlying risk factors, such as hypertension, diabetes, obesity, smoking, and hyperlipidemia, also vary considerably among the different ethnic groups. An appreciation of these differences in assessing the risk of CAD is an important component of decision-making processes involving diagnosis and risk stratification of CAD in minority populations. In addition, the assessment of subclinical atherosclerosis using coronary calcium score or carotid intima media thickness as surrogate markers for atherosclerosis may allow for early and aggressive risk modification before the development of symptomatic CAD. Measures aimed at modifying these risk factors might reduce the prevalence of CAD in high-risk populations. The extent and progression of CAD may vary in these populations, resulting in perceptible differences in patient outcomes following myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. Ethnicity may also impact reference values of cardiac structure such as left ventricular parameters measured using echocardiography and cardiac magnetic resonance imaging. By understanding these differences, we may be able to improve health care strategies for ethnicity specific care, at primary and secondary prevention levels.

N-terminal fragment of probrain natriuretic peptide is associated with diabetes microvascular complications in type 2 diabetes.

Aim/introductionCirculating levels of N-terminal fragment of probrain natriuretic peptide (NT-proBNP) are established as a risk factor for cardiovascular disease and mortality in patients with diabetes, as well as in the general population. We sought to examine the possibility of NT-proBNP as a biomarker of microvascular complications in patients with type 2 diabetes.Materials and methodsIn total, 277 outpatients with type 2 diabetes were consecutively enrolled as a hospital cohort. Two hundred and seventeen of these patients (132 males; mean age, 63.4 years) were designated as cases with any of the diabetic complications (retinopathy, neuropathy, nephropathy, ischemic heart disease, strokes, peripheral artery disease), and 60 (42 males; mean age, 54.1 years) were set as controls without clinical evidence of diabetic complications. Diabetic complications were evaluated by medical record and routine laboratory examinations. NT-proBNP was measured and investigated with regard to the associations with diabetic complications.ResultsMean NT-proBNP levels were significantly higher in patients with any of the diabetic complications (59 versus 33 pg/mL; P<0.0001). In logistic regression analysis, NT-proBNP levels >79 pg/mL, which was the highest tertile, were independently associated with a 5.04 fold increased risk of all complications (P<0.0051) compared to the lowest tertile (NT-proBNP levels <31 pg/mL). Odd ratios of cardiovascular disease and nephropathy, neuropathy, and retinopathy were 9.33, 6.23, 6.6 and 13.78 respectively, in patients with NT-proBNP values in the highest tertile (>79 pg/mL), independently of age, sex, duration of diabetes or other risk factors, such as body mass index or hemoglobin A1c. In addition, NT-proBNP levels were associated with surrogate markers of atherosclerosis, such as brachial-ankle pulse wave velocity (r=0.449, P<0.0001) and left ventricular hypertrophy (r=0.212, P<0.001).ConclusionIn this hospital-based cohort of type 2 diabetes, the NT-proBNP levels were associated with systemic atherosclerosis and comorbid diabetic microvascular as well as macrovascular complications. It is useful to stratify high-risk diabetic patients by measuring NT-proBNP and to start comprehensive care for preventing the progression of diabetic complications. It is necessary to elucidate the underlying mechanism for the progression of diabetic complications represented by an elevation of NT-proBNP and to demonstrate the ability of NT-proBNP as a predictive global biomarker for diabetic complications in Japanese type 2 diabetic patients.

Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis.

BackgroundGalectin‐3 (Gal‐3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal‐3 in cardiovascular (CV) diseases. The role of Gal‐3 as a circulating biomarker has been demonstrated in patients with heart failure, but its importance as a biomarker in atherothrombosis is still unknown.Methods and ResultsBecause Gal‐3 is involved in monocyte‐to‐macrophage transition, we used fresh isolated monocytes and the in vitro model of macrophage differentiation of THP‐1 cells stimulated with phorbol myristate acetate (PMA). Gal‐3 release is increased by PMA in human monocytes and macrophages, a process involving exosomes and regulated by reactive oxygen species/NADPH oxidase activity. In asymptomatic subjects (n=199), Gal‐3 plasma levels are correlated with NADPH oxidase activity in peripheral blood mononuclear cells (r=0.476; P<0.001) and carotid intima‐media thickness (r=0.438; P<0.001), a surrogate marker of atherosclerosis. Accordingly, Gal‐3 plasma concentrations are increased in patients with carotid atherosclerosis (n=158), compared to control subjects (n=115; 14.3 [10.7 to 16.9] vs. 10.4 [8.6 to 12.5] ng/mL; P<0.001). Finally, on a 5‐year follow‐up study in patients with peripheral artery disease, Gal‐3 concentrations are significantly and independently associated with an increased risk for CV mortality (hazard ratio=2.24, 95% confidence interval: 1.06 to 4.73, P<0.05).ConclusionsGal‐3 extracellular levels could reflect key underlying mechanisms involved in atherosclerosis etiology, development, and plaque rupture, such as inflammation, infiltration of circulating cells and oxidative stress. Moreover, circulating Gal‐3 concentrations are associated with clinical outcomes in patients with atherothrombosis.

Carotid intima media thickness is associated with body fat abnormalities in HIV-infected patients.

BackgroundHIV-infected patients may be at increased risk of cardiovascular (CV) events, and lipodystrophy is generally associated with proatherogenic metabolic disturbances. Carotid intima-media thickness (cIMT) has been used as a surrogate marker for atherosclerosis and it has been shown to be an independent risk factor for CV disease. Our objective was to evaluate cIMT in HIV-infected patients on combined anti-retroviral therapy (cART) with and without lipodystrophy defined by fat mass ratio (L-FMR), and to determine the association of lipodystrophy and visceral obesity [(visceral (VAT), subcutaneous adipose tissue (SAT) volume and VAT/SAT ratio, objectively evaluated by CT scan] with cIMT.MethodsCross-sectional study of 199 HIV-infected patients. Body composition by DXA and abdominal CT, lipids, blood pressure, inflammatory markers, and cIMT by ultrasonography were performed. L-FMR was defined as the ratio of the percentage of trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical variables were compared using the chi-square or Fisher’s exact test. Spearman correlation coefficients were estimated to study the association between cIMT and clinical and metabolic characteristics. Means of cIMT, adjusted for age, were calculated, using generalized linear models.ResultsL-FMR was present in 41.2% of patients and cIMT was higher in these patients [0.81 (0.24) vs. 0.76 (0.25); p = 0.037)]. Lipodystrophic patients had higher VAT and VAT/SAT ratio and lower SAT. cIMT was associated with lipodystrophy evaluated by FMR, trunk fat, total abdominal fat, VAT and VAT/SAT ratio. No association was observed between cIMT and leg fat mass. Using generalized linear models, cIMT means were adjusted for age and no significant differences remained after this adjustment. The adjusted mean of cIMT was 0.787 (95% CI: 0.751-0.823) in patients without lipodystrophy, and 0.775 (95% CI: 0.732-0.817) in those with lipodystrophy (p = 0.671).ConclusionsHIV-infected patients on cART with lipodystrophy defined by FMR, had a significantly higher cIMT. Carotid IMT was also associated with classical cardiovascular risk factors. In these patients, visceral adipose tissue had a significant impact on cIMT, although age was the strongest associated factor.

Common Carotid Intima Media Thickness and Ankle-Brachial Pressure Index Correlate with Local but Not Global Atheroma Burden: A Cross Sectional Study Using Whole Body Magnetic Resonance Angiography

BackgroundCommon carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA).Methods50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50–70%, 3 = 70–99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated.ResultsThe atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β −0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β −0.45 p = 0.005).ConclusionABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden.

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases – Relationships and comparisons with vascular markers of atherosclerosis

BackgroundVisit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. MethodsWe prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18±9 outpatient clinic visits. ResultsAfter a mean 81±12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69±0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65±0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). ConclusionsCompared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases.

Increased arterial stiffness in systemic lupus erythematosus (SLE) patients at low risk for cardiovascular disease: a cross-sectional controlled study.

Cardiovascular disease (CVD) is a major cause of death in systemic lupus erythematosus (SLE) patients. Although the risk for cardiovascular events in patients with SLE is significant, the absolute number of events per year in any given cohort remains small. Thus, CVD risks stratification in patients with SLE focuses on surrogate markers for atherosclerosis at an early stage, such as reduced elasticity of arteries. Our study was designed to determine whether arterial stiffness is increased in SLE patients at low risk for CVD and analyze the role for traditional and non-traditional CVD risk factors on arterial stiffness in SLE. Carotid-femoral pulse wave velocity (PWV) was prospectively assessed as a measure of arterial stiffness in 41 SLE patients and 35 controls (CTL). Adjustment on age or Framingham score was performed using a logistic regression model. Factors associated with PWV were identified separately in SLE patients and in controls using Pearson's correlation coefficient for univariate analysis and multiple linear regression for multivariate analysis. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (1.8±3.6% in SLE vs 1.6±2.8% in CTL, p = 0.46). Pulse wave velocity was, however, higher in SLE patients (7.1±1.6 m/s) as compared to controls (6.3±0.8 m/s; p = 0.01, after Framingham score adjustment) and correlated with internal carotid wall thickness (p = 0.0017). In multivariable analysis, only systolic blood pressure (p = 0.0005) and cumulative dose of glucocorticoids (p = 0.01) were associated with PWV in SLE patients. Interestingly, the link between systolic blood pressure (SBP) and arterial stiffness was also confirmed in SLE patients with normal systolic blood pressure. In conclusion, arterial stiffness is increased in SLE patients despite a low risk for CVD according to Framingham score and is associated with systolic blood pressure and glucocorticoid therapy.

The milk-derived peptides Val-Pro-Pro and Ile-Pro-Pro attenuate arterial dysfunction in L-NAME-treated rats

Both endothelial dysfunction and arterial stiffness are surrogate markers of atherosclerosis and thus cardiovascular (CV) events. The milk-derived peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) inhibit angiotensin-converting enzyme, dilate blood vessels ex vivo and stimulate nitric oxide (NO) production in cells. In this study, we investigated the effects of either VPP or IPP on arterial function and on target organ damage in vivo. Male Wistar rats were treated with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 g l(-1)), L-NAME+VPP (0.3 g l(-1)) or L-NAME+IPP (0.3 g l(-1)) in their drinking water for 8 weeks. Plasma nitrite and nitrate (NOx) levels were significantly increased in normal Wistar rats after supplementation with either VPP or IPP but not in rats that were chronically treated with L-NAME. Acetylcholine-induced vasorelaxation in the thoracic aorta ring was impaired by L-NAME, whereas vasorelaxation was significantly greater in mice treated with L-NAME+VPP for 1 or 4 weeks or L-NAME+IPP for 4 weeks than in mice treated with L-NAME alone. Four weeks of treatment with either VPP or IPP attenuated the increase in pulse wave velocity (PWV) that was induced by L-NAME. Cardiac and renal damage were observed after 8 weeks of treatment with L-NAME, and either VPP or IPP attenuated this damage. These results show that VPP or IPP attenuates arterial dysfunction and suggest that milk-derived peptides might prevent CV damage.

Abstract P126: Influence of CIMT as a Motivator for Health Behavior Change in a Heart Health Program

Introduction: Carotid intima media thickness (CIMT) ultrasound is a known surrogate marker of atherosclerosis but few studies examine its influence on patient behavior. Motivation and self-efficacy (SE) are known predictors of health behavior change. This randomized, double-blind trial examined 1) use of CIMT images plus associated CVD risk to motivate adherence, and 2) the predictive ability of motivation and SE on adherence change. Methods: Patients with ≥ 2 cardiovascular disease (CVD) risk factors and subclinical atherosclerosis were assigned to either the intervention group [receive results weekly (R-CIMT)] or control group [withhold results (W-CIMT)]. All patients received a 12-week lifestyle program (Mediterranean diet, aerobic exercise, group support). Overall change in adherence from baseline to week 12 was determined using an ANCOVA model where % adherence was a composite measure of diet and exercise adherence. Initial motivation plus exercise and nutrition SE were assessed to determine their predictive ability of adherence in a standard regression model. Results: 166 patients randomized; 161 (R-CIMT n=81; W-CIMT n=80) eligible for intention-to-treat analysis. Patients were middle age (mean age = 54 ± 11 yrs), 62% (100 or 161) women, 48% (77 of 161) black. Baseline group differences: W-CIMT group was younger (52 vs 55 yrs; p=0.05), had a lower systolic blood pressure (120 vs 125; p=0.01), lower % family history of CVD (49 vs 65; p=0.03). In comparing R-CIMT vs W-CIMT groups, no difference was detected in overall % adherence change (16.4 ± 25.6 vs 19.8 ± 25.4; p=0.39). Initial motivation and SE measures were not predictive of change in adherence when added to group assignment (see Table). Conclusions: CIMT evidence of subclinical atherosclerosis increased participant CVD risk awareness but did not translate into actionable healthy behavior changes beyond those in the control group. Neither exercise nor dietary adherence was affected by initial motivation or self-efficacy when added to CIMT risk awareness.

Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism

β3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. Habitual exercise brings higher cardiorespiratory fitness and results in the amelioration of atherosclerotic risk factors. However, the effects of cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of cardiovascular disease remain unclear. A cross-sectional investigation of 877 Japanese men and women (18-75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism and risk of cardiovascular disease. Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake (V̇O(2peak)) during incremental cycle ergometer exercise testing. Subjects were divided into groups with high (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the median value of V̇O(2peak) for sex and decade. Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and V̇O(2peak) were higher in High-Fit subjects than Low-Fit subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P < 0.0001); however, ADRB3 polymorphism had no effect in High-Fit subjects. Higher levels of cardiorespiratory fitness may attenuate the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.