Carotid atherosclerosis and vascular age in the assessment of coronary heart disease risk beyond the Framingham Risk Score

ObjectivesTo assess how ultrasound measurements of carotid intima-media thickness (CIMT) and plaque burden compare with the Framingham Risk Score (FRS) in a clinical setting.Methods and resultsIn a cross-sectional study, we determined CIMT and plaque in 409 asymptomatic, non-diabetic hyperlipidemic subjects (242 men, age 49 ± 11 years) who were assessed for risk factors and classified into FRS categories: 10-year risk ≤5% (n = 191), 6–20% (n = 176), and >20% (n = 42). Percentiles of CIMT and plaque height and regression equations of CIMT against age obtained in 250 controls subjects were used to define atherosclerosis and estimate vascular age, respectively. There was a wide dispersion of CIMT for each FRS category. CIMT values were discordant in 242 (59%) subjects, 80% of them showing more atherosclerosis than predicted. Smoking and the metabolic syndrome explained part of the discrepancies in the intermediate-risk group. Triglycerides, homocysteine, and lipoprotein(a) did not predict atherosclerotic burden. Mean vascular age was 14.5 years older than chronological age.ConclusionsCarotid atherosclerosis findings readjust FRS categories in many asymptomatic subjects. Both carotid atherosclerotic burden and vascular age may be used to refine CHD risk and tailor preventive treatment beyond the FRS.     

Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease

Background and aimsThe effectiveness of long-term cardiac rehabilitation and exercise training programs on metabolic parameters was evaluated in metabolic syndrome subjects with and without coronary heart disease (CHD).Methods and resultsFifty-nine CHD and 81 non-coronary patients with metabolic syndrome (59 ± 8 vs 56 ± 9 years) were identified retrospectively at entry into identical cardiac rehabilitation and exercise-training programs. Metabolic syndrome was defined using modified Adult Treatment Panel III criteria. Exercise training occurred approximately twice per week. Metabolic and exercise testing data were collected at baseline and after 12 months during the course of the program. Mean duration of cardiac rehabilitation and exercise training programs was over one year in both coronary and non-coronary patients (366 ± 111 vs 414 ± 102 days for CHD and non-coronary CHD cohorts respectively, p < 0.01). Significant improvements in bodyweight, body mass index, blood lipids, triglyceride/HDL ratio and exercise tolerance were noted in both cohorts. At the end of follow-up, 31% of CHD and 20% of non-CHD subjects no longer possessed diagnostic criteria for metabolic syndrome (p < 0.0001 and p < 0.001 respectively).ConclusionsA long-term cardiac rehabilitation program reduces metabolic syndrome prevalence in CHD patients and results in a similar improvement in risk factor control for metabolic syndrome patients without CHD.     

Recently postmenopausal women have the same prevalence of subclinical carotid atherosclerosis as age and traditional risk factor matched men

ObjectiveTo compare the prevalence of subclinical atherosclerosis between postmenopausal women and men of similar age early after the onset of menopause.MethodsIn the first part of this cross-sectional study 186 non-diabetic young postmenopausal women (n = 101, menopausal age ≤10 years) and men (n = 85) aged 40–60 years without overt CVD were consecutively recruited from the outpatients clinics of an academic hospital. Subclinical carotid atherosclerosis was assessed by high-resolution ultrasonography. The presence of carotid atherosclerosis was defined as either increased carotid intima-media thickness (IMT > 0.9 mm) and/or the presence of plaques. In the second part, 1:1 matching for age and traditional risk factors (hyperlipidemia, smoking, hypertension and BMI) was performed between men and women of this cohort resulting in a matched sub-sample of 76 subjects.ResultsBy multivariate analysis, gender was not an independent determinant of any measure of carotid atherosclerosis. In the matched sub-sample, carotid IMT and the number of segments with atherosclerosis did not significantly differ between women and men (0.734 ± 0.119 mm and 1.47 ± 1.6 versus 0.717 ± 0.138 mm and 1.47 ± 1.5, p = 0.575 and p = 0.999, respectively). Also, the prevalence of increased IMT (60.5% in both genders), carotid plaques and subclinical atherosclerosis (31.6% and 63.2% versus 28.9% and 65.8%, p = 0.803 and p = 0.811, respectively) was similar between men and women.ConclusionsThe prevalence and severity of carotid atherosclerosis was similar between men and young postmenopausal women matched for traditional risk factors. Whether these women may be better risk stratified irrespective of gender should be further assessed in prospective studies.     

Exercise training enhances autonomic function after acute myocardial infarction: A randomized controlled study

IntroductionHeart rate recovery, defined as the fall in heart rate during the first minute after exercise, is an indicator of autonomic function, and has been found to be an independent predictor of mortality after acute myocardial infarction. Exercise training has several well-known benefits in terms of cardiorespiratory fitness, modifiable cardiovascular risk factors and prognosis after acute coronary events. However, there are no randomized controlled studies in the literature evaluating the effects of exercise training per se, controlling for changes in medication and diet, on heart rate recovery. Thus, this study aims to assess the effects of exercise training on autonomic function in coronary artery disease patients recovering from acute myocardial infarction.MethodsThirty-eight patients following a first acute myocardial infarction participated in this prospective randomized clinical trial. Patients were randomized into two groups: exercise training or control. The exercise group participated in an 8-week aerobic exercise program, while the control received standard medical care and follow-up. Changes in hemodynamics at rest and at peak exercise (heart rate, systolic and diastolic blood pressure, and rate pressure product), dietary intake, cardiorespiratory fitness, and heart rate recovery were assessed.ResultsMedication and diet remained unchanged in both groups during the study period. The exercise-training group improved resting hemodynamics, particularly resting heart rate (from 68.0 ± 9.2 to 62.6 ± 8.7 bpm, p = 0.030) and systolic blood pressure (from 135 ± 7.1 to 125.6 ± 11.3 mmHg, p = 0.012), cardiorespiratory fitness (from 30.8 ± 7.8 to 33.9 ± 8.3 ml/min/kg, p = 0.016), and heart rate recovery (from 20 ± 6 to 24 ±5 bpm, p = 0.007). No significant changes were observed in the control group.ConclusionsExercise training improved autonomic function, assessed by heart rate recovery, resting heart rate and systolic blood pressure, in the absence of changes in diet or medication.     

Detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus

AimsThis study investigated autonomic nervous system function in subjects with diabetes during exercise and recovery.MethodsEighteen type 2 diabetics (age 55 ± 2 years) and twenty healthy controls (age 51 ± 1 years) underwent two 16-min bicycle submaximal ECG stress tests followed by 45 min of recovery. During session #2, atropine (0.04 mg/kg) was administered at peak exercise, and the final two minutes of exercise and entire recovery occurred under parasympathetic blockade. Plasma catecholamines were measured throughout. Parasympathetic effect was defined as the difference between a measured parameter at baseline and after parasympathetic blockade.ResultsThe parasympathetic effect on the RR interval was blunted (P = .004) in diabetic subjects during recovery. Parasympathetic effect on QT–RR slope during early recovery was diminished in the diabetes group (diabetes 0.13 ± 0.02, control 0.21 ± 0.02, P = .03). Subjects with diabetes had a lower heart rate recovery at 1 min (diabetes 18.5 ± 1.9 bpm, control 27.6 ± 1.5 bpm, P < .001).ConclusionsIn subjects with well-controlled type 2 diabetes, even with minimal evidence of CAN using current methodology, altered cardiac autonomic balance is present and can be detected through an exercise-based assessment for CAN. The early post-exercise recovery period in diabetes was characterized by enhanced sympathoexcitation, diminished parasympathetic reactivation and delay in heart rate recovery.     

Association between traditional cholesterol parameters, lipoprotein particle concentration, novel biomarkers and carotid plaques in retired National Football League players

ObjectivesWe assessed whether low-density lipoprotein particle concentration (LDL-P) and high-sensitivity C-reactive protein [hs-CRP] can identify subclinical atherosclerosis better than traditional cholesterol parameters in retired National Football League (NFL) players.BackgroundIt is not known whether LDL-P and the biomarker hs-CRP can identify subclinical atherosclerosis better than low-density lipoprotein cholesterol (LDL-C) or non-high-density-lipoprotein cholesterol (non-HDL-C) in retired NFL players, given high prevalence of metabolic syndrome in these players.MethodsCarotid artery plaque screening was performed with traditional lipids, LDL-P, and hs-CRP in 996 retired players. Logistic regression analyses comparing highest with the lowest quartile were performed.ResultsCarotid artery plaques were seen in 41%. LDL-C (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.06–2.59), non-HDL-C (OR 1.67, 95% CI 1.04–2.67), and LDL-P (OR 2.21, 95% CI 1.35–3.62) were associated with plaques in adjusted models. Among 187 retired players with metabolic syndrome, LDL-C (OR 1.40, 95% CI 0.53–3.72) was not associated with carotid plaques, whereas LDL-P (OR 3.71, 95% CI 1.16–11.84) and non-HDL-C (OR 2.63, 95% CI 0.91–7.63, p = 0.07; borderline significant) were associated with carotid plaques. hs-CRP (OR 1.13, 95% CI 0.71–1.79) was not associated with carotid plaques.ConclusionCarotid artery plaques were common in retired NFL players and were strongly associated with LDL-P, especially among those with metabolic syndrome. hs-CRP was not associated with carotid plaques in this cohort.     

The extent of heart rate reduction during hospitalization using beta-blockers,not the achieved heart rate itself at discharge,predicts the clinical outcome in patients with acute heart failure syndromes

AimIt has been uncertain whether patients with acute heart failure syndromes (AHFSs) benefit from a lower heart rate (HR) itself or from treatment for heart failure (HF) that reduces sympathetic tone with consequent HR reduction (HRR). The present study investigated the influence of HRR during hospitalization on the prognosis of AHFS patients.Methods and resultsIn 421 AHFS patients, we analyzed the relationship between HRR during hospitalization and the prognosis after discharge. During a mean follow-up period of 1.9 years, 76 and 55 patients died or were re-hospitalized for HF, respectively. Although HR at discharge did not influence cardiac events (hazard ratio [HR]: 1.00 [95% CI; 0.99–1.02], p = 0.22), the extent of HRR was a predictor of cardiac events (HR: 0.89 [0.84–0.96], p < 0.001). Kaplan–Meier analysis revealed that the cardiac event rate of the HRR-positive group (≥27 bpm reduction of HR from 114 ± 24 at admission to 65 ± 11 bpm at discharge) was significantly lower than that of the HRR-negative group (≤26 bpm (=median value) reduction of HR from 74 ± 14 to 71 ± 14 bpm). In the HRR-positive group, the cardiac event rate was significantly lower in patients receiving beta-blockers. Furthermore, the extent of HR change was an important predictor of cardiac events among other markers, compared with the change in systolic blood pressure or B-type natriuretic peptide.ConclusionThe HR itself at discharge was not associated with the prognosis, but the extent of HRR achieved by treatment of HF with beta-blockers was a strong predictor for the clinical outcome in AHFS patients.     

Atherosclerosis and arterial stiffness in obstructive sleep apnea--a cardiovascular magnetic resonance study

ObjectiveObstructive sleep apnoea (OSA) has been linked to cardiovascular risk factors, such as hypertension, and clinical cardiovascular endpoints. Our aim was to assess whether OSA is independently associated with atherosclerosis and vascular dysfunction as assessed by cardiovascular magnetic resonance (CMR).Methods58 patients with OSA and 39 matched control subjects without OSA underwent CMR of the aorta and carotid arteries. Carotid and aortic wall thickness and aortic distensibility were measured. Multi-weighted, high resolution CMR imaging was used for carotid atheroma characterization according to the American Heart Association (AHA) atheroma classification, modified for CMR.ResultsCarotid [1.47 ± 0.03 mm vs. 1.26 ± 0.05 mm, (P < 0.01)] and aortic wall thickness [2.95 ± 0.09 mm vs. 2.05 ± 0.07 mm, (P < 0.001)] were increased in patients with OSA compared to controls. Aortic distensibility was decreased in patients with OSA [3.62 ± 0.3 vs. 4.75 ± 0.2 mmHg^?1 × 10^?3, (P < 0.05)]. Prevalence of carotid plaque, average carotid atheroma class, and prevalence of high risk features of carotid atheroma were increased in patients with OSA (P < 0.005 for all). On multivariate analysis, Oxygen desaturation index (ODI) emerged as an independent predictor of carotid and aortic wall thickness, but not of aortic stiffness.ConclusionsOSA is associated with increased carotid and aortic atheroma burden and with advanced, high risk carotid atherosclerotic plaques, but not with aortic stiffening.     

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.     

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.     

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.     

Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies

ObjectivesTo address the relationship of rs1333049, the 9p21 variant showing the strongest association with coronary heart disease (CHD), with carotid plaques and plaque-free common carotid artery intima-media thickness (CCA-IMT) in older adults from 2 French population-based cohorts.MethodsWe genotyped for rs1333049, 4097 CHD-free participants including 3191 aged 65–86 years from the Three-City (3C) Study and 906 aged 59–71 years from the Vascular Aging Study (EVA). Plaque-free mean CCA-IMT and the presence of carotid plaques were assessed.ResultsIn multivariate analysis, each C allele copy of rs1333049 was associated with baseline carotid plaques (odds ratio (OR) = 1.24; 95% confidence interval (CI) = 1.13–1.36; p < 0.001) but not with baseline CCA-IMT (p = 0.19). Among the EVA participants, the C allele was associated with 4-year plaques progression (p = 0.04) but not with CCA-IMT progression.ConclusionThe chromosome 9p21 locus might influence CHD risk through carotid plaques development.     

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.     

Association of metabolic syndrome with carotid atherosclerosis in the young North Indian population

BackgroundMetabolic syndrome (MetS) and its components are associated with increased risk of stroke and cardiovascular disease. Relationship of MetS to carotid atherosclerosis has not been documented well in North Indian population.Aims(1) To determine the incidence of metabolic syndrome in asymptomatic healthy young North Indian population; (2) to evaluate individuals with MetS patients for carotid atherosclerosis by carotid duplex ultrasound examination; (3) to determine the significance of each component of MetS in relation to carotid atherosclerosis in these patients.Methods440 individuals in the age group of 25–50 years, asymptomatic for cardiac or cerebrovascular disease were screened for metabolic syndrome. 162 patients from a hospital-based population fulfilled the criteria for MetS (as per NCEP ATP III criteria). Duplex ultrasound (DU) examination of extracranial carotid vessels was performed on all the subjects. 112 age- and sex-matched controls were screened, and they underwent DU examination for comparison.ResultsHypertriglyceridemia was the commonest component seen in 79.6% of the MetS subjects, followed by central obesity seen in 74.6% subjects. Carotid atherosclerotic disease was observed in 21.6% of patients with MetS. Mild atherosclerosis (intima media thickness (IMT) >0.09 cm) was observed in 82.8% and 17.3% had plaques with mild stenosis (<50%) in the extracranial carotid arteries. Among patients of MetS with carotid atherosclerotic disease 82.6% had hypertriglyceridemia and 71.5% had 4 or more components for MetS. Among controls, five subjects (4.46%) had evidence of mild carotid atherosclerosis (IMT >0.09 cm) on DU. MetS was significantly associated with carotid DU abnormalities (increased IMT >0.09 cm) compared to controls (Fischer's exact test p < 0.0001). Univariate analysis showed the relationship of hypertriglyceridemia to carotid atherosclerosis (p = 0.03). On multivariate regression analysis none of the individual components of MetS contributed significantly to the presence of carotid atherosclerosis.ConclusionsMetS is common in asymptomatic healthy North Indian population, with hypertriglyceridemia being the commonest component of MetS in this population, which may be predictive of carotid atherosclerotic disease. Serum triglyceride estimation can serve as a screen for asymptomatic healthy subjects to select the target population for cerebrovascular disease prevention.     

Chronic HCV infection is a risk of atherosclerosis. Role of HCV and HCV-related steatosis

ObjectivesHCV and NAFLD are associated with atherosclerosis in general population. The prevalence of atherosclerosis in chronic hepatitis C (CHC) patients is unknown. We hypothesized that HCV per se and HCV-related steatosis could favour atherosclerosis. Thus, in CHC patients we assessed: (a) the prevalence of atherosclerosis; (b) the role of HCV, cardio-metabolic risk factors and hepatic histology.MethodsOverall, 803 subjects were enrolled: (A) 326 patients with liver biopsy-proven treatment naive CHC (175 with and 151 without steatosis); (B) 477 age and gender matched controls, including 292 healthy subjects without steatosis (B1) and 185 with NAFLD (B2). Carotid atherosclerosis (CA), assessed by high-resolution B-mode ultrasonography, was categorized as either intima-media thickness (IMT: >1 mm) or plaques (≥1.5 mm).ResultsCHC patients had a higher prevalence of CA than controls (53.7% vs 34.3%; p < 0.0001). Younger CHC (<50 years) had a higher prevalence of CA than controls (34.0% vs 16.0%; p < 0.04). CHC patients without steatosis had a higher prevalence of CA than B1 controls (26.0% vs 14.8%; p < 0.02). CHC with steatosis had a higher prevalence of CA than NAFLD patients (77.7% vs 57.8%, p < 0.0001). Viral load was associated with serum CRP and fibrinogen levels; steatosis with metabolic syndrome, HOMA-IR, hyperhomocysteinemia and liver fibrosis. Viral load and steatosis were independently associated with CA. Diabetes and metabolic syndrome were associated with plaques.ConclusionHCV infection is a risk factor for earlier and facilitated occurrence of CA via viral load and steatosis which modulate atherogenic factors such as inflammation and dysmetabolic milieu.     

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.     

Serum levels of osteocalcin in relation to glucose metabolism and carotid atherosclerosis in Chinese middle-aged and elderly male adults: The Shanghai Changfeng Study

BackgroundThe role of osteocalcin (OCN) in atherogenesis is unclear. We investigated the association between OCN and carotid atherosclerosis in Chinese middle-aged and elderly male adults and further determined whether OCN is independently associated with the carotid atherosclerosis in euglycemic subgroup.MethodsA total of 1077 male participants (mean age, 61.3 years) were enrolled from the Changfeng Study. A total of 638 subjects with normal glucose tolerance (NGT) were included in the subgroup analysis. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral carotid intima–media thicknesses (CIMTs) were measured using ultrasonography, and the presence of carotid plaques was assessed. The circulating OCN was measured using electrochemiluminescence immunoassay.ResultsOCN was 18.5 ± 7.5 ng/ml in this male population. Both impaired glucose regulation (IGR) and new diagnosed diabetes (NDD) groups had significantly lower OCN levels compared with the NGT group (17.7 ± 0.4 ng/ml, and 17.4 ± 0.6 ng/ml vs 19.2 ± 0.3 ng/ml, respectively). Multivariate linear stepwise regression analysis demonstrated that triglyceride (TG) (standardized β = − 0.065, p = 0.042) and fasting blood glucose (FBG) (standardized β = − 0.063, p = 0.034) were independently and inversely associated with serum OCN. In the NGT subgroup analysis, compared with subjects with OCN in the first quartile, subjects with OCN in the fourth quartile had decreased prevalence of carotid plaque. After adjusting for conventional CVD risk factors, male participants with OCN in the fourth quartile had a 0.57-fold decreased risk of carotid plaques relative to those in the lowest quartile.ConclusionThese results suggest that OCN is independently associated with carotid atherosclerosis in male individuals with NGT and that OCN may be implicated in not only glucose metabolism but also atherosclerosis.     

Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G-765C polymorphism in African-Americans: the Atherosclerosis Risk in Communities Study

BackgroundA hallmark feature of atherosclerosis is inflammation mediated by prostaglandins (PGs) catalyzed by the enzyme cyclooxygenase (COX). The present study explored whether the COX-2 G?765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atherosclerosis Risk in Communities (ARIC) Study.MethodsIncidences of CHD and stroke were identified through annual follow-up and hospital and death certificate surveillance. The study included 1488 incident CHD and 527 stroke events after an average of 14 years of follow-up. The frequency of the ?765C variant allele was markedly different between African-Americans and whites, therefore all analyses were performed separately by race. Due to the small number of persons with the ?765CC genotype, heterozygous and homozygous variant genotypes were combined for this analysis.ResultsThe COX-2 G?765C polymorphism was not a significant predictor of CHD in either racial group, but it was a significant predictor of incident stroke in African-Americans. After adjustment for age and gender, the hazard rate ratio for developing stroke for the CG+CC genotypes relative to the GG genotype was 1.34 (95% confidence interval [CI] 1.03–1.74, P = 0.03) in African-Americans. This result was essentially unchanged when established predictors such as smoking, diabetes and hypertension were added to the model (HRR 1.34, 95%CI 1.03–1.76, P = 0.03).ConclusionWe have found the COX-2 G?765C polymorphism to be a risk factor for incident stroke in African-Americans. This study provides additional evidence for utilizing inflammation-related genetic polymorphisms for identifying individuals at increased risk for stroke.     

Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a twenty years follow-up. A prospective study

ObjectivesTo investigate the extent of subclinical atherosclerosis in asymptomatic familial hypercholesterolemia (FH) patients using non-invasive images techniques.Patients, methods and resultsThe atherosclerotic burden of 36 molecularly defined FH patients (18 males, 45.7 ± 10.9 years) without evidence of cardiovascular disease receiving lipid-lowering treatment and 19 (47.8 ± 11.3 years) controls was investigated. Descending thoracic aorta magnetic resonance imaging (MRI) was performed in a 1.5 T equipment with T1 and T2 sequences to characterize atherosclerotic plaques and to measure aortic wall volumen. Carotid intima-media thickness (cIMT) and presence of plaques were measured using B-mode carotid ultrasound.Mean aortic wall volumen, cIMT and atherosclerotic plaques in aorta were significantly higher in FH cases (P < 0.001). A significant correlation between aortic wall volume and cIMT was observed (P < 0.01). Aortic MRI detected plaques in 94% and carotid ultrasound in 14% of cases. Lipid-rich plaques were observed only in FH cases (33%) and were associated with family history of premature coronary artery disease (P < 0.05).ConclusionsAsymptomatic middle-aged FH patients have significantly higher atherosclerotic burden than controls. cIMT has shown a significant correlation with aortic wall volume and MRI allowed the detection of lipid-rich plaques in FH subjects that were associated with family history of premature coronary artery disease.     

Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT)

BackgroundThe Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) showed that gemfibrozil significantly reduced major coronary events in men with known coronary heart disease (CHD). To better understand why therapy was especially effective with obesity, diabetes, and hyperinsulinemia, changes in body weight and plasma insulin were determined after 1 year of gemfibrozil or placebo therapy and related to changes in lipids and CHD events.ResultsWith gemfibrozil significantly more subjects lost weight (51.7% versus 38.6%, P < 0.0001) and significantly fewer subjects gained weight (42.5% versus 54.0%, P < 0.0001) than with placebo. Both a greater loss and smaller gain in weight with gemfibrozil were age-related and significant in subjects ≥66 years (median age), but not in younger subjects. Weight change was paralleled by changes in insulin. With gemfibrozil, CHD events were significantly reduced with weight loss (hazard ratio [HR], 0.61; 95% CI, 0.44–0.84; P = 0.002) and, particularly, with diabetes or hyperinsulinemia (HR, 0.53; 95% CI, 0.34–0.83; P = 0.006). In contrast, CHD events were not significantly reduced without weight loss (HR, 0.83; 95% CI, 0.62–1.12; P = 0.22).ConclusionsIn VA-HIT, gemfibrozil resulted in weight loss associated with reductions in insulin. With weight loss gemfibrozil produced a significant reduction in CHD events that did not occur in the absence of weight loss.