Metabolic syndrome and risks of carotid atherosclerosis and cardiovascular events in community-based older adults in China.

Sex Differences in Early Carotid Atherosclerosis (from the Community-Based Gutenberg-Heart Study)

To the Editor: Recently, an update from the Framingham study could not find uric acid to be an independent risk factor for cardiovascular disease.1 While serum uric acid levels correlated significantly with the risk for cardiovascular events and mortality in women, this relationship became insignificant after factoring for 11 additional variables including hypertension, body mass index, and diuretic use.1 Both the authors1 and an accompanying editorial2 interpreted these findings as showing that uric acid is not a true risk factor for cardiovascular disease and that it should not be routinely measured to assess cardiovascular risk. The careful analysis of the Framingham study is to be commended, but one must be cautious in the interpretation of the findings. While some epidemiologic studies such as the current one have not been able to show uric acid to be an independent risk factor for cardiovascular disease, other studies using multivariate analyses3 4 5 6 came to an opposite conclusion. Another recently completed study, the Worksite,7 also found uric acid to be an independent risk factor for cardiovascular events and mortality, especially in women. One might look for subtle explanations to account for the differences in these various studies, as Culleton et al1 have attempted, but most of the studies examined the very same variables. A more central issue is whether one should interpret the finding that a risk factor is not statistically independent to mean that it should not be considered biologically important. We would argue that this is not true in several situations. First, if the risk factors are causally linked, then one may not be able to show that they are independent of each other. For example, although smoking is a risk factor for mortality, it might no longer be independent if it is …

HDL-associated paraoxonase type 1 (PON1) can protect LDL and HDL against oxidative modification in vitro and therefore may protect against cardiovascular disease. We investigated the effects of PON1 levels, activity, and genetic variation on high density lipoprotein-cholesterol (HDL-C) levels, circulating oxidized LDL (OxLDL), subclinical inflammation [high-sensitive C-reactive protein (Hs-CRP)], and carotid atherosclerosis. PON1 genotypes (L55M, Q192R, -107C/T, -162A/G, -824G/A, and -907G/C) were determined in 302 patients with familial hypercholesterolemia. PON1 activity was monitored by the hydrolysis rate of paraoxon, diazoxon, and phenyl acetate. PON1 levels, OxLDL, and Hs-CRP were determined using an immunoassay. The genetic variants of PON1 that were associated with high levels and activity of the enzyme were associated with higher HDL-C levels (P values for trend: 0.008, 0.020, 0.042, and 0.037 for L55M, Q192R, -107C/T, and -907G/C, respectively). In addition to the PON1 genotype, there was also a positive correlation between PON1 levels and activity and HDL-C (PON1 levels: r = 0.37, P < 0.001; paraoxonase activity: r = 0.23, P = 0.01; diazoxonase activity: r = 0.29, P < 0.001; arylesterase activity: r = 0.19, P = 0.03). Our observations support the hypothesis that both PON1 levels and activity preserve HDL-C in plasma.

The goal of this study was to compare internal carotid artery (ICA) intima-media thickness (IMT) with common carotid artery (CCA) IMT as global markers of cardiovascular disease (CVD). Cross-sectional measurements of the mean CCA IMT and maximum ICA IMT were made on ultrasound images acquired from the Framingham Offspring cohort (n = 3316; mean age, 58 years; 52.7% women). Linear regression models were used to study the associations of the Framingham risk factors with CCA and ICA IMT. Multivariate logistic regression models and receiver operating characteristic (ROC) curve analysis were used to compare the associations of prevalent CVD with CCA and ICA IMT and determine sensitivity and specificity. The association between age and the mean CCA IMT corresponded to an increase of 0.007 mm/y; the increase was 0.037 mm/y for the ICA IMT. Framingham risk factors accounted for 28.6% and 27.5% of the variability in the CCA and ICA IMT, respectively. Age and gender contributed 23.5% to the variability of the CCA IMT and 22.5% to that of the ICA IMT, with the next most important factor being systolic blood pressure (1.9%) for the CCA IMT and smoking (1.6%) for the ICA IMT. The CCA IMT and ICA IMT were statistically significant predictors of prevalent CVD, with the ICA IMT having a larger area under the ROC curve (0.756 versus 0.695). Associations of risk factors with CCA and ICA IMT are slightly different, and both are independently associated with prevalent CVD. Their value for predicting incident cardiovascular events needs to be compared in outcome studies.

Bidirectional association between depressive symptoms and carotid atherosclerosis in community-based older adults in China

We assessed the effect of asymptomatic carotid atherosclerosis (CAS) on the development of cardiovascular diseases (CVDs) in a community-based population aged ≥55 years in China. A total of 1376 residents underwent CAS assessment by ultrasonography in July 2009. New CVD events, including stroke and coronary heart events, were collected at the follow-up survey at the end of 2014. After adjusting for baseline demographic characteristics and traditional CVD risk factors, the risk of CVD in patients with minimal CAS (mean common carotid artery intima-media thickness [CCA-IMT] ≥1 mm and no plaques), nonstenotic plaques (carotid stenosis <50%), and stenotic plaques (carotid stenosis ≥50%) was 0.8 (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.33-1.69), 2.0 (HR: 2.01, 95% CI: 1.24-3.25), and 3.1 (HR: 3.05, 95% CI: 1.62-5.74) times greater, respectively, than that of patients without CAS (CCA-IMT <1 mm and no plaques). Our findings provide direct evidence of the independent predictive value of the severity of asymptomatic CAS for the development of CVD in older Chinese adults.

Common carotid artery (CCA) intima-media thickness (IMT) is considered an atherosclerosis risk marker. Thickening of the intima-media complex is accelerated by vascular risk factors, in particular, by age and elevated blood pressure. Nonetheless, it also reflects intimal hyperplasia and intimal fibrocellular hypertrophy provoked by nonatherosclerotic mechanisms such as tensile wall stress. The aims of our study were to investigate the relationship between CCA IMT and the presence of vascular risk factors and to correlate CCA IMT with the degree of distal internal carotid artery (ICA) stenosis and the proximal CCA resistive index (RI), representative of wall stress. We assessed CCA IMT, the CCA RI, and the presence of carotid plaques in 1655 consecutive patients. Demographic features and vascular risk factors were collected. A positive linear relationship between mean IMT and age was observed (R(2) = 0.27; P < .001). In the multiple stepwise regression model, the presence of ICA plaques and vascular risk factors were all independently associated with higher IMT. When considering IMT values for left and right sides separately, there was an independent relationship between CCA IMT and the lateralized percentage of ICA stenosis (right IMT-right ICA percentage, R(2) = 0.10; P < .0001; left IMT-left ICA percentage, R(2) = 0.16; P < .0001) and the CCA RI, even after correcting for age and vascular risk factors. Risk factors for atherosclerosis and the percentage of ICA stenosis were independently associated with higher IMT values and an increase in the RI. The synergic action of risk factors may cause further deterioration of mechanical forces independent of carotid atherosclerosis.

We explored the associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) level and carotid atherosclerosis with all phenotypes and cardiovascular disease (CVD) events in Chinese older adults. A total of 1257 adults aged ≥55 years who were free of CVD were enrolled in this cohort study. Lipoprotein-associated phospholipase A2 level was evaluated in 3 categories: Lp-PLA2 < 175, 175≤ Lp-PLA2 < 223, and Lp-PLA2 ≥ 223 ng/mL. The highest level of Lp-PLA2 was independently associated with common carotid artery intima-media thickening (≥1.0 mm; odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.14-2.26) and carotid plaque (OR: 1.42, 95% CI: 1.01-1.99) in individuals without carotid artery stenosis. At the end of the 5-year follow-up, after adjustment for CVD risk factors and carotid atherosclerosis status, Lp-PLA2 had remained an independent predictor for myocardial infarction (MI; hazard ratio [HR]: 1.90, 95% CI: 1.02-3.55) and CVD death (HR: 1.78, 95% CI: 1.02-3.13). However, no association was found with stroke. Therefore, elevated Lp-PLA2 level in the older adults studied was associated with an increased risk of carotid atherosclerosis and MI and CVD mortality. Lipoprotein-associated phospholipase A2 assessment might be used for MI and CVD death risk prediction.

Introduction

OP0130 Independent Risk Factors for Cardiovascular Events in Male Patients with Gout: Results of the 7-Year Prospective Follow-Up Study

Background and Aim: Carotid intima-media thickness (IMT) is a well-studied phenotype of atherosclerosis in developed countries, however, there was only a few studies in developing countries. The aim of the study was to explore the relationships between carotid IMTs and prevalent cardio-metabolic diseases in Chinese. Methods: 1579 residents aged 40-74 years from three communities in northern Taiwan were recruited in 2010-2012. The far-wall intima-media thickness (IMTs) of the right and left common carotid arteries (CCAs), internal carotid arteries (ICA), and carotid bifurcation (BIF) were measured by B mode ultrasound. All participants were assessed for cardio-metabolic profiles and 10-year general cardiovascular risks by the Framingham Risk Score. Results: Correlation analyses showed that there were significant linear trends with age and estimated 10-year general cardiovascular risks for all segmental carotid IMTs. The linear trends were the strongest for CCA IMTs, followed by BIF IMTs, and the least for ICA IMTs, and stronger for the average IMTs of the right and left carotid arteries than one-sided IMTs alone. Male sex, central obesity, high BMI, high LDL-/HLD-C ratio, high blood pressure, and high blood sugar were significantly correlated with thicker carotid IMTs. Subjects affected with hypertension, diabetes mellitus (DM), metabolic syndrome, and cardiovascular diseases (CVDs) had significantly thicker carotid IMTs. After adjustment for traditional cardio-metabolic risk factors, subjects who had mean or maximum CCA or mean BIF IMTs &gt;= the 3rd quartiles had significantly higher likelihoods of having prevalent CVDs. The adjusted ORs were 2.13 (95% CI: 1.30-3.49), 1.73 (95% CI: 1.06-2.82), and 1.59 (95% CI: 1.01-2.51), respectively. The adjusted ORs were not significant for subjects who had elevated mean or maximum ICA or maximum BIF IMTs. Conclusions: Carotid IMTs were significantly correlated with most traditional cardio-metabolic risk factors. Among different segmental carotid IMTs, CCA IMTs demonstrated stronger associations with prevalent CVDs and DM. Carotid IMTs may be used as an intermediate marker of advanced vascular diseases in Chinese.

BackgroundEpidemiological studies have shown an inverse relationship between vitamin D levels and cardiovascular diseases. However, this does not infer a causal relationship between the two. Chronic kidney disease (CKD) patients have a high prevalence of vitamin D deficiency and carotid atherosclerosis. Therefore, in this study we have aimed to determine the association between serum 25-hydroxyvitamin D levels and carotid atherosclerosis in the CKD population.Methods100 CKD stage 3–4 patients were included in the study. Direct chemiluminesent immunoassay was used to determine the level of serum 25-hydroxyvitamin D. All subjects underwent a carotid ultrasound to measure common carotid artery intima-media thickness (CCA-IMT) and to assess the presence of carotid plaques or significant stenosis (≥50 %). Vitamin D deficiency was defined as serum 25-hydroxyvitamin D < 25 nmol/L. Abnormal CCA-IMT was defined as CCA-IMT ≥ 0.8 mm. Plaque was defined as a focal structure that encroaches into the arterial lumen of ≥ 0.5 mm or 50 % of the surrounding IMT value. Significant stenosis was defined as peak-systolic velocities ≥ 125 cm/s and end-diastolic velocities ≥ 40 cm/s.ResultsThe vitamin D deficiency and non-deficiency groups did not differ significantly in terms of abnormal CCA-IMT (P = 0.443), carotid plaque (P = 0.349), and carotid stenosis (P = 0.554). No significant correlation between serum 25-hydroxyvitamin D levels and CCA-IMT (P = 0.693) was found. On a backward multiple linear regression model, serum 25-hydroxyvitamin D levels was not associated with CCA-IMT, abnormal CCA-IMT, or plaque presence.ConclusionsNo important association between serum 25-hydroxyvitamin levels and carotid atherosclerosis was found in CKD patients.

Carotid atherosclerosis has been associated with increased risk of stroke and poorer cognitive performance in older adults. The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear. We studied 1975 Framingham Offspring Study participants free of stroke and dementia with available carotid ultrasound, brain MRI, and neuropsychological testing. We related common and internal carotid artery intima-media thickness and internal carotid stenosis to large white matter hyperintensity (>1 SD above age-specific mean), total brain volume, hippocampal volume, silent cerebral infarcts, and neuropsychological measures of verbal memory, executive function, and nonverbal memory measures. We observed that internal carotid artery intima-media thickness, but not common carotid artery intima-media thickness, was associated with higher prevalence of silent cerebral infarcts (OR, 1.21; 95% CI, 1.03-1.43; P<0.05), large white matter hyperintensity (OR, 1.19; 95% CI, 1.03-1.38; P<0.05), lower total brain volume (-0.05 per SD; P<0.05), and poorer performance in verbal memory (-0.06 per SD; P<0.05) and nonverbal memory measures (-0.08 per SD; P<0.01), but not with hippocampal volume. Internal carotid stenosis >or=25% was associated with a higher prevalence of large white matter hyperintensity (adjusted OR, 1.77; 95% CI, 1.25-2.53) and lower total brain volume (-0.11 per SD; P=0.042) but not with silent cerebral infarcts or hippocampal volume. Internal carotid stenosis >or=50% was associated with higher prevalence of silent cerebral infarcts (OR, 2.53; 95% CI, 1.17-5.44), large white matter hyperintensity (OR, 2.35; 95% CI, 1.08-5.13), and poorer performance on executive function (-0.39 per SD; P<0.05), but not with total brain volume or hippocampal volume. Carotid atherosclerosis markers were associated with MRI indices of brain ischemia and aging and with cognitive impairment in a community-based sample of middle-aged adults. Our data suggest that internal carotid artery intima-media thickness may be a better marker for cognitive impairment than common carotid artery intima-media thickness.

This study sought to determine the frequency of noncircular lumens in patients with significant carotid atherosclerotic disease and to evaluate the effect of noncircular lumens on stenosis measurement derived from angiographic projections. One hundred consecutive patients presenting with an internal carotid artery stenosis of at least 50% were imaged with spiral CT angiography. The transverse morphology of the diseased lumen was assessed on axial images, and the frequency of noncircular lumens was determined. In these cases, maximum intensity projection angiograms were reconstructed in standardized angiographic planes and in a plane selected according to the luminal obliquity, which was chosen to optimize the angiographic representation of the maximal stenosis. North American Symptomatic Carotid Endarterectomy Trial (NASCET) measurements were calculated from the maximum intensity projection images, and differences between values obtained from standard and optimized projections were recorded. Noncircular lumens were observed in 18 of 100 patients and consisted of elliptical and linear transverse profiles. The transverse orientation of the lumen in these cases ranged from +90 degrees to -87 degrees relative to the anteroposterior plane. An increase in the calculated NASCET stenosis was demonstrated when measurements were obtained from angiographic reconstructions obtained in the exact plane of the luminal obliquity compared with standard angiographic projections. As a result, the stenosis severity was upgraded from moderate to severe in 2 patients. Noncircular transverse luminal profiles are not uncommon and may introduce error into NASCET calculations obtained from standard angiographic projections.

The relationships among serum glucose, albumin concentrations and carotid atherosclerosis in men with spinal cord injury