Coronary calcification is more predictive of carotid intimal medial thickness in black compared to white middle aged men

BackgroundRace-specific data for the association between coronary artery calcification (CAC) and carotid intimal medial thickness (IMT) are limited. We sought to compare black-white specific associations of these two measures.MethodsWe conducted a population-based study of 379 randomly selected men aged 40–49 years (84 black and 295 white) from Allegheny County, US (2004–2006). Agatston CAC score was evaluated by electron-beam tomography and carotid IMT was evaluated by ultrasonography.ResultsCompared to white men, black men had similar prevalence of CAC (p = 0.56) and higher total carotid IMT (p < 0.001). In black and white men, CAC score had significant positive correlations with total carotid IMT (r = 0.47 and r = 0.24, respectively, p < 0.001 for both) as well as the IMT for the common carotid artery (CCA), internal carotid artery and carotid bulb. The associations of CAC with total and CCA IMT were significantly stronger in black (β = 0.07 and β = 0.05, respectively) than white men (β = 0.03 and β = 0.01, respectively) after adjustment for traditional coronary risk factors (p = 0.046 and p = 0.036, respectively).ConclusionsIn black and white middle aged men, CAC score had significant positive correlations with total and segmental carotid IMT. CAC was more predictive of total and CCA IMT in black than white men independent of coronary risk factors.     

Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Vitamin C consumption is associated with less progression in carotid intima media thickness in elderly men: A 3-year intervention study

Background and aimPlant foods may lower the risk of cardiovascular disease.Methods and resultsWe assessed changes in the intima media thickness (IMT) of the carotid artery and diet in elderly men. Men (n = 563) aged 70 ± 5 years were randomly assigned to 1 of 4 groups (dietary intervention, omega-3 supplementation, both or neither) using a 2 × 2 factorial design. B-mode ultrasound of the carotid arteries and calculation of dietary intake were performed at baseline and after 3 years. We previously showed that omega-3 supplementation did not influence the IMT, thus the dietary intervention (n = 233) and no dietary intervention (n = 231) groups were pooled.The dietary intervention group had less progression in the carotid IMT compared with the controls (0.044 ± 0.091 mm versus 0.062 ± 0.105 mm; P = 0.047). This group increased their daily vitamin C intake (P = 0.005) and intake of fruit, berries and vegetables (P ≤ 0.001). Increased intake of vitamin C and of fruit and berries was inversely associated with IMT progression (r = −0.181; P = 0.006 and r = −0.125; P = 0.056, respectively). Multivariate linear regression analysis showed that increased intakes of vitamin C and of fruit and berries were associated with less IMT progression in the intervention group and in the total study population, after adjustment for consumption of dietary cholesterol, cheese, saturated fat and group assignment.ConclusionVitamin C containing foods may protect against the progression of carotid atherosclerosis in elderly men.     

Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease

Background and aimsApolipoprotein E (apoE) polymorphism plays a significant role in the development of atherosclerosis and cardiovascular disease. Therefore, the aim of the present study was to examine the association between apoE polymorphism and carotid intima-media thickness (IMT), and severity and extent of coronary artery disease (CAD).Methods and resultsB-mode ultrasound and quantitative coronary angiography (QCA) were used to assess carotid, and coronary artery atherosclerosis in 91 patients with clinically suspected CAD referred for cardiac catheterization. Two apoE phenotype groups were defined: apoE3 (E3/E3) and apoE4 (including E4/E3, E4/E4 phenotypes). Maximum IMT was higher in the apoE4 group than in the apoE3 group (p = 0.022). The global atheroma burden index was similarly higher in the apoE4 group than in the apoE3 group (p = 0.033). ApoE4 subjects had higher levels of apolipoprotein B (apoB) (p = 0.008), triglycerides (p = 0.006), remnant lipoprotein-cholesterol (RLP-C) (p = 0.023), and lipoprotein(a) [(Lp(a)] (p = 0.041) than apoE3 subjects. The mean LDL particle size was smaller in the apoE4 group than in the apoE3 group (p = 0.041).ConclusionsApoE polymorphism was associated with both carotid and coronary atherosclerosis. Patients with the apoE4 isoform had an increased carotid IMT and a more severe and extensive CAD than patients with the apoE3 isoform.     

Role of endogenous androgens on carotid atherosclerosis in non-obese postmenopausal women

BackgroundRecent randomized trials on hormone replacement therapy in postmenopausal women raised many doubts about their role in cardiovascular disease prevention. Therefore the role of other sex hormones needed to be investigated. In particular androgens seem to have a protective role on atherosclerosis. The present study was performed to assess the role of endogenous sex hormones on carotid atherosclerosis in postmenopausal women.Methods and resultsWe consecutively enrolled 101 postmenopausal women aged 45–75 (mean age 57.4) years referred to our University hospital menopausal health-screening clinic. The subjects underwent a medical history, a physical examination and biochemical analysis. Extracranial carotid arteries were assessed by ultrasound. Fifty percent of our sample had carotid plaques. On the multivariate logistic regression analysis age, glycaemia (positively) and testosterone (negatively) (P = 0.02) were significantly correlated to carotid atherosclerosis. In non-obese subjects we found that participants in the third tertile had a significantly lower prevalence of carotid atherosclerosis (P = 0.02) compared to those in the first tertile of testosterone.ConclusionsThese results suggest a possible protective role of endogenous androgens at least on carotid atherosclerosis. Of course these preliminary results should be supported by prospective studies. Also the different role of these hormones on obese and non-obese subjects needs to be clarified.     

Cardiovascular risk factors and subclinical atherosclerosis among Nunavik Inuit

ObjectiveTo evaluate subclinical atherosclerosis in Nunavik Inuit and its correlation to traditional cardiovascular disease risk factor.MethodThe intima–media thickness (IMT) of 12 segments of the carotid arteries (IMT_{12_seg}) free of plaque were assessed in randomly selected 40 years old and older Inuit from. Clinical assessment was performed which included fasting plasma glucose, fasting insulin, systemic blood pressure, body mass index, smoking, circulating blood lipids and oral glucose tolerance test. In addition, documented presence of ischemic heart disease (IHD), stroke, diabetes mellitus, hypertension and dyslipidemia were determined from medical files.ResultsThe average age of the 287 participants was 51.2 ± 0.6 years (56.8% women). Mean IMT_{12_seg} was 0.80 ± 0.17 mm (range: 0.55–1.47 mm). Compared with disease free Inuit, individuals with history of stroke showed greater carotid internal IMT (0.68 ± 0.01 mm vs. 0.96 ± 0.15 mm respectively; p < 0.005) but no difference was observed for IHD. Hypertensive and dyslipidemic Inuit had higher IMT_{12_seg} compared to risk factor free individuals but no difference was observed in diabetics. None of the clinical assessments were associated with IMT_{12_seg}. In a multivariate backward elimination model, only age, gender, and medically documented history of hypertension were found to be predictors of IMT_{12_seg} (adjusted r-square of 0.54; p < 0.0001).ConclusionCompared with disease free Nunavik Inuit, subclinical signs of atherosclerosis determined by IMT was higher in individual diagnosed with stroke. Independent predictors of IMT_{12_seg} in our group were age, gender and history of hypertension. No other traditional risk factors imparted IMT.     

Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis

ObjectiveThere is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors.DesignA case–control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls.MethodsWe assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT.ResultsThe common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08–8.38%], p < 0.0001) or 0.044 mm [0.021–0.066 mm] (p = 0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5–29.4%] or 0.250 mm [0.198–0.303 mm] higher in HIV patients (p < 0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART).ConclusionsHIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4–14% greater and the “vascular age” 4–5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.     

Intima-media thickness is a useful marker of the extent of coronary artery disease in patients with impaired renal function

ObjectiveThe aim of the study was the assessment of intima-media thickness (IMT) in peripheral arteries (the carotid and the femoral artery) and its correlation with the extent of coronary artery disease (CAD). The second task was the analysis of the renal function's influence within IMT complex.Methods231 patients (men, mean age 52.8), who had undergone coronary angiography due to symptoms of CAD were enrolled. The ultrasound measurement of IMT in the common carotid artery (CCA), carotid bulb and common femoral artery (CFA) was performed. The relationship between IMT, renal function and the extent of CAD was evaluated.ResultsSignificantly higher values of IMT in the peripheral arteries were observed in patients with CAD than in those without (CCA—0.91 vs 0.61 mm, carotid bulb—1.31 vs 0.67, CFA—1.38 vs 0.63 respectively, p < 0.0001). The GFR values in the CAD patients significantly negatively correlated with IMT complex in CCA (p < 0.001) and carotid bulb (p < 0.05). Lower values of GFR in patients with three-vessel disease were observed than in those patients with one- or two-vessel disease (p < 0.05). In multifactoral analysis (post-hoc NIR test) we found that glomerular filtration rate (GFR) is strongly determined by age (p < 0.0001), BMI (p < 0.0001), value of carotid intima-media thickness (p < 0.001), value of IMT in the carotid bulb (p < 0.02) and the treatment with ACE-I (p < 0.05). In multifactoral analysis we did not find any statistical influence of lipid profile and glucose disturbances on GFR.ConclusionsHigher peripheral artery IMTs in patients with CAD than in those without and patients with three-vessel disease indicate that IMT may be used as an early marker of atherosclerosis and reflect the severity of CAD. A significant negative correlation between the value of a GFR and the IMT confirmed the usefulness of this noninvasive method for the estimation of preclinical stages of atherosclerotic changes’ development in patients with impaired renal function.     

Brachial artery vasoreactivity is associated with cross-sectional and longitudinal anatomical measures of atherosclerosis in postmenopausal women with coronary artery disease

BackgroundThe diagnostic and prognostic importance of brachial artery flow-mediated dilation (BFMD) for cardiovascular disease (CVD) is not certain and associations between BFMD and recognized measures of atherosclerosis have not been well established.MethodsWe investigated cross-sectional and longitudinal correlations between repeated measures of BFMD and quantitative coronary artery angiographic (QCA) measurements of average percent diameter stenosis, number of lesions and minimum luminal diameter (MLD), and ultrasonographic measurement of carotid artery intima-media thickness (CIMT) in an ethnically diverse cohort of postmenopausal women (n = 132) with coronary artery disease (CAD). Subjects were participants in a 3-year randomized, placebo-controlled clinical trial, testing the efficacy of hormone therapy on atherosclerosis progression. Associations between BFMD and QCA measures, and between BFMD and CIMT were examined using measurements from the same study visit.ResultsBFMD was significantly inversely correlated with coronary artery stenosis at baseline (β = ?1.21% [S.E.(β) = 0.38], p = 0.002). BFMD levels significantly predicted rate of change in CIMT over the trial period (β = ?0.76 μm/year [S.E.(β) = 0.29], p = 0.008).ConclusionsPhysiological and anatomical measures of atherosclerosis are correlated among postmenopausal women with CAD, which provides some validation of BFMD as a measure of atherosclerosis in high-risk populations.     

Slow heart rate recovery after exercise is associated with carotid atherosclerosis

ObjectiveSlow heart rate recovery (HRR) after exercise is an estimate of impaired parasympathetic tone and predictor of all-cause and cardiovascular mortality. Carotid atherosclerosis is associated with high risk of developing coronary heart disease (CHD) and stroke. We tested the hypothesis that slow HRR is associated with carotid atherosclerosis in a cross-sectional study of 12,712 middle-aged men (age 49.1 ± 8.9 years).MethodsCarotid atherosclerosis was measured using B-mode ultrasonography and defined as stenosis >25% and/or intima–media thickness >1.2 mm. HRR was calculated as the difference between peak heart rate during a graded exercise treadmill test and heart rate 2 min after cessation of exercise.ResultsThe prevalence of carotid atherosclerosis was 8.4%. The prevalence of atherosclerosis was significantly higher among subjects in the lowest (<44 bpm) versus the highest (>61 bpm) quartile of HRR (14.4% versus 4.1%, p < 0.001). In multivariable logistic regression models adjusted for established CHD risk factors, inflammatory markers, and exercise capacity, subjects in the lowest quartile of HRR (<44 bpm) were 1.50 times (95% CI: 1.13–2.00) more likely to have carotid atherosclerosis than subjects in the highest quartile (HRR >61 bpm).ConclusionsSlow heart rate recovery after exercise, an index of decreased parasympathetic activity, is associated with carotid atherosclerosis independent of established risk factors in middle-age men.     

High-density lipoprotein-cholesterol and risk of stroke and carotid atherosclerosis: a systematic review

Background and purposeEpidemiological studies have found no relationship between total cholesterol and stroke risk, but little attention has been paid to high-density lipoprotein-cholesterol (HDL-C).MethodsWe performed a systematic PubMed literature search for epidemiological studies that examined the association between HDL-C level and stroke or carotid intima-media thickness (IMT).ResultsWe identified 18 studies on the relationship between HDL-C and stroke risk and 37 on HDL-C and carotid IMT. Eight of ten prospective cohort studies (n = 238 739) and three of eight case–control studies (n = 3604 cases, 8220 controls) supported an association between elevated HDL-C level and decreased risk of stroke. Prospective cohort studies reporting on relative risk per unit increase in HDL-C showed an 11–15% decreased stroke risk per 10-mg/dl increase in HDL-C. Of 37 studies on carotid IMT, 31 reported cross-sectional, one longitudinal, and five both cross-sectional and longitudinal associations between HDL-C level and carotid IMT. Of 36 cross-sectional studies (n = 51 288), 20 showed an inverse association between HDL-C level and carotid IMT. Of six longitudinal studies (n = 20 065), three showed no association, one showed a weak association in a subgroup of white women and two showed a significant inverse relationship between HDL-C level and carotid IMT. Pooled estimates could not be calculated because of the variation in study designs and analysis.ConclusionsThe weight of evidence in the literature supports an inverse association between HDL-C level and stroke or carotid atherosclerosis, but more data are needed to firmly establish this protective effect.     

Interaction between the uncoupling protein 2 -866G>A gene variant and cigarette smoking to increase oxidative stress in subjects with diabetes

Background and aimsIncreased oxidative stress is associated with coronary heart disease (CHD). The mitochondrial uncoupling protein-2 (UCP2) negatively regulates reactive oxygen species generation. We have observed that a common variant (−866G>A) in the promoter region of UCP2 is associated with increased CHD risk in healthy men and increased oxidative stress in diabetic men with CHD. The aim of the current study was to test the hypothesis that this variant might interact with smoking (an environmental stress) to influence plasma markers of oxidative stress.Methods and resultsAmongst 453 Caucasian diabetic men there was a significant interaction (p = 0.001) between genotype and smoking in determining plasma Total AntiOxidant Status (TAOS). Current smokers with the −866AA genotype had the lowest TAOS (indicating higher oxidative stress) of all subjects (AA vs. GG: 32.00 ± 17.4% vs. 45.8 ± 12.6%, p = 0.04). In a sub-sample of 20 subjects (10 GG, 10 AA) matched for baseline characteristics, plasma markers of oxidative stress in current smokers were significantly higher in AA compared to GG subjects (TAOS 36.8 ± 9.5% vs. 51.4 ± 9.5%, p = 0.04; F₂-isoprostanes 1133.6 ± 701.2 pg ml⁻¹vs. 500.8 ± 64.7 pg ml⁻¹, p = 0.04).ConclusionsThis study demonstrates an interaction between the UCP2 −866G>A variant and smoking to increase oxidative stress in vivo.     

Large brachial and common carotid artery diameter in postmenopausal women with carotid atherosclerosis

Background and purposeIt is recognized that arteries can enlarge to compensate atherosclerosis. The role of diameter enlargement of unaffected arteries is not well known. We hypothesized that brachial and common carotid arteries diameters were larger in subjects with carotid atherosclerosis compared to subjects without these lesions.MethodsWe measured diameters in the common carotid and brachial arteries. Intimal medial thickness (IMT) of carotid arteries and carotid atherosclerosis were also evaluated using ultrasound in 83 cases and 83 disease-free control subjects.ResultsCommon carotid and brachial diameter was greater in cases (subjects with carotid atherosclerosis) than controls (subjects without carotid atherosclerosis) after adjustment for confounding variables (P < 0.02). Common carotid diameter was also larger in individuals with greater IMT (P < 0.0001), whereas brachial artery diameter was not. Subjects with more than one carotid plaque had larger arterial diameters than those with one or without plaques.ConclusionsCommon carotid and brachial artery diameters are both larger in cases than controls. This result suggests that vascular remodeling is a systemic process and not only a local response to atherosclerosis. The relationship between diameters and burden of disease could also suggest a link between vascular remodeling and severity of disease. Finally, if confirmed in prospective studies, brachial artery diameter could help to identify subjects at high cardiovascular risk, at least in postmenopausal women.     

Retinal microvascular abnormalities are associated with early carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes mellitus

ObjectiveControversies concerning the association of retinal microvascular abnormalities (RMAs) with atherosclerosis in patients with diabetes exist. The objective of this study was to investigate the association between RMAs and carotid atherosclerotic lesions in Chinese inpatients with type 2 diabetes.MethodsThis cross-sectional study involved 2870 type 2 diabetic patients including 1602 men aged 15–90 years and 1268 women aged 17–88 years. Both retinal arteriosclerosis (RA) and diabetic retinopathy (DR) were determined by digital fundus photography using a standardized protocol. RMAs are defined as the presence of either RA or DR. Carotid atherosclerotic lesions including carotid intima-media thickness (CIMT), carotid atherosclerotic plaque and stenosis were assessed and compared between patients with and without RMAs based on Doppler ultrasound. The association of RMAs with carotid atherosclerotic lesions was analyzed by linear and binary logistic regression analyses.ResultsThe CIMT values in both male and female diabetics with RMAs were significantly greater than in those without RMAs after controlling for age (0.88 ± 0.21 vs. 0.77 ± 0.20 mm for men, p = 0.002; and 0.84 ± 0.19 vs. 0.76 ± 0.21 mm for women, p = 0.002). The prevalence of carotid plaque was also markedly higher in patients with RMAs than in those without RMAs after adjusting for age (54.3% vs. 23.9% for men, p < 0.001; 48.4% vs. 32.0% for women, p = 0.046). However, no significant difference was observed in the prevalence of carotid stenosis in either men or women with or without RMAs. After controlling for multiple confounding factors, RMAs were independently associated with increased CIMT in both men (β: 0.067,95% CI: 0.026–0.269, p = 0.018) and women (β: 0.087, 95% CI: 0.058–0.334, p = 0.005) with type 2 diabetes, and they were also closely associated with the presence of carotid plaque (OR: 2.17, 95% CI: 1.54–3.05, p < 0.001 for men; OR: 1.38, 95% CI: 0.91–2.08, p = 0.129 for women) in men with type 2 diabetes.ConclusionsRMAs were closely associated with early carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. Our results suggested that changes in retinal microvasculature may play a role in the pathogenesis of atherosclerosis and may be used as an indicator of early atherosclerosis in patients with type 2 diabetes.     

Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis

ObjectivesThe soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis.MethodsA cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen.ResultsPlasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p = 0.007) and IL-6 (p = 0.002), whereas sRAGE was negatively associated with those inflammatory markers (p = 0.001, p = 0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β = ?0.230, p = 0.037, β = 0.155, p = 0.045) and VCS (β = ?0.205, p = 0.049, β = 0.197, p = 0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03–1.25, p = 0.009), presence of diabetes (OR 13.4, 95% CI: 1.20–150.18, p = 0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05–5.11, p = 0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT > 1.0 mm and/or plaque formation).ConclusionsOur findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients.     

Is excessive daytime sleepiness a predictor of carotid atherosclerosis in sleep apnea?

ObjectiveTo elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers.MethodsOne hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS.ResultsForty-four patients had no OSA (apnea–hypopnea index AHI < 5 h^?1), 27 mild (5–15), 25 moderate (15–30) and 51 severe OSA (>30). The ESS significantly distinguished severe OSA from non-OSA patients (p = 0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation <90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p = 0.008), but not in the post-polysomnographic model after including respiratory variables.ConclusionEDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography.     

Relation of self-reported sleep duration with carotid intima-media thickness in a general population sample

ObjectivesAn association of sleep with cardiovascular disease has been suggested. We analyzed the association of sleep duration with carotid intima-media thickness (IMT) as measure of generalized atherosclerosis.MethodsIMT of the common carotid arteries was measured in 2437 participants of the Study of Health in Pomerania (SHIP). Participants indicated their daily sleep duration as sum of night and afternoon sleep.ResultsThere was a J-shaped association of sleep duration (5 to 11/12 h) with IMT. In this association, IMT values were lowest among subjects with an average sleep duration of 7–8 h (0.76 ± 0.15 and 0.79 ± 0.16 mm, respectively) but increased with shorter and, still more so, with longer sleep duration. Subjects with only 5 h sleep showed age- and sex-adjusted differences of 0.042 mm IMT (95% confidence interval 0.008–0.076 versus 8 h sleep). IMT values were still greater among subjects with 11–12 h sleep (adjusted differences versus 8 h sleep 0.084 mm [0.040–0.128] IMT). Further adjustment for lifestyle indicators, socioeconomic determinants, and biological variables attenuated these differences, but they remained significant.ConclusionsBoth longer and shorter sleep duration is associated with an increased risk of atherosclerosis. These findings support the hypothesis that sleep is related to cardiovascular disease.     

Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia

Background and objectivesDefects in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a highly atherogenic condition. The effect of different LDLR mutations on coronary heart disease (CHD) risk is insufficiently defined. We assessed carotid intima-media thickness (IMT), a surrogate marker of CHD, in relation to LDLR mutational class in FH.MethodsIn 436 Spanish FH patients (223 men and 213 women, age 44 ± 14 years) with known LDLR mutations, alleles were classified by standard criteria as null (n = 269), defective (n = 162), or undetermined (n = 5). LDLR defects were detected using a microarray (Lipochip^®) designed to uncover prevalent mutations in Spain and gene sequencing when no mutations were detected. Carotid IMT and plaque were assessed in FH patients and 268 healthy subjects.ResultsAll carotid measurements were increased in FH patients versus controls (p < 0.05), irrespective of genotype. After adjustment for gender and age, patients with null alleles compared with defective alleles had similar mean and maximum common carotid artery (CCA) IMT, but higher maximum IMT at any carotid segment, with median values (95% confidence interval) of 1.25 mm (1.19–1.31) and 1.11 mm (1.05–1.18), respectively. Multivariate analysis showed that null alleles were independently associated with maximum CCA-IMT (β = 0.09, p = 0.033) with an impact similar to that of gender (β = 0.10, p = 0.035).ConclusionsFH patients show advanced carotid atherosclerosis in relation to LDLR mutational class. The findings support the utility of genetic testing in FH beyond providing a secure diagnosis.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

Placenta growth factor expression in human atherosclerotic carotid plaques is related to plaque destabilization

Background and purposePlacenta growth factor (PlGF) mediates angiogenesis and inflammation, but its role in human atherosclerosis is unknown. This study was designed to test the hypothesis that PlGF-expression in human atherosclerotic carotid plaques is related to inflammation, vascularization and clinical plaque instability.MethodsThe expression of PlGF, C-reactive protein (CRP) and CD40L was analyzed with Western blots in carotid plaques of 60 patients. Cellular infiltration (CD68, CD3) and vascularization (von-Willebrand-factor) was assessed by immunohistochemistry.ResultsSymptomatic patients showed higher levels of PlGF than asymptomatic patients (115.4 ± 8.2 versus 83.6 ± 10.5 densitometric units (DU), p < 0.05) and higher grading for inflammatory cells and microvessels (CD3: 2.3 ± 0.1 versus 0.6 ± 0.1, p < 0.001, CD68: 2.4 ± 0.1 versus 0.8 ± 0.1, p < 0.001, microvessels: 2.3 ± 0.1 versus 1.5 ± 0.1, p < 0.01). PlGF-expression showed a positive correlation to the expression of CRP (r = 0.5, p < 0.001) and CD40L (r = 0.4, p < 0.01).ConclusionsPlGF-expression within human atherosclerotic lesions is associated with plaque inflammation and microvascular density, suggesting a role for PlGF in plaque destabilization and, thus, in clinical manifestation of the disease.