Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients With Severe Artery Calcification

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima‐media thickness (CCA‐IMT). Moreover, we studied the relationship between OPG levels and all‐cause and cardiovascular (CV) mortality during a 5‐year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C‐reactive protein, interleukin‐6, tumor necrosis factor receptor II (TNFRII), transforming growth factor‐β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA‐IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39–20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA‐IMT values (OR 6.56; 95%CI 1.06–40.6; P = 0.036). OPG levels above the median were associated with higher CCA‐IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84–72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA‐IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow‐up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA‐IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all‐cause mortality in CKD patients with advanced medial arterial calcification.     

Association of carotid hemodynamics with risk of coronary heart disease in a Taiwanese population with essential hypertension

BACKGROUND: The resistive index (RI) of the carotid artery is a hemodynamic parameter that depends on the degree of vascular resistance in hypertensive patients. The pulsatility index (PI) of the carotid artery was shown to be associated with microangiopathy in diabetic patients. In contrast to carotid intima-media thickness (IMT), no study has yet applied the carotid RI and PI to estimate coronary heart disease (CHD) risk. METHODS: Framingham risk scores (FRS) were determined for 62 patients (32 women; mean age 65 years (range 35-83)) with essential hypertension. Duplex sonography of the common carotid artery (CCA) was performed, with determination of RI, PI, and IMT. RESULTS: The mean FRS of all patients was 14.3% (range 1-30%), the mean IMT value of CCA was 0.89 +/- 0.23 mm, the mean RI was 0.71 +/- 0.07, and the mean PI was 1.46 +/- 0.39. FRS was found to have highly significant correlations with RI and PI (r = 0.47, P < 0.001 and r = 0.45, P < 0.001, respectively). The correlation between FRS and IMT was also significant (r = 0.41, P = 0.001). Multiple stepwise regression analysis showed that RI was an independent determinant of the risk of CHD. CONCLUSIONS: Although RI indirectly reflected the atherosclerotic process, the correlation between RI and CHD risk was comparable to the well-known correlation between cardiovascular event and carotid IMT. Hence, carotid RI can be used as a tool for risk stratification in Taiwanese patients with essential hypertension.     

Correlation between the intima-media thickness and Framingham risk score in patients with sleep apnea syndrome

Background

In the present study, we want to demonstrate the correlation between obstructive sleep apnea syndrome (OSAS) whose independent effect on carotid artery intima-media thickness (IMT) was demonstrated, with Framingham risk score (FRS) showing the overall cardiovascular risk.

Methods

IMT of the carotid artery was measured with ultrasonography and 10-year risk of coronary heart disease (CHD) was defined with FRS in 90 consecutive patients referred to our sleep clinic and who underwent polysomnography (PSG), with vascular risk factors and without a clinical atherosclerotic disease.

Results

IMT and FRS were found to be statistically significantly increased in the severe OSAS group compared to the other two groups. Carotid IMT was found to be significantly positively correlated with, apnea-hypopnea index (AHI), oxygen desaturation index (ODI) and time duration with oxygen saturation (SpO₂) <90%, and negatively correlated with minimum oxygen saturation at sleep (minimum SpO₂) and mean SpO₂. In control and mild OSAS group IMT and FRS have significantly positive correlation (r: 0.501, P: 0.027; r: 0.625, P<0.001), while in severe OSAS group no significant correlation was detected between IMT and FRS (r: 0.321, P: 0.06). In the regression analysis AHI and ODI were found to be an independent predictor of carotid IMT. ODI was found to have an independent effect on the progression of atherosclerosis.

Conclusions

Increased carotid IMT in severe OSAS group could not be explained with the classical risk factors. In this respect, FRS might be insufficient to determine correctly the cardiovascular risk and protection strategies against the disease in OSAS patients.KEYWORDS : Carotid artery, Framingham risk score (FRS), sleep apnea     

Determinants of carotid artery wall thickening in young patients with Type 1 diabetes mellitus

To investigate associations between early atherosclerosis and possible risk factors for it in young patients with established Type 1 diabetes mellitus (DM), we measured the combined intima-media thickness (IMT) of the common carotid arteries with high resolution ultrasound in 310 young patients (age ≤ 40 years, mean 27.9 ± 6.5) with a diabetes duration ≥ 2 years, and in two control groups of similar age (control 1:40 healthy subjects, control 2: 40 Type 1 DM recently diagnosed patients). Albumin excretion rate and lipids (total cholesterol and triglycerides) were measured and retinopathy and hypertension (systolic blood pressure > 140 or diastolic blood pressure > 90 mmHg) sought in the patients. Mean maximum IMT was 0.52 ± 0.06 mm in control group 1 and 0.50 ± 0.05 mm in control group 2 with a mean difference of 0.02 mm (95% CI: −0.01, 0.04). The more established Type 1 DM patients had a significantly greater IMT (0.57 ± 0.13 mm, p < 0.001) than both control groups. In a subgroup analysis, patients with microvascular diabetic complications (n = 99) had a significantly greater IMT (0.63 ± 0.17 vs 0.55 ± 0.10 mm, p < 0.001) than those without (n = 211). In a multiple linear regression analysis with a significance level of ≤ 0.10, the carotid artery IMT of our established diabetic patients was related to age, male gender, triglycerides and nephropathy, suggesting the latter as the main diabetes-specific risk for intima-media thickening in young Type 1 DM patients. © 1998 John Wiley & Sons, Ltd.     

The Relationship Between Flow‐Mediated Dilatation of the Brachial Artery and Intima‐Media Thickness of the Carotid Artery to Framingham Risk Scores in Older African Americans

The objective of this study was to investigate the relationship of flow‐mediated dilatation and intima‐media thickness (IMT) with coronary risk in African Americans (AAs). Endothelial dysfunction and IMT of carotid arteries are considered early steps in atherosclerotic disease process and have been used as surrogate markers of subclinical atherosclerosis. Data were collected on 106 AAs with a mean age of 64.0±6.6 years. Carotid artery IMT was measured with B‐mode ultrasonography, as was brachial artery diameter at rest, during reactive hyperemia, and after nitroglycerin. Percent change in flow‐mediated dilatation (%FMD) was defined as 100×(diameter during reactive hyperemia – resting diameter)/resting diameter. Percent change in nitroglycerin‐mediated dilatation (%NMD) was defined as 100×(diameter with nitroglycerin‐resting diameter)/resting diameter. The Framingham 10‐year risk score (FRS) was calculated for each patient using the National Cholesterol Education Program (NCEP) risk score calculator and participants were categorized into 3 groups with FRS as <10%, 10% to 20%, and >20%. Thirty‐eight participants had risk scores <10%, 26 had 10% to 20%, and 42 >20%. There was a significant inverse relation between %FMD and FRS (P<.0001) and between %NMD and FRS (P<.001). IMT was not statistically different among the risk groups. Endothelial dysfunction assessed by FMD significantly correlates inversely with FRS in AAs. FMD, an index of arterial compliance, appears to be a sensitive and reliable index of cardiovascular disease.     

Cardiovascular risk assessment and coronary artery calcification burden in asymptomatic patients in the initial years of hemodialysis

The specific tool for cardiovascular risk assessment in hemodialysis population has not yet been proposed, despite high prevalence of cardiovascular morbidity, and mortality in clinically asymptomatic patients. Coronary artery calcium score (CACS), as a reliable predictor of future cardiovascular events, might be a valuable approach. We sought to evaluate coronary artery calcification burden and its association with clinical and laboratory parameters in asymptomatic patients who recently initiated hemodialysis. The cross-sectional study included 60 asymptomatic patients receiving chronic hemodialysis for no longer than 48 months. CACS was assessed by cardiac computed tomography. Intima-media thickness (IMT) of both common carotid and femoral arteries were measured using ultrasonography. The mean total CACS was 160.50 (443). Patients' age correlated significantly with CACS (σ = 0.367; P = 0.004), carotid (σ = 0.375; P = 0.004) and femoral IMT (σ = 0.323; P = 0.013). Patients with CACS = 0 were significantly younger than patients with CACS >400: 52.4 ± 7.91 vs. 63.88 ± 8.37 years old, respectively (P = 0.034). In patients receiving dialysis for longer than 24 months CACS, femoral and carotid IMT were higher than in those dialyzed for less than 24 months; however, none has reached significance. There was a significant positive correlation between CACS and right (σ = 0.312; P = 0.018) and left (σ = 0.521; P < 0.001) femoral IMT, while not with carotid. CACS showed significant negative correlation with the serum iron (σ = ?0.351; P = 0.007). Calcification burden varies significantly in asymptomatic patients in early years of dialysis. It correlates with patients' age and tends to increase with dialysis vintage. Femoral IMT might be useful for cardiovascular risk stratification in asymptomatic patients who recently initiated hemodialysis.     

High Prevalence of Subclinical Atherosclerosis by Carotid Ultrasound among Mexican Americans: Discordance with 10‐Year Risk Assessment using the Framingham Risk Score

Background: Framingham risk scores (FRS) were validated in a mostly Caucasian population. Evaluation of subclinical atherosclerosis by carotid ultrasound may improve ascertainment of risk in nonwhite populations. This study aimed to evaluate carotid intima‐media thickness (cIMT) and carotid plaquing among Mexican Americans, and to correlate these markers with coronary risk factors and the FRS. Methods/Results: Participants (n = 141) were drawn from the Cameron County Hispanic Cohort. Carotid artery ultrasound was performed and cIMT measured. Carotid plaque was defined as areas of thickening >50% of the thickness of the surrounding walls. Mean age was 53.1 ± 11.7 years (73.8% female). Most were overweight or obese (88.7%) and more than half (53.2%) had the metabolic syndrome. One third (34.8%) had abnormal carotid ultrasound findings (either cIMT ≥75th percentile for gender and age or presence of plaque). Among those with abnormal carotid ultrasound, the majority were classified as being at low 10‐year risk for cardiovascular events. Carotid ultrasound reclassified nearly a third of the cohort as being at high risk. This discordance between 10‐year FRS and carotid ultrasound was noted whether risk was assessed for hard coronary events or global risk. Concordance between FRS and carotid ultrasound findings was best when long‐term (30‐year) risk was assessed and no subject with an abnormal carotid ultrasound was categorized as low risk by the 30‐year FRS algorithm. Conclusions: Integration of carotid ultrasound findings to coronary risk assessments and use of longer term prediction models may provide better risk assessment in this minority population, with earlier initiation of appropriate therapies.     

Effects of aging and sex on progression of carotid intima‐media thickness: A retrospective 6‐year follow‐up study

Aim: We retrospectively examined the relationship of aging, sex and risk factors to increased carotid intima‐media thickness (IMT) over a follow‐up period of 6 years in patients with multiple risk factors. Methods: Subjects were comprised of 463 patients (287 men, 176 women) with a mean age of 64 ± 0.4 years who had undergone carotid ultrasonography twice or more at intervals of 5 years or older. The mean follow‐up period was 6.0 ± 0.1 years. Results: Mean baseline IMT for all subjects was 1.40 ± 0.02 mm, and no significant difference was seen between sexes. Mean IMT after 6 years for all subjects was 1.84 ± 0.03 mm, and was significantly greater in men than in women. Mean annual increase in IMT (ΔIMT) for all subjects was 0.073 ± 0.005 mm/year, with a significant positive correlation between baseline age and ΔIMT (r = 0.11, P < 0.05), and ΔIMT was significantly greater in men than in women (0.087 ± 0.007 mm vs 0.050 ± 0.007 mm, P < 0.001). IMT increased with age in both men and women, but ΔIMT increased with age only in men. Multivariate analysis showed baseline age and diabetes mellitus as significant risk factors with baseline IMT as the objective variable. Age and sex represented significant risk factors with ΔIMT as the objective variable. Conclusion: Sex differences exist in the relationship between increases in IMT and age. Age, sex and diabetes mellitus represented the main risk factors.     

A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis

Abstract. Hamrefors V, Hedblad B, Engström G, Almgren P, Sjögren M, Melander O (Lund University, Malmö, Sweden). A myocardial infarction genetic risk score is associated with markers of carotid atherosclerosis. J Intern Med 2012; 271 : 271–281. Objective. To assess whether or not a genetic risk score that was previously shown to be associated with myocardial infarction (MI) and coronary artery disease (CAD) is also associated with markers of carotid atherosclerosis. Design. A total of 4022 middle‐aged subjects from the general Swedish population were genotyped and individually assigned a genetic risk score based on 13 single‐nucleotide polymorphisms (SNPs), previously associated with MI and CAD. The genetic score (Score‐MI) was then related to carotid bulb intima–media thickness (IMT), common carotid artery (CCA) IMT and to the occurrence of carotid plaques in the study population. Results. Score‐MI was associated with IMT of the bulb (P < 0.001) and the CCA (P < 0.001) in unadjusted analyses, and with IMT of the bulb after adjustment for cardiovascular risk factors (P = 0.003). The effect size of Score‐MI on IMT of the bulb was similar to that of LDL cholesterol. After adjustment for cardiovascular risk factors, Score‐MI was also associated with the occurrence of carotid plaques (odds ratio per quintile of Score‐MI = 1.11; 95% confidence interval 1.04–1.18; P = 0.001). In addition to SNPs with known effects on LDL levels, Score‐MI showed nominal associations with increasing systolic blood pressure and decreasing C‐reactive protein levels. Conclusions. This genetic risk score was independently associated with carotid bulb IMT and carotid plaques, providing evidence of an association with early markers of atherosclerosis. This might imply that the genetic MI risk conferred by the score is related to early atherosclerosis and that the risk score may identify at an early stage candidates at risk of developing intermediate phenotypes of atherosclerosis. Further studies should test whether or not assessing the genetic score could be valuable for early treatment decisions in these subjects.     

Insulin resistance, inflammation, and vascular disease in nondiabetic predialysis chronic kidney disease patients

Background:

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is not fully explained by traditional risk factors; hence, the interest in nontraditional risk factors such as inflammation and insulin resistance (IR). Though IR is shown in nondiabetic CKD, its association with vascular disease and inflammation in this population is unknown, and is what this study aims to investigate.

Hypothesis:

IR and inflammation are related to vascular disease in nondiabetic predialysis CKD patients.

Methods:

We studied carotid‐artery intima‐media thickness (IMT) and endothelial function (brachial artery flow mediated dilation [FMD]) in 35 nondiabetic predialysis patients with stage 3–5 CKD and 35 age‐ and gender‐matched controls. Insulin resistance was measured using the homeostasis model assessment for insulin resistance score (HOMA‐IR), inflammation by high‐sensitivity CRP (hsCRP), and their relationship with FMD and IMT.

Results:

Patients with CKD showed reduced FMD (3.34 ± 2.14% vs 5.27 ± 1.78%, P<0.001) and increased IMT (0.78 ± 0.22 mm vs 0.64 ± 0.16 mm, P = 0.003) compared with controls. The CKD patients had a higher HOMA‐IR (2.20 ± 1.08 vs 1.13 ± 0.64, P<0.001) and hsCRP (3.25 ± 5.47 mg/L vs 1.10 ± 1.85 mg/L [median ± interquartile range], P = 0.02). In the study population, HOMA‐IR was directly related to hsCRP. After adjusting for traditional risk factors, high HOMA‐IR and hsCRP were significantly related to decreased FMD (adjusted β = ? 0.44, 95% confidence interval [CI]: ? 1.55 to ? 0.08, P = 0.003 and adjusted β = ? 0.51, 95% CI: ? 0.51 to ? 0.15, P = 0.001) and increased IMT (adjusted β = 0.62, 95% CI: 0.54–1.90, P = 0.001 and adjusted β = 0.43, 95% CI: 0.08–0.57, P = 0.011), respectively.

Conclusions:

Subjects with systemic inflammation were more insulin‐resistant, and in nondiabetic predialysis CKD, IR and systemic inflammation were independently associated with endothelial dysfunction and atherosclerosis. © 2011 Wiley Periodicals, Inc. Dr. Debasish Banerjee and Dr. Alejandro Recio‐Mayoral are joint first authors. This study has been supported by grants awarded by the Spanish Society of Cardiology to Dr. A. Recio‐Mayoral and by the St. George's Charitable Foundation to Dr. D. Banerjee. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

     

Early detection of silent ischemia and diastolic dysfunction in asymptomatic young hypertensive patients

Background: There is an association between coronary artery disease (CAD) and increased carotid‐intima media thickness (IMT), a surrogate index of atherosclerosis. This association is poorly studied in asymptomatic subjects with risk factors of CAD. Aim: To study the relationship between carotid‐IMT, coronary flow reserve (CFR) and cardiac function in asymptomatic young hypertensive subjects. Methods: This study includes 82 asymptomatic young subjects with essential hypertension, and 78 healthy control subjects. Carotid‐IMT was assessed with B‐mode ultrasonography. Treadmill exercise test, CFR and echo Doppler study were performed for all subjects. Results: Hypertensive group had a significantly higher carotid‐IMT (0.91 + 0.13 vs. 51 ± 0.09, P < 0.01), and a significantly lower coronary flow velocity reserve (1.9 ± 0.44 vs. 3.2 ± 0.44, P < 0.003) than in control subjects, especially in those with stress induced myocardial ischemia. Multiple linear regression analyses shows that increased carotid‐IMT was related to a reduced CFR (r = ? 843, P < 0.001) and a lower diastolic function (E/e″, r = ? 512, P < 0.003) in asymptomatic hypertensives. In addition the carotid‐IMT showed a significant correlation with family history of hypertension in these subjects (r = 653, P < 0.002). Conclusion: Carotid‐IMT increases significantly in asymptomatic young hypertensive patients. It has a relationship with stress‐induced myocardial ischemia, decrease CFR and incipient diastolic dysfunction in those patients. It could be considered as an index for subclinical atherosclerosis and diastolic dysfunction in asymptomatic subjects with risk factors for CADs. (Echocardiography 2011;28:564‐569)     

Prehypertension is associated with atherosclerosis in Type 2 diabetes

Background: Prehypertension is a risk factor for hypertension, diabetes, and cardiovascular diseases. However, the association between prehypertension and atherosclerosis in Type 2 diabetes mellitus (T2DM) has not been evaluated. In the present study, we investigated the impact of prehypertension on atherosclerosis in T2DM. Methods: Patients (n = 930) with T2DM were recruited for the present study from the outpatient clinic of Shanghai Ruijin Hospital. The intima–media thickness (IMT) of the common carotid artery (CCA) was determined using ultrasound and brachial–ankle pulse wave velocity (baPWV) was determined by volume plethysmography to assess atherosclerosis. Results: Of the 930 patients with T2DM (mean age of 59 years), 167 were categorized as normotensive, 213 were prehypertensive, and 550 were hypertensive. Diabetic subjects with prehypertension had significantly higher CCA‐IMT and baPWV than those with normal blood pressure after adjustment for age and gender. Multiple logistic regression analysis revealed that, compared with normotension, prehypertension was a significant independent determinant of atherosclerosis (for maximum IMT ≥1.1 mm, odds ratio (OR) 2.10 and 95% confidence interval (CI) 1.28–3.44; for baPWV ≥1400 cm/s, OR 3.09 and 95% CI 1.78–5.36). Conclusion: Prehypertension is associated with atherosclerosis independent of conventional cardiovascular risk factors in T2DM patients. We speculate that maintenance of systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg may reduce the risk of atherosclerosis in T2DM.     

The combined effect of augmentation index and carotid intima-media thickness on cardiovascular risk in young and middle-aged men without cardiovascular disease

Carotid artery intima-media thickness (IMT) has been used as a surrogate marker of atherosclerosis and is related to cardiovascular risk. Indices of arterial stiffness are also associated with cardiovascular risk and atherosclerosis. The aim of this study was to assess the prognostic value of the combination of surrogate markers of cardiovascular disease measured non-invasively in subjects without cardiovascular disease. In this cross-sectional study, 81 young and middle aged males (39.2+/-6.3 years) without evidence of overt cardiovascular disease or diabetes mellitus were enrolled. High-resolution B-mode ultrasonography and pulse wave analysis were used to measure carotid artery IMT and augmentation index (AI), a measure of arterial stiffness. Framingham risk score (FRS) was used as an estimate of the risk for development of cardiovascular disease. Regional differences were observed in the carotid arteries' IMT regarding their relationship with FRS: combined (average from all sites) IMT and IMT in the carotid bulb (CB), but not in the common (CC) and internal carotid artery (IC), and AI showed significant increases of FRS by their tertiles. However, subjects with both AI and IMT at any site in the highest tertile (AI>15%, CC>0.65 mm, CB>0.8 mm, IC>0.65 mm) had an increased FRS compared to subjects with one or none of these parameters in the highest tertile. In conclusion, young and middle-aged men without overt cardiovascular disease with both high IMT and AI are in high cardiovascular risk, as assessed by FRS. Epidemiological studies are needed to further validate this combination.     

Carotid intima‐media thickness is increased in Turner syndrome: multifactorial pathogenesis depending on age,blood pressure,cholesterol and oestrogen treatment

Objective Carotid intima‐media thickness (IMT) may potentially supplement cardiovascular risk assessment in Turner syndrome (TS), where cardiovascular risk is high and appropriate risk stratification difficult. Knowledge of IMT in TS is scarce, and this study aimed to enhance insight into the cardiovascular risk marker. Design, Patients and Measurements IMT was cross‐sectionally assessed by ultrasonography of the common carotid artery (cIMT) and carotid bulb (bIMT) in TS (n = 69, age 40 ± 10 years) and age‐matched, healthy female controls (n = 67). Additional prospective IMT assessment was performed in TS over 2·4 ± 0·3 years. Metabolic biomarkers and 24‐h ambulatory blood pressure were also assessed. Results cIMT and bIMT (body surface area indexed) were increased in TS (P < 0·05) with 17–18% having IMTs that exceeded the 95th percentile of the controls (P < 0·05). Blood pressure, heart rate, glycosylated haemoglobin A1c and high‐density lipoprotein cholesterol were increased in TS, where 43% received antihypertensive treatment. cIMT decreased during follow‐up, coinciding with intensified cardiovascular risk prophylaxis, whereas bIMT was unchanged. In multiple regression analyses (R = 0·52–0·69, P < 0·05), baseline IMT in TS increased with age, blood pressure and cholesterol as well as in the presence of diabetes whilst IMT was inversely associated with duration of oestrogen replacement. In an analogue analysis, the prospective changes in cIMT (R = 0·37, P < 0·05) were beneficially influenced by antihypertensive treatment and oestrogen therapy and adversely by the presence of diabetes. Conclusion Carotid IMT was abnormal in TS and negatively influenced by age, metabolic biomarkers, blood pressure and short duration of oestrogen treatment. Attention to common cardiovascular and endocrine risk markers over more than 2 years appeared to influence IMT beneficially.     

Atherosclerosis in patients with biopsy‐proven giant cell arteritis

Objective

To examine the presence of atherosclerosis in a series of giant cell arteritis (GCA) patients attended to in a community hospital and to determine whether clinical features or steroid therapy might be associated with the development of atherosclerotic disease.

Methods

Forty consecutive patients diagnosed with biopsy‐proven GCA, periodically followed at the rheumatology outpatient clinic of Hospital Xeral‐Calde, Lugo (Spain), who had ended steroid therapy and had at least 3 years of followup were assessed for the presence of atherosclerosis by determination of the carotid intima‐media thickness (IMT) and carotid plaques using high‐resolution B‐mode ultrasound. Forty matched controls were also studied.

Results

GCA patients exhibited less carotid artery IMT than did matched controls (mean ± SD 1.01 ± 0.16 mm versus 1.13 ± 0.20 mm; P = 0.005; difference in means 0.12, 95% confidence interval 0.04–0.20). Patients who required steroid therapy for >2 years had greater mean ± SD carotid IMT (1.04 ± 0.17 mm versus 0.95 ± 0.15 mm) but the difference was not statistically significant (P = 0.10). A positive correlation between age at the time of the study and the carotid artery IMT in GCA patients was observed (r = 0.673, P < 0.001). However, adjusting for age, sex, and classic atherosclerosis risk factors, no significant correlation between carotid IMT and the routine laboratory markers of inflammation assessed at the time of disease diagnosis, disease duration, or cumulative prednisone dose was found.

Conclusion

The present study demonstrates that atherosclerotic macrovascular disease is not increased in patients with GCA.     

The relationship between cephalometric carotid artery calcification and Framingham Risk Score profile in patients with obstructive sleep apnea

Purpose

The morbidity rate of arteriosclerosis becomes clinically manifested as acute cardiovascular events. In the progress of atherosclerosis, the carotid artery calcifies and sometimes appears as a calcified mass on a cephalometric radiograph. This study was designed to evaluate cardiovascular risks according to the Framingham Risk Score (FRS) between subjects with and without visible carotid artery calcification on a cephalogram.

Methods

Subjects diagnosed with obstructive sleep apnea (OSA) were divided into two groups according to whether or not calcification was visible on a cephalometric radiograph in the carotid artery area, and the characteristic differences between the two groups were analyzed. The evaluated variables included age, BMI, apnea–hypopnea index (AHI), SpO₂, ESS, blood pressure, medication history, diabetes mellitus (DM), drinking, smoking, and lipid-related measurements. FRSs for stroke, general cardiovascular disease (GCD), and coronary heart disease (CHD) were calculated. Statistical analyses were performed (SPSS 18.0) with significance defined as a two-tailed p value less than 0.05.

Results

A total of 811 subjects completed the data collection (727 males, age 53.0?±?12.5 years, AHI 31.7?±?22.6, times/h). From FRSs, probabilities of a GCD, stroke, and CHD within 10 years were 16.0?±?9.7, 9.8?±?6.7, and 11.9?±?8.3 %, respectively. Some 84 subjects exhibited calcification in the carotid arterial area. Calcification subjects were higher GCD risk and older than subjects who had no identified calcification (20.3?±?10.1 vs 15.6?±?20.3 %, p?=?0.013, 58.8?±?11.4 vs. 52.3?±?12.5 years, p?<?0.001). Although there is no significant difference in OSA-related variables and FRSs, subjects with visible calcifications have higher prevalence of high blood pressure medication and DM (p?<?0.01).

Conclusion

While the presence of a calcified mass on a cephalometric radiograph is not diagnostic of atherosclerosis, this information indicates some cardiovascular risk.     

Lack of concordance between plasma markers of cardiovascular risk and intima-media thickness in patients with type 2 diabetes

Aim: Endothelial dysfunction, oxidative stress and systemic inflammation play an important role in the enhanced cardiovascular risk in diabetes. Carotid intima‐media thickness (IMT), a widely accepted marker of subclinical atherosclerosis, is known to be increased in patients with type 2 diabetes. The relationships between plasma markers of cardiac risk and carotid IMT are not well known. We therefore studied a group of patients with type 2 diabetes to evaluate the relationships between plasma markers of cardiac risk and carotid IMT. Design and patients: We measured carotid IMT and the levels of soluble endothelial adhesion molecules [sE‐selectin, intercellular cell adhesion molecule‐1 (sICAM‐1) and vascular cell adhesion molecule‐1 (sVCAM‐1)], C‐reactive protein (CRP) and 8‐isoprostane in 40 patients with type 2 diabetes without clinical macrovascular complications (HbA_1c < 10%, duration of diabetes < 12 years) and 25 healthy subjects. We then examined the correlations between these plasma markers, carotid IMT and various clinical and biochemical parameters. Results: Diabetic patients had higher plasma sE‐selectin (p = 0.03), sICAM‐1 (p = 0.05), CRP (p = 0.047) and 8‐isoprostane (p = 0.001) concentrations than control subjects. Mean IMT values were identical (0.63 ± 0.02 mm) in diabetic (range, 0.40–0.92 mm) and healthy subjects (range, 0.45–0.85 mm). In diabetic patients, stepwise multivariate analysis showed that HbA_1c and plasma glucose were independent predictors of sE‐selectin (r² = 0.19 and r² = 0.17, p < 0.01, respectively), whereas waist circumference and body mass index (BMI) were predictors of sICAM‐1 (r² = 0.27, p = 0.001 and r² = 0.22, p = 0.002, respectively). Waist circumference was the only predictor of CRP (r² = 0.2, p < 0.01), and systolic blood pressure was the only predictor of 8‐isoprostane (r² = 0.19, p = 0.006). In control subjects, similar analysis showed that plasma glucose and waist circumference were predictors of sE‐selectin and sICAM‐1, respectively (r² = 0.2, p < 0.05). Conclusions: These results indicate that some well‐controlled type 2 diabetic patients free of clinical macrovascular complications have elevated plasma markers of cardiovascular risk without having increased IMT. The elevation of plasma markers of endothelial cell activation (sE‐selectin and s‐ICAM‐1) or inflammation (CRP) and oxidative stress (8‐isoprostane) in diabetics vs. controls is distinct from and cannot be explained simply by differences in the burden of atherosclerosis as assessed by carotid IMT.     

Prognostic relevance of subclinical coronary and carotid atherosclerosis in a diabetic and nondiabetic asymptomatic population

Background

We sought to evaluate the incremental prognostic benefit of carotid artery disease and subclinical coronary artery disease (CAD) features in addition to clinical evaluation in an asymptomatic population.

Methods

Over a 6‐year period, 10‐year Framingham risk score together with carotid ultrasound and coronary computed tomography angiography were evaluated for prediction of major adverse cardiac events (MACE).

Results

We enrolled 517 consecutive asymptomatic patients (63% male, mean age 64 ±10 years; 17.6% with diabetes). Median (interquartile range) coronary artery calcium score (CACS) was 34 (0–100). Over a median follow‐up of 4.4 (3.4–5.1) years, there were 53 MACE (10%). Patients experiencing MACE had higher CACS, incidence of carotid disease, presence of CAD ≥50%, and remodeled plaque as compared with patients without MACE. At multivariable analyses, presence of CAD ≥50% (HR: 5.14, 95% CI: 2.1–12.4) and percentage of segments with remodeled plaque (HR: 1.04, 95% CI: 1.03–1.06) independently predicted MACE (P < 0.001). Models adding CAD ≥50% or percentage of segments with remodeled plaque resulted in higher discrimination and reclassification ability compared with a model based on 10‐year FRS, carotid disease, and CACS. Specifically, the C‐statistic improved to 0.75 with addition of CAD and 0.84 when adding percentage of segments with remodeled plaque, whereas net reclassification improvement indices were 0.86 and 0.92, respectively.

Conclusions

In an asymptomatic population, CAD and plaque positive remodeling increase MACE prediction compared with a model based on 10‐year FRS, carotid disease, and CACS estimation. In the diabetes subgroup, percentage of segments with remodeled plaque was the only predictor of MACE.     

Radiographic progression is associated with increased cardiovascular risk in patients with axial spondyloarthritis

Objectives: To compare the cardiovascular disease (CVD) risk between axial spondyloarthritis (axSpA) patients and matched controls, and to identify factors associated with increased CVD risk in axSpA patients.

Methods: This cross-sectional study enrolled 185 axSpA patients who fulfilled the Assessment for Spondyloarthritis (ASAS) criteria and 925 age- and sex-matched controls. None of the subjects had a previous history of CVD or diabetes mellitus. Traditional CVD risk factors were assessed and the 10-year CVD risk was calculated using the Framingham risk score (FRS). Estimated 10-year CVD risk was compared between axSpA patients and matched controls. Disease activity and radiographic progression in the sacroiliac joint and spine of axSpA patients were evaluated at the time of CVD risk assessment.

Results: High-density lipoprotein (HDL) cholesterol levels were lower in axSpA patients than in the matched controls (p?=?0.004); however, systolic blood pressure was higher (p?<?0.001). The FRS was 5.0?±?6.6% for controls and 6.3?±?8.7% for axSpA patients (p?=?0.046). Both the grade of sacroiliitis on X-ray and the number of syndesmophytes correlated with the FRS (p?=?0.009 and p?=?0.001, respectively), but disease activity variables did not. The FRS was significantly higher in axSpA patients with a greater number of syndesmophytes (p?=?0.035). Multivariate analysis identified the number of syndesmophytes as being independently associated with the FRS (p?<?0.001).

Conclusions: The FRS was higher in axSpA patients than in a matched general population. Radiographic progression in the spine was associated with a high estimated 10-year CVD risk.     

Prevalence of sleep apnea and cardiovascular risk factors in patients with hypertension in a day hospital model

Introduction: To identify patients at risk for obstructive sleep apnea (OSA) syndrome at a specialized hypertension center, we administered questionnaires and used respiratory polygraphy (RP). Results: We studied 168 patients (64.8% men and 35.2% women). Patients’ body mass index (BMI) was 34.7 ± 6.79 and Epworth Sleepiness Scale (ESS) scores were 8.01 for male and 8.92 for women (p = 0.69). RP recordings revealed AHI (Apnea-Hypopnea Index) of 18.03 ± 15.7, an ODI (Oxygen Desaturation Index) of 18.6 ± 15.2, and a time oxygen saturation <90% (%) of 20.8 ± 24.3. Around 44% of patients had an AHI of >15 events/h, and continuous positive airway pressure (CPAP) was recommended to 69 patients (41.07%). Pulse wave velocity (PWV) showed high values in AHI > 15/h (p = 0.050), and carotid intima-media thickness (IMT) did not correlate with AHI > 15; right IMT: 0.83 ± 1.3 versus 0.78 ± 0.13 mm (p = 0.41) and 0.82 ± 0.16 versus 0.78 ± 0.19 mm (p = 0.40). However, we find correlation with carotid plaque (p = 0.046). The ACC/AHA calculator revealed a gradual increase in the risk of cardiovascular events: 8.7% with AHI < 5/h, and 30.3% in severe OSA. Conclusions: In hypertension (HT) patients, RP revealed a high prevalence of OSA associated with carotid artery disease, high PWV, and increased cardiovascular risk.