Increased carotid intima–media thickness associated with high hs-CRP levels is a predictor of unstable coronary artery disease

Abstract

Increased values of carotid intima–media thickness (CIMT) and high-sensitivity C-reactive protein (hs-CRP) are predictors of acute coronary events. We analysed the link between CIMT and hs-CRP in cases with coronary artery disease (CAD). From 1 January to 30 June 2012, we evaluated 43 patients with acute coronary syndrome (group A), 50 patients with stable coronary artery disease (group B) and 50 healthy volunteers (group C). All were analysed for CIMT and hs-CRP levels. CIMT values were higher in groups A and B (0.94 ± 0.21 mm, 0.89 ± 0.19 mm, respectively) and lower in group C (0.64 ± 0.09 mm), and this was statistically significant (p < 0.0001). However the values of hs-CRP were higher in group A (1.87 ± 0.36 mg/l) and lower in groups B and C (1.07 ± 0.28 mg/l, 0.97 ± 0.45 mg/l, respectively) and this was also statistically significant (p < 0.0001).     

Carotid and popliteal artery intima–media thickness in patients with poor oral hygiene and the association with acute-phase reactants

Purpose

The aim of this study was to evaluate whether poor oral hygiene is associated with carotid and popliteal arterial intima–media thickness, which is one of the predictors of future progression of sub-clinical atherosclerosis, and high-sensitivity C-reactive protein (hsCRP) and fibrinogen levels.

Methods

A specialised dentist checked the patients and selected 550 patients during periodontal examinations, according to their oral hygiene. The patients had no history of atherosclerotic disease. Carotid and popliteal artery B-mode ultrasonographic examinations and hsCRP and fibrinogen levels were analysed at baseline and after a mean of 6.2 months. The patients were scored on the DMFT index for the number of decayed (D), missing (M), and filled (F) teeth (T). We also used the Silness-Loe plaque index (SLI) to evaluate oral hygiene and dental plaque. The patients were divided into two groups using the DMFT and SLI criteria. Group I had a DMFT index score from 0 to 3 and SLI index score of 0 or 1. Group II had a DMFT index score from 4 to 28 and SLI index score of 2 or 3.

Results

A significant association was observed between dental status, oral hygiene, carotid and popliteal artery intima–media thickness and hsCRP level. Patients with increasing DMFT and SLI scores correlated with increasing carotid artery intima–media thickness.

Conclusions

The results clearly showed that chronic poor oral hygiene and tooth loss are related to sub-clinical atherosclerotic changes in the carotid arteries and may be indicative of future progression of atherosclerosis.     

Impaired coronary microvascular function and increased intima–media thickness in preeclampsia

There is an association between preeclampsia (PE) and excessive morbidity and mortality. Some recent studies have revealed the presence of endothelial dysfunction in PE patients with inflammatory activity. Moreover, it has been argued that the chronic inflammatory state involved in PE leads to an acceleration in atherosclerosis. Accordingly, our goal in this study is to determine whether there is any coronary microvascular dysfunction and increase in the intima–media thickness in patients who had mild PE 5 years before, without the presence of any traditional cardiovascular risk factors. The study included 33 mild PE patients (mild preeclampsia is classified as a blood pressure (BP) of 140/90 mm Hg or higher with proteinuria of 0.3 to 3 g/d) whose mean age was 33.7 years old, and 29 healthy women volunteers whose mean age was 36.1 years old. Each subject was examined using transthoracic echocardiography 5 years after their deliveries. During the echocardiographic examination, coronary flow reserve (CFR) and carotid intima–media thickness (IMT) were measured. There was a statistically lower CFR value in PE patients as compared with controls (2.39 ± 0.48 vs. 2.90 ± 0.49; P < .001). On the other hand, there was a significant increase in their IMT and high–sensitivity C–reactive protein (hs–CRP) values (respectively, 0.59 ± 0.15 vs. 0.46 ± 0.10; P < .001 and 3.80 ± 2.10 vs. 2.33 ± 1.79; P = .004). There was a negative correlation between the CFR values of the PE patients and hs-CRP (r = −0.568; P = .001) and IMT (r = −0.683, P < .001) results.We determined in the study that there was impaired CFR and increased carotid IMT in patients with PE, and, moreover, that these adverse effects were significantly correlated with hs-CRP.     

Carotid artery intima–media thickness,heat shock proteins and oxidized LDL autoantibodies in systemic necrotizing vasculitis

In this study we evaluate early atherosclerotic changes and determine whether anti-HSP-60, anti-HSP-65 and anti-oxLDL autoantibodies are elevated in systemic necrotizing vasculitis. Thirty-two patients having systemic necrotizing vasculitis were compared with normal controls and patients with systemic lupus erythematosus (SLE). The antibodies against human HSP-60, HSP-65 and oxLDL were measured by antihuman ELISA kit. All patients underwent non-invasive measurements of carotid artery intima-media thickness (IMT). In a comparison between carotid IMT extent between vasculitis patients and SLE, no significant differences were noted. Levels of anti-HSP-60, anti-HSP-65 IgG and anti-oxLDL autoantibodies were similar among patients compared to controls. IgM anti-HSP-60 antibody levels were significantly lower in patients compared to controls and a similar trend was found regarding IgM anti-HSP-65. As a group, patients having various necrotizing vasculitis have similar extent of early atherosclerotic changes regardless of the vasculitis type, and these levels are similar to those found in SLE.     

The association between increased carotid intima–media thickness and SYNTAX Score in coronary artery disease: A single center study

BackgroundCarotid artery lesions frequently coexist with coronary arterial disease (CAD). The aim of this study was to investigate the relation between carotid intima-media thickness (CIMT) and the extent of CAD and whether CIMT could be predictive of severity of coronary atherosclerosis.MethodsCoronary angiography and carotid ultrasound evaluations of 100 consecutive patients with CAD who had undergone elective coronary angiography were reviewed. IMT was measured at both carotid arteries. CIMT and severity of CAD relationship based on SYNTAX score was assessed. The relation between CIMT and cardiovascular risk factors was determined.ResultsMean overall SYNTAX score was 15.76 + 4.82. Mean right CIMT was 0.86 ± 0.29 and mean left CIMT was 0.83 ± 0.24. There were no significant correlation between the SYNTAX score and CIMT (r: 10, P: 30). There was significant relationship between hypertension,diabetes and CIMT (P: 0.01).Conclusionwe found no relationship between CIMT and SYNTAX score in patients who underwent coronary angiography. Diabetes mellitus and hypertension are related to increased carotid intima-media thickness.     

Carotid intima–media thickness value distributions in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Objective

Carotid intima–media thickness (IMT) is a noninvasive measurement of early atherosclerosis. Most IMT studies have involved populations with low rates of racial blending. The aim of the present article is to describe IMT value distributions and analyze the influence of sex and race on IMT values in a large Brazilian sample, a setting with a high rate of racial admixture.

Methods

The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a multicenter cohort of 15,105 adult (aged 35–74 years) civil servants in six Brazilian cities. Baseline assessment included IMT measurements in both common carotid arteries. Race was self-reported. We studied the association between sex and race with IMT values using multiple linear regression models. We conducted analyses in all and low-risk individuals, defined as those without classical cardiovascular risk factors.

Results

We analyzed complete IMT data from 10,405 ELSA-Brasil participants. We present nomograms by age for all and low-risk individuals, stratified by sex and race. We found that men had significantly higher maximal IMT values compared with women (β = 0.058; P < 0.001). This association remained for low-risk individuals (β = 0.027; P = 0.001). In addition, Brown and White individuals had lower maximal IMT values compared with Black individuals for all (β = −0.034 and β = −0.054, respectively; P < 0.001) and low-risk individuals (β = −0.027; P = 0.013 and β = −0.035; P < 0.001, respectively).

Conclusion

We found significantly higher IMT values in men. We found significantly higher IMT values in Black individuals than White and Brown individuals. These results persisted when analyses were restricted to low-risk individuals.     

Impaired systolic blood dipping and nocturnal hypertension: an independent predictor of carotid intima–media thickness in type 1 diabetic patients

ObjectiveType 1 diabetes in children predicts a broad range of later health problems including an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate whether nocturnal hypertension and impaired nocturnal dipping affect atherosclerosis in children and adolescents with type 1 diabetes and to investigate the relationship between atherogenic risk factors and carotid intima–media thickness (CIMT).MethodsOne hundred fifty-nine type 1 diabetic patients and 100 healthy controls were included in the study. We investigated metabolic and anthropometric parameters such as body mass index (BMI), waist circumference, fasting glucose and insulin, serum lipids, 24 h ambulatory blood pressure monitoring (ABPM), and CIMT and compared these with those in control subjects (CS).ResultsNo difference was found between type 1 diabetic patients and CS in age, weight, waist/hip ratio, triglyceride, HDL-cholesterol level. However in children with type 1 diabetes, total cholesterol (p = 0.016),and LDL-cholesterol (p = 0.002) levels and CIMT (P < 0.001) were greater than those of controls. It was determined that 10% of type 1 diabetic patients had dyslipidemia.In 23.2% of type 1 diabetic patients, ABPM showed arterial hypertension. CIMT was significantly higher in the hypertensive group than in the nonhypertensive group (P = 0.003).Twenty-three (14.4%) diabetic patients had nocturnal hypertension. CIMT was significantly greater in the nocturnal hypertensive group (p = 0.023).Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) dipping was significantly different in diabetic patients (P < 0.001).CIMT was correlated positively with Hba1c (r = 0.220, p = 0.037), and negatively with SBP dipping (r = − 0.362, p = 0.020) in the diabetic patients.In stepwise regression analysis, Hba1c and SBP dipping emerged as a significant predictor of CIMT (β = 0.300, p = 0.044, β = 0.398 p = 0.009) contributing to 15.58% of its variability.ConclusionThese results provide additional evidence for the presence of subclinical cardiovascular disease (CVD) and its relation to hypertension in type 1 diabetic patients. They also indicate a significant relation between nocturnal hypertension, SBP dipping and increased arterial stiffness. It is also important to note that our findings reveal significant relationships between HBA1c cardiovascular changes and underline the importance of glucose control to predict CVD.     

Increased augmentation of central blood pressure is associated with increases in carotid intima–media thickness in type 2 diabetic patients

Aims/hypothesis Type 2 diabetes is associated with a two- to seven-fold increase in cardiovascular morbidity and mortality. The aim of this study was to determine the relationships between intima–media thickness (IMT), an established marker of atherosclerosis, large artery function and other determinants of cardiovascular risk in type 2 diabetic patients.Methods We studied 228 type 2 diabetic patients (75 women, aged 62±2 years [mean±SEM]). Carotid IMT was bilaterally measured using ultrasound technology. Applanation tonometry and pulse wave analysis were used to measure aortic systolic and diastolic blood pressures, central pressure augmentation (AG) and the augmentation index (AIx), a measure of systemic arterial stiffness. Conventional cardiovascular risk factors (lipids, HbA₁c, smoking and diabetes duration) were also assessed.Results Women had higher AG and AIx (p<0.0001), despite comparable systolic BP and heart rate in women and men. In women, AG (r=0.39, p<0.001), age (r=0.32, p<0.01), brachial systolic BP (r=0.34, p<0.01) and aortic systolic BP (r=0.34, p<0.01) correlated with IMT. In men, age (r=0.41, p<0.001), diabetes duration (r=0.25, p<0.01), AG (r=0.22, p<0.01), aortic systolic BP (r=0.21, p<0.01), brachial systolic BP (r=0.21, p<0.01) and body weight (r=0.16, p<0.05) correlated with IMT. In multiple linear regression analyses, AG and aortic systolic BP, but not brachial systolic BP, were age-independent determinants of IMT in men and women. In all patients, increased AG (adjusted for sex, age and heart rate) correlated with longer duration of diabetes, urinary albumin excretion and IMT.Conclusions/interpretation Measures of central systolic pressure correlate with carotid IMT, independently of age and other risk markers.     

Carotid artery intima-media thickness in patients with autoimmune connective tissue diseases: a case–control study

Patients with autoimmune rheumatic disorders have an increased incidence of cardiovascular (CV) events and mortality. Despite this being related to a high prevalence of the traditional CV risk factors, systemic inflammation has been postulated to be an independent CV risk factor, particularly in patients with rheumatoid arthritis (RA). However, data are still controversial. We designed a case–control study, in which patients with autoimmune rheumatic disorders were matched with age-, sex-matched controls. Prevalence of early atherosclerosis was assessed by carotid artery intima-media thickness (IMT) measurement. IMT values were considered normal (IMT ≤ 0.9 mm) or abnormal (IMT > 0.9). Multivariate analysis was performed to identify predictors of pathological IMT. Overall, 152 patients and 140 matched controls were enrolled. Prevalence of >0.9 mm IMT values did not significantly differ between patients with autoimmune rheumatic disorders and controls (61 vs. 69%, p = 0.1). In detail, a similar IMT distribution between the 69 RA patients and controls was observed. Cases with a CV risk factor showed a higher prevalence of pathological IMT as compared to those without any risk factor, both in patients (77.1 vs. 38.6%; p < 0.0001) and controls (84.6 vs. 25%; p < 0.0001). At multivariate analysis, age and presence of CV risk factors were found to be independent predictors of >0.9 mm IMT, while RA as well as any other considered rheumatic disease were not. Our data found a similar prevalence of preclinical arterial wall atherosclerotic damage in patients with autoimmune rheumatic diseases and matched controls. Presence of traditional CV risk factors and patient age remain the main factors involved in preclinical atherosclerosis in patients with autoimmune rheumatic disorders, including RA.     

Association between levels of serum perfluorooctane sulfate and carotid artery intima–media thickness in adolescents and young adults

Background

Perfluorinated chemicals (PFCs) have been widely used for years in a variety of products worldwide. Although epidemiological findings have shown that PFC levels are positively associated with cholesterol and uric acid levels, it is unknown whether PFCs are associated with atherosclerosis.

Methods

We recruited 664 subjects (12–30 years) from a population-based sample of adolescents and young adults based on a mass urine screening to determine the relationship between serum levels of PFCs and carotid intima–media thickness (CIMT).

Results

The median concentrations and ranges of perfluorooctanoic acid (PFOA), perfluorooctane sulfate (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFUA) were 3.49 (0.75–52.2) ng/mL, 8.65 (0.11–85.90) ng/mL, 0.38 (0.38–25.4) ng/mL, and 6.59 (1.50–105.7) ng/mL, respectively. After controlling for age, gender, smoking status, systolic blood pressure, body mass index, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance, multiple linear regression analysis revealed that CIMT increased significantly across quartiles of PFOS (0.434 mm, 0.446 mm, 0.458 mm, 0.451 mm; P for trend < 0.001). Subpopulation analysis showed the association between PFOS and CIMT was more evident and significant in females, non-smokers, subjects of age 12–19 years, BMI < 24, and those with APOE genotype of E2 carrier and E3/E3.

Conclusions

Higher serum concentrations of PFOS were associated with an increase of carotid IMT in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between PFOS and atherosclerosis.     

Reduced carotid intima–media thickness in systemic lupus erythematosus patients treated with cyclosporine A

Abstract

Background Patients with systemic lupus erythematosus (SLE) are at risk of atherosclerosis. An increased carotid intima–media thickness (IMT) is considered to be a marker of early atherosclerosis.

Objective To determine influential factors for increased carotid IMT in SLE patients.

Methods We evaluated the impact of conventional risk factors for atherosclerosis on carotid IMT in 427 healthy controls and of clinical factors on carotid IMT in 94 SLE patients. Carotid IMT was measured by using a newly developed computer-automated system. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CI).

Results Multivariate-adjusted mean carotid IMT (mm) was significantly reduced in SLE patients (0.51, 95 % CI = 0.36–0.66) compared to healthy controls (0.55, 95 % CI = 0.40–0.70) (P = 0.003). The SLE Disease Activity Index (SLEDAI) was associated with carotid IMT in a dose-dependent manner (P_trend = 0.041). The current use of cyclosporine A (adjusted OR = 0.02, 95 % CI = 0.01–0.40, P = 0.011) and a history of steroid pulse therapy (adjusted OR = 0.01, 95 % CI = 0.01–0.25, P = 0.006) were significantly associated with a decreased risk of increased carotid IMT.

Conclusions Our findings suggest that the current use of cyclosporine A can protect against increased carotid IMT, leading to a decreased risk of arteriosclerosis. Future studies with a larger sample size need to confirm that this association holds longitudinally.     

A comparative study of arterial stiffness, flow-mediated vasodilation of the brachial artery, and the thickness of the carotid artery intima–media in patients with systemic autoimmune diseases

Patients with autoimmune diseases may have increased vascular risk leading to higher mortality rates. Novel imaging techniques are necessary for the early assessment and management of these patients. In this study, we compared augmentation index (AIx) and pulse wave velocity (PWV), indicators of arterial stiffness, to brachial arterial flow-mediated vasodilation (FMD) and common carotid artery intima–media thickness (ccIMT), standard indicators of endothelial dysfunction and atherosclerosis, respectively. We wished to assess the vascular status of autoimmune patients by using a novel, cheap, and reproducible technique, the arteriograph. Altogether, 101 patients with systemic autoimmune diseases including primary antiphospholipid syndrome, systemic sclerosis, rheumatoid arthritis, and polymyositis, all having various types of vasculopathies, as well as 36 healthy individuals were investigated. Arterial stiffness was assessed by a TensioClinic arteriograph, a recently validated technique. Brachial arterial FMD and ccIMT were determined using high-resolution ultrasonography. Autoimmune patients exerted impaired FMD (3.7 ± 3.8%), increased ccIMT (0.7 ± 0.2 mm), AIx (1.2 ± 32.2%), and PWV (9.7 ± 2.4 m/s) in comparison to control subjects (FMD = 8.4 ± 4.0%; ccIMT = 0.6 ± 0.1 mm; Aix = −41.1 ± 22.5%; PWV = 8.0 ± 1.5 m/s; p < 0.05). We found a significant negative correlation of FMD with AIx (R = −0.64; p < 0.0001) and PWV (R = −0.37; p = 0.00014). There were significant positive correlations between ccIMT and AIx (R = 0.34; p = 0.0009), ccIMT and PWV (R = 0.44; p < 0.0001), as well as AIx and PWV (R = 0.47; p < 0.0001). AIx, PWV, and ccIMT positively correlated and FMD negatively correlated with the age of the autoimmune patients. Arterial stiffness indicated by increased AIx and PWV may be strongly associated with endothelial dysfunction and overt atherosclerosis in patients with autoimmune diseases. Assessment of arterial stiffness, FMD, and ccIMT are reproducible and reliable noninvasive techniques for the complex assessment of vascular abnormalities in patients at high risk.     

Family histories of Type II diabetes and hypertension predict intima–media thickness in patients with Type I diabetes

AIMS/HYPOTHESIS: Hyperglycaemia predicts microvascular complications but data on macrovascular disease are limited. We searched for predictors of carotid artery intima-media thickness in young adults with Type I (insulin-dependent) diabetes mellitus. METHODS: A total of 71 children (F/M = 34/37) were followed after their diagnosis until they reached 32 +/- 1 years of age, when duration of diabetes averaged 22 +/- 1 years. Cardiovascular risk markers [lipids, blood pressure, smoking, urinary albumin excretion rate, lifetime glycaemic exposure (A(1c) months), exercise habits, alcohol consumption, family history] were evaluated at age 21 +/- 1 for the baseline examination and at age 32 +/- 1 years for the follow-up examination years. During follow-up, intima-media thickness of common and internal carotid arteries and the carotid bulb were quantitated using a high-resolution B-mode ultrasound. RESULTS: In univariate analysis, age, BMI, blood pressure, lifetime glycaemic exposure, a positive family history of Type II (non-insulin-dependent) diabetes mellitus, hypertension and cardiovascular disease were predictors of carotid intima-media thickness. In multivariate analysis, a positive family history of Type II diabetes predicted maximal ( p< 0.05) and common ( p< 0.005) carotid artery intima-media thickness, family history of hypertension predicted increases in maximal ( p< 0.04), and far wall ( p< 0.006) carotid artery intima-media thickness, and lifetime glycaemic exposure was an independent predictor of increased carotid bulb thickness ( p< 0.03). CONCLUSION/INTERPRETATION: Positive family histories of Type II diabetes and hypertension are independent predictors of carotid intima-media thickness in patients with Type I diabetes, and could therefore predispose these patients to atherosclerosis     

Revisiting the frequency of peripheral arterial disease in patients with coronary artery disease: is there a difference between diabetic and non-diabetic patients?

BACKGROUND: The aim of this study was to investigate whether frequency of concomitant peripheral arterial disease (PAD) is associated with angiographic severity of coronary artery disease (CAD), as well as to ascertain if diabetic patients differ from those without diabetes in the association between these two manifestations of atherosclerosis. PATIENTS AND METHODS: This study included 302 patients (229 men, mean age 62.2 +/- 11.5 years) with documented CAD, divided into groups I-III, according to the angiographic severity of coronary atherosclerosis. Group I comprised 140 patients (104 men) with severe CAD, group II comprised 63 patients (48 men) with moderate CAD and group III comprised 99 patients (77 men) with mild CAD. Each of the groups I-III was further divided into the subgroups of diabetic and non-diabetic patients. Included were also 88 patients (42 men, mean age 61.7 +/- 9.5 years) without CAD and a control group of 60 healthy volunteers (30 men), aged 18-40 years. PAD was diagnosed by means of a Doppler apparatus. RESULTS: Frequency of PAD was associated with angiographic severity of CAD (p = 0.0001). This association was shown both in diabetic (p = 0.012) and in non-diabetic patients (p = 0.0041). Significantly (p < or = 0.01) higher frequency of PAD among diabetic patients was found in each of the groups I-III. CONCLUSIONS: Among patients with CAD, frequency of concomitant PAD is associated with angiographic severity of coronary atherosclerosis. This association is demonstrated both in diabetic and in non-diabetic patients. Finally, PAD is significantly more frequent in diabetic patients, irrespective of the angiographic severity of CAD.