Extent Of Carotid Atherosclerosis Research Articles

Association of habitual alcohol consumption with carotid atherosclerotic lesions: results from the Corinthia study

Abstract Introduction Alcohol is implicated in the pathophysiology of cardiovascular diseases. However, it is also believed to play a cardioprotective role if consumed in appropriate amounts. Purpose To assess the association between alcohol consumption and carotid atherosclerosis. Methods In the setting of the cross-sectional Corinthia study, volunteers filled in questionnaires regarding drinking habits and were characterized as social drinkers (SD) or habitual alcohol consumers (HAC). Furthermore, they underwent carotid ultrasonography examination to evaluate the carotid intima-media thickness (cIMT). Thickness of cIMT>1.5 mm or protrusion >50% compared to adjacent segments was considered as atherosclerotic plaque. Results HAC consumers were usually male (HAC: 61.1%, SD: 24.9%, p<0.001), smokers (HAC: 33.3%, SD: 23.5%, p<0.001) and frequently had a history of hypertension (HAC: 72.8%, SD: 67.5%, p=0.02) when compared to SD (Table 1). However, no significant differences were noted regarding other risk factors of atherosclerosis (Table). Notably, HAC had a greater extent of carotid atherosclerosis as demonstrated by an increased cIMT (HAC: 1.03±0.45mm, SD: 0.96±0.39mm, p<0.001) and carotid plaque burden (HAC: 27.7%, SD: 21.3%, p=0.004). Importantly, when taking into account the number of alcoholic drinks (in wine glasses), alcohol consumption of more than 1 wine glass resulted in significantly higher values of cIMT (1 wine glass: 1.00±0.42mm, >1 wine glass: 1.06±0.45mm, p=0.04) (Figure 1A) and extensive amount of carotid plaques (1 wine glass: 22.7%, >1 wine glass: 30.4%, p=0.02) when compared to consumption of 1 wine glass (Figure 1B). Conclusion Habitual alcohol consumption of more than one wine glass is associated with a higher carotid atherosclerotic burden. Figure 1 Funding Acknowledgement Type of funding source: None

Extent and characteristics of carotid plaques and brain parenchymal loss in asymptomatic patients with no indication for revascularization.

Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization. Sixty-four patients (aged 69±8years, 45% females) with carotid stenosis <70% based on Doppler flow velocity were enrolled in the study. Potential causes of cerebral damage other than atherosclerosis, including history of atrial fibrillation, heart failure, previous cardiac or neurosurgery and neurological disorders were excluded. All subjects underwent carotid computed tomography angiography, contrast enhanced ultrasound for assessment of plaque neovascularization and brain magnetic resonance imaging for measuring brain volumes. On multivariate regression analysis, age and fibrocalcific plaques were independently associated with lower total brain volumes (β=-3.13 and β=-30.7, both p<0.05). Fibrocalcific plaques were also independently associated with lower gray matter (GM) volumes (β=-28.6, p=0.003). On the other hand, age and extent of carotid atherosclerosis were independent predictors of lower white matter (WM) volumes. WM and GM have different susceptibility to processes involved in parenchymal loss. Contrary to common belief, our results show that presence of fibrocalcific plaques is associated with brain atrophy.

Ассоциация гетероплазмии мутаций митохондриального генома с ишемической болезнью сердца

Цель исследования. Усовершенствование алгоритма оценки генетической предрасположенности к развитию ишемической болезни сердца (ИБС), инфаркта миокарда (ИМ). Методика. Для оценки диагностической значимости степени гетероплазмии митохондриального было выполнено определение этого показателя у 100 здоровых лиц и 325 больных ИБС, в том числе у 225 больных ИБС с перенесенным инфарктом миокарда. Методом полимеразной цепной реакции в режиме реального времени (ПЦР-РВ) было проанализировано девять мутаций митохондриального генома, которые имеют корреляцию со степенью выраженности каротидного атеросклероза. Результаты. В настоящей работе проведена сравнительная оценка результатов генотипирования образцов ДНК участников исследования без клинических проявлений атеросклероза (условно здоровых лиц) и больных ИБС. В итоге была разработана математическая модель определения генетического риска ишемической болезни сердца, включающая анализ степени гетероплазмии четырех наиболее информативных генетических маркеров (m.15059G&gt;A, m.3256C&gt;T, m.12315G&gt;A и m.13513G&gt;A) и оценку полученных результатов с помощью ряда статистических методов. Данная модель объясняла не менее 60% вариабельности клинических проявлений атеросклероза (таких, как ИБС и ИМ) и не зависела от других факторов риска сердечно-сосудистых заболеваний. Заключение. На основе анализа суммарной мутационной нагрузки митохондриального генома была разработана математическая модель определения генетической предрасположенности к ишемической болезни сердца и инфаркту миокарда. Aim. To improve the algorithm for assessing the genetic predisposition to development of cardiovascular diseases. Methods. To evaluate the diagnostic value of the degree of mitochondrial heteroplasmy, this index was determined for 100 healthy individuals and 325 patients with coronary heart disease (CHD), including 225 CHD patients after myocardial infarction. The method of real-time polymerase chain reaction (RT-PCR) was used to analyze 9 mutations in the mitochondrial genome, which correlated with the extent of carotid atherosclerosis. Results. A mathematical model was developed to determine the genetic risk of CHD based on calculation of the total mutational load in the mitochondrial genome by mtDNA variants m.12315G&gt;A in MT-TL2 gene, m.15059G&gt;A in MT-CYB gene, m.3256C&gt;T in MT-TL1 gene, and m.13513G&gt;A in MT-ND5 gene. This model explained at least 60% of the variability in clinical manifestations of atherosclerosis and did not depend on other cardiovascular risk factors. Conclusion. Based on the analysis of total mutational load in the mitochondrial genome, a method was developed to assess the genetic risk for development of CHD and myocardial infarction.

Correlation among lipid parameters, pulse wave velocity and central blood pressure in young Korean population

ABSTRACTBackground: Central blood pressure is closely related to the important cardiovascular intermediate end points, such as vascular hypertrophy and extent of carotid atherosclerosis. Therefore it is prudent to study correlation among central aortic blood pressure, body composition, lipid profiles, and pulse wave velocity in population-based study. Consequently, we investigate the correlation between central aortic blood pressure and other risk parameters of hypertension such as body composition and lipid profile. Methods: We recruited 20 young participants diagnosed with hypertension as well as 30 without hypertension. The study used an X-SCAN PLUS 950 machine for measurement of overall body composition. Measurements of central blood pressure and carotid–femoral pulse wave velocity were carried out using SphygmoCor XCEL. Results: The hypertensive participants had significantly higher total weight without fat, body moisture mass, muscle mass, body mass index, basal metabolic rate, intracellular and extracellular water contents, protein and mineral contents along with brachial and central aortic blood pressures. In both hypertensive and non-hypertensive participants, central aortic diastolic blood pressure were significantly related to the lipid parameters. Conclusion: Overall, the correlations between central blood pressure, pulse wave velocity, and lipid profile in hypertensive and non-hypertensive participants were substantial.

Abstract MP010: A Prospective Study of DNA Methylation Age Acceleration and Incidence of Coronary Heart Disease, Heart Failure, and Peripheral Arterial Disease in the Atherosclerosis Risk in Communities (ARIC) Study

Introduction: DNA methylation patterns used to characterize rate of aging (i.e., epigenetic age acceleration) predict all-cause mortality independently of chronological age and traditional risk factors. It remains unclear how epigenetic age acceleration is associated with cardiovascular disease risk and subclinical atherosclerosis. Hypothesis: Higher epigenetic age acceleration is associated prospectively with greater risk of coronary heart disease (CHD), heart failure (HF), and peripheral arterial disease (PAD) and cross-sectionally with higher carotid intima-medial thickness (IMT). Methods: Age acceleration of blood was estimated by two published methods (Horvath and Hannum) using DNA methylation levels (Illumina 450K array) at 353 and 71 CpG sites in African Americans of the Atherosclerosis Risk in Communities study in 1990-95 (baseline). Among those without prevalent disease at baseline, Cox and linear regression models were used to estimate the association of age acceleration with incident cardiovascular events occurring through 2013 and with carotid IMT cross-sectionally at baseline. Results were stratified by follow-up time for HF due to violation of the proportional hazards assumption. Results: Participants [mean baseline age: 57 years (range: 47-72)] were followed prospectively for a mean 17 years. In fully-adjusted models (Figure), a 1 SD increment in Hannum epigenetic age acceleration was associated with 15-31% greater hazard of incident cardiovascular outcomes, except for HF in later follow-up. Associations using Horvath age acceleration were similar, except it was not associated with myocardial infarction. Cross-sectionally, a 1 SD increment in each age acceleration measure was associated with 0.01 higher baseline carotid IMT (both P ≤ 0.01). Conclusion: This study of African Americans provides evidence that epigenetic age acceleration is associated with greater risk of CHD, HF, and PAD events and higher extent of carotid atherosclerosis, independently of traditional risk factors.

Abstract T P156: Chronic Kidney Disease as a Risk Factor for Carotid Atherosclerosis : A Case Control Study

Background: Chronic kidney disease (CKD) increases risk of cardiovascular diseases, which might be mediated by facilitation of atherosclerosis. However, impact of CKD on progression of atherosclerosis has not been fully evaluated, and we sought to investigate associations between CKD and extent of carotid atherosclerosis. Methods: Between January 2009 and February 2013, we enrolled a consecutive series of 147 CKD patients and compared the same number of age, sex and vascular risk factor-matched 147 control subjects who visited our hospital during the same period. Carotid atherosclerosis was examined with MR angiography of internal carotid artery (ICA). The degree of stenosis of the internal carotid artery (ICA) in each patient was classified into 5 grades; (1) normal; (2) mild (&lt;50%); (3) moderate (50-69%) ;(4) severe (70-99%); (5) occlusion. Results: Mean age of the subjects was 72.2±8.7 years, and 208 were male (70.7%) among the total of 294 subjects. Significant stenosis of ICA (stenosis more than 50%) was more prevalent in CKD patients [odds ratio (OR) 6.7; 95% confidence interval (CI) 2.2-20.4, p=0.001). The presence of CKD was an independently risk factor for increasing the severity of stenosis of ICA (mild, OR 4.5, 95% CI 2.0-10.2; moderate, OR 3.9, 95% CI 1.3-22.4; severe, OR 12.0, 95% CI 4.3-34.6; occlusion, 14.1, 95% CI 2.1-92.2). Conclusion: In the current case-control study, we found that CKD is associated with incidence of significant carotid stenosis and increases the severity of carotid stenosis. Our results indicate that CKD should be treated as a new risk factor for carotid atherosclerosis.

THU0347 Central Blood Pressure in Patients with Ankylosing Spondylitis

BackgroundCentral (aortic) blood pressure (BP), which is the pressure exerted on the heart and brain, may be different from the pressure that is measured at the arm. Clinical studies have...

The Carotid Intima Media Thickness: A Predictor of the Clincal Coronary Events

The Carotid Intima-Media Thickness (CIMT) is a simple and an inexpensive tool which can be used to assess the cumulative effect of atherosclerotic risk factors and it is also an independent predictor of the future cardiovascular risk. Nevertheless, criticism has been raised throughout the scientific community, based on the observations which indicated a weak correlation between CIMT and coronary atherosclerosis. It has been suggested by the International Atherosclerosis Project, that the atherosclerotic process occurs at the same time in the carotid, cerebral and the coronary arteries. Measurement of the Carotid Intima-Media Thickness (CIMT) of the Common Carotid Artery (CCA) by B-mode ultrasound was found to be a suitable non-invasive method, to visualize the arterial walls and to monitor the early stages of the atherosclerotic process. This study sought to determine the usefulness of B-mode ultrasound as a non-invasive marker to examine the association between CIMT and the extent and the severity of coronary artery disease and its association with the cardiovascular risk factors, if any. A cross-sectional study was done among hundred cases and hundred age and sex matched controls who were in the age group of 30-65 years. The cases included those who had undergone coronary angiography. The controls included non-diabetic non-hypertensives with no cardiovascular risk factors. The CIMT was assessed by using a 7MHz linear array transducer. Fasting blood samples were collected for measuring the blood sugar and the lipid profiles. The statistical analysis was done by using the Student's t test and ANOVA and a p value of <0.001 was considered to be significant. The Average Carotid Intima Media Thickness (AVCIMT) was higher in the cases (0.90 vs 0.47 in controls, p<0.001, very highly significant). The AVCIMT was found to be higher in those with triple vessel disease (1.00mm) <double vessel disease (0.91mm) <single vessel disease (0.82mm) <normal coronaries (0.65mm). The easy applicability and the non invasive nature of B-mode ultrasonography make it suitable for use as a surrogate endpoint for measuring the atherosclerotic burden in people with cardiovascular risk factors. Even in this present study, we found a significant association between the extent of carotid atherosclerosis which was measured by B-mode ultrasound, and the presence, its extent, or the lack of coronary atherosclerosis which was documented by coronary angiography.

Relationship between circulating levels of RANTES (regulated on activation, normal T-cell expressed, and secreted) and carotid plaque characteristics: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study

To assess the relationship between regulated on activation, normal T-cell expressed and secreted (RANTES) and carotid atherosclerotic plaque burden and plaque characteristics. Gadolinium-enhanced magnetic resonance imaging (MRI) of the carotid artery was performed in 1901 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Wall thickness and volume, lipid-core volume, and fibrous cap thickness (by MRI) and plasma RANTES levels (by ELISA) were measured. Regression analysis was performed to study the associations between MRI variables and RANTES. Among 1769 inclusive participants, multivariable regression analysis revealed that total wall volume [beta-coefficient (β) = 0.09, P = 0.008], maximum wall thickness (β = 0.08, P = 0.01), vessel wall area (β = 0.07, P = 0.02), mean minimum fibrous cap thickness (β = 0.11, P = 0.03), and high-sensitivity C-reactive protein (β = 0.09, P = 0.01) were positively associated with RANTES. Total lipid-core volume showed positive association in unadjusted models (β = 0.18, P = 0.02), but not in fully adjusted models (β = 0.13, P = 0.09). RANTES levels were highest in Caucasian females followed by Caucasian males, African-American females, and African-American males (P < 0.0001). Statin use attenuated the relationship between RANTES and measures of plaque burden. Positive associations between RANTES and carotid wall thickness and lipid-core volume (in univariate analysis) suggest that higher RANTES levels may be associated with extent of carotid atherosclerosis and high-risk plaques. Associations between fibrous cap thickness and RANTES likely reflect the lower reliability estimate for fibrous cap measurements compared with wall volume or lipid-core volume measurements. Statin use may modify the association between RANTES and carotid atherosclerosis. Furthermore, RANTES levels vary by race.

Relationship of asymmetric dimethylarginine and homocysteine to vascular aging in systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is independently associated with accelerated atherosclerosis and premature arterial stiffening. Asymmetric dimethylarginine (ADMA) and homocysteine are mechanistically interrelated mediators of endothelial dysfunction and correlates of atherosclerosis in the general population. The aim of this study was to assess the relationship of ADMA and homocysteine to subclinical vascular disease in patients with SLE. One hundred twenty-five patients with SLE who were participating in a study of cardiovascular disease underwent clinical and laboratory assessment, carotid artery ultrasonography to detect atherosclerosis, and radial artery applanation tonometry to measure arterial stiffness. Neither ADMA nor homocysteine correlated with the presence or extent of carotid atherosclerosis. In contrast, ADMA was significantly related to the arterial stiffness index. Independent correlates of arterial stiffening included the ADMA concentration, the presence of diabetes mellitus, older age at the time of diagnosis, longer disease duration, and the absence of anti-Sm or anti-RNP antibodies. A secondary multivariable analysis substituting homocysteine for ADMA demonstrated comparable relationships with arterial stiffness (r(2) = 0.616 for homocysteine and r(2) = 0.595 for ADMA). ADMA and homocysteine are biomarkers for and may be mediators of premature arterial stiffening in patients with SLE. Because arterial stiffness has independent prognostic value for cardiovascular morbidity and mortality, its predictors may identify patients who are at increased risk of cardiovascular disease.

Urinary arsenic methylation capability and carotid atherosclerosis risk in subjects living in arsenicosis-hyperendemic areas in southwestern Taiwan

Long-term exposure to inorganic arsenic from artesian drinking well water is associated with carotid atherosclerosis in the Blackfoot Disease (BFD)-hyperendemic area in Taiwan. The current study examined the arsenic methylation capacity and its risk on carotid atherosclerosis. A total of 304 adults (158 men and 146 women) residing in the BFD-hyperendemic area were included. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Chronic arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE) and the duration of artesian well water consumption. Urinary levels of inorganic arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)] were determined by high performance liquid chromatography linked on-line to a hydride generator and atomic absorption spectrometry (HPLC-HG-AAS). The percentage of arsenic species, primary methylation index [PMI = MMA(V) / (As(III) + As(V)] and secondary methylation index [SMI = DMA(V) / MMA(V)] were calculated and employed as indicators of arsenic methylation capacity. Results showed that women and younger subjects had a more efficient arsenic methylation capacity than did men and the elderly. Carotid atherosclerosis cases had a significantly greater percentage of MMA(V) [%MMA(V)] and a lower percentage of DMA [%DMA (V)] compared to controls. Subjects in the highest two tertiles of PMI with a median of CAE > 0 mg/L-year had an odds ratio (OR) and a 95% confidence interval (CI) of carotid atherosclerosis of 2.61 and 0.98–6.90 compared to those in the highest two tertiles of PMI with a CAE = 0 mg/L-year. We conclude that individuals with greater exposure to arsenic and lower capacity to methylate inorganic arsenic may be at a higher risk to carotid atherosclerosis.

Insulin Resistance as a Risk Factor for Carotid Atherosclerosis

The independent contribution of insulin resistance to atherosclerosis is still under debate. We compared associations of 2 different indices of insulin resistance, the Homeostasis Model Assessment (HOMA) index and kITT from a short insulin tolerance test with carotid atherosclerosis. A total of 1771 middle-aged white patients were investigated. Intima media thickness (IMT) and extent of carotid atherosclerosis were quantified by ultrasound. HOMA was calculated and an insulin tolerance test was performed. HOMA and kITT were significant predictors for average carotid IMT (P<0.001). After adjustment for age and the components of the metabolic syndrome, HOMA still remained an independent predictor for IMT(avg) (P=0.02), whereas kITT failed to do so. HOMA and kITT were also predictive (P=0.004 and P=0.024) for carotid plaques and extent of carotid atherosclerosis (P<0.001). After adjustment for age and the components of the metabolic syndrome, neither HOMA nor kITT were independently predictive any more. Our results provide evidence that HOMA rather than kITT is associated with carotid atherosclerosis and that the association is largely explained by the clustered expression of the components of the metabolic syndrome.

Consumption of omega-3 fatty acids is not associated with a reduction in carotid atherosclerosis: The Genetics of Coronary Artery Disease in Alaska Natives study

Objective This study was designed to evaluate the relation between omega-3 fatty acid (FA) consumption and atherosclerosis. Background The hypothesis that omega-3 FAs protect against atherosclerosis has not been tested with objective measures of atherosclerosis. Methods A population-based sample of 1131 Alaskan Eskimos of age ≥18 underwent ultrasound assessment of carotid atherosclerosis. Those of age >35 ( N = 686) were included in the analysis. Diet was assessed by a food frequency questionnaire. Intimal–medial thickness (IMT) of the far wall of the distal common carotid arteries and plaque score (number of segments containing plaque) were assessed. Results Mean consumption of total omega-3 FAs was 4.76 g/day in those without and 5.07 g/day in those with plaque. In models adjusting for relevant risk factors, presence and extent of plaque were unrelated to intake of C20–22 omega-3 FAs or total omega-3 FAs. In contrast, the odds of plaque rose significantly with quartiles of palmitic ( p = 0.02) and stearic acid intake ( p = 0.04). The extent of plaque (or plaque score) was also associated with a higher percentage intake of palmitic acid ( p = 0.01). IMT was negatively associated with grams of C20–22 omega-3 FAs ( p = 0.05), total omega-3 ( p = 0.05), palmitate ( p = 0.03), and stearate ( p = 0.03) consumed. Conclusions Dietary intake of omega-3 FAs in a moderate-to-high range does not appear to be associated with reduced plaque, but is negatively associated with IMT. The presence and extent of carotid atherosclerosis among Eskimos is higher with increasing consumption of saturated FAs.

Endothelial Progenitor Cells, Cardiovascular Risk Factors, Cytokine Levels and Atherosclerosis – Results from a Large Population-Based Study

BackgroundEPC number and functionality are assumed to reflect the endogenous vascular repair capacity with the EPC pool declining in higher ages and being exhausted by unfavorable life-style and risk factors. This intriguing and clinically highly relevant concept, however, has so far been derived from small case-control studies and patient series.Methodology and Principle FindingsIn the population-based Bruneck Study EPC number and EPC-colony forming units (EPC-CFU) were assessed as part of the fourth follow-up evaluation (2005) in 571 and 542 subjects, respectively. EPC number declined with age (p = 0.013), was significantly lower in women (p = 0.006) and higher in subjects on statin, hormone replacement or ACE inhibitor/angiotensin-receptor blockers, and correlated positively with moderate alcohol consumption. Unexpectedly, a positive relation between EPC number and several vascular risk factors emerged. In a step forward multivariate linear regression analysis EPC number was independently related with SDF1α, MMP-9, triglycerides, alcohol consumption, and Hba1c. EPC-CFU in turn was related to SDF1α and diastolic blood pressure. Moreover, EPC number showed a significant positive association with the Framingham risk score (P = 0.001). Finally, there was an inverse association between EPC number and common carotid artery intima-media thickness (p = 0.02) and the carotid artery atherosclerosis score (p = 0.059).ConclusionsOur population-based data confirm the decline of EPC number with advancing age and lend first epidemiological support to a role of SDF-1α and MMP9 in EPC differentiation, mobilization and homing, but are conflict with the view that EPC number is unfavorably affected by cardiovascular risk factors. EPC number increases with the cardiovascular risk estimated by the Framingham risk score (FRS), which in the absence of similar changes for EPC-CFU. Finally, we demonstrate a significant inverse association between EPC number and extent of carotid atherosclerosis even though this association was only of moderate strength and not entirely consistent in other vascular territories.

Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension

Recent studies suggest that reductions in circulating endothelial progenitor cells (EPCs) may contribute to the development of atherosclerosis. However, whether reduced circulating EPCs contribute to cerebrovascular disease remains undefined. We tested the hypothesis that reduced circulating EPCs was associated with an increased burden of carotid atherosclerosis. The level of circulating CD34+/KDR+ EPCs and the extent of carotid atherosclerosis were determined in 30 patients with a history of atherothrombotic ischaemic stroke and 30 age- and sex-matched controls (mean age: 63+/-2 years; 63% men). Stroke patients, compared with controls, had significantly higher carotid mean maximum intima-media thickness (mmIMT) (1.08+/-0.05 versus 0.90+/-0.02 mm, P=0.002), prevalence of carotid plaque (60.0 versus 23.3%, P=0.004) and a lower number of circulating CD34+/KDR+ EPCs (235.7+/-45.5 versus 400.4+/-56.8 cells/mul, P=0.027). The circulating CD34+/KDR+ EPC count correlated negatively with carotid mmIMT (r=-0.50, P<0.001), and was an independent risk factor for increased carotid mmIMT>1 mm (odds ratio (OR): 7.71; 95% confidence interval (CI): 1.62-36.74, P=0.010) and the presence of carotid plaque (OR: 7.04; 95% CI: 1.95-25.43, P=0.003). Furthermore, stroke patients with low (<25th percentile of controls) as compared to those with normal CD34+/KDR+ EPC count had a significantly greater carotid mmIMT (1.21+/-0.07 versus 0.93+/-0.05 mm, P=0.005) and a significantly higher prevalence of carotid plaque (87.5% versus 28.6%; P=0.001). Our observations suggested that reduced circulating EPC may contribute to the progression of carotid atherosclerosis. Circulating EPC count may provide a novel marker for the burden of carotid atherosclerosis.

Antibodies Against Various Forms of Mildly Oxidized Low-Density Lipoprotein Are Not Associated With Carotid Intima-Media Thickness in Patients With Primary Hyperlipidemia

The carotid intima-media thickness (IMT) can reflect early atherosclerosis. Oxidative modification of low-density lipoprotein (LDL) leads to the formation of several immunogenic epitopes and different forms of antibodies against oxidized LDL (oxLDL). We investigated the possible relationship between autoantibody titers against various forms of mildly oxLDL and carotid IMT in patients (n=100) with primary hyperlipidemia. Three different types of mildly oxidized LDL-oxLDL(L), oxLDL(P), and oxLDL(D)-were prepared at the end of lag, propagation, and decomposition phases of oxidation, respectively. Similar types of oxLDL were also prepared from the same LDL preparations after inactivation of the LDL-associated platelet-activating factor acetylhydrolase (PAF-AH). These types were denoted as oxLDL(-)(L), oxLDL(-)(P), and oxLDL(-)(D). OxLDL types are primarily enriched in lysophosphatidylcholine (lyso-PC) due to hydrolysis of oxidized phospholipids (oxPL) by PAF-AH. OxLDL(-) types are mainly enriched in intact oxPL due to the inactivation of the LDL-associated PAF-AH before oxidation. IgG autoantibodies against all types of oxLDL were determined and IMT was evaluated ultrasonographically. IMT values were significantly associated with age, systolic blood pressure and serum triglyceride levels, whereas no correlation was found between IMT values and antibody titers against all types of either oxLDL or oxLDL(-). We suggest that autoantibodies against various types of mildly oxidized LDL enriched either in lyso-PC or in oxPL are not associated with the extent of carotid atherosclerosis. This supports the concept that extensively oxidized LDL enriched in aldehydes rather than mildly oxidized LDL may play a prominent role in the early stage of atherosclerosis.

The impact of visceral fat on multiple risk factors and carotid atherosclerosis in chronic haemodialysis patients.

There has been recent interest in the importance of visceral fat (VF) for the development of atherosclerosis. The purpose of this study was to examine associations between VF and multiple risk factors as well as the prevalence of carotid atherosclerosis in chronic haemodialysis patients. We classified 77 non-diabetic haemodialysis patients into 'low VF', 'middle VF' and 'high VF' groups after determining VF area using computed tomography. Systemic atherosclerosis was assessed from intima-media thickness (IMT), plaque score (PS) and stiffness parameter beta (stiffness-beta) measured by high-resolution B-mode ultrasonography. Compared with the low VF group, the high VF group exhibited (i) significantly higher fasting plasma insulin (11.0 +/- 6.8 vs 7.1 +/- 2.9 micro U/ml, P = 0.0061); (ii) significantly higher plasma triglycerides (141.8 +/- 94.0 vs 86.5 +/- 32.5 mg/dl, P = 0.0032); and (iii) significantly lower plasma high-density lipoprotein cholesterol (42.1 +/- 14.5 vs 53.0 +/- 15.7mg/dl, P = 0.0134). Moreover, the high VF group had a higher prevalence and extent of carotid atherosclerosis: IMT was 0.69 +/- 0.13 vs 0.61 +/- 0.12 mm (P = 0.0239), PS was 4.8 +/- 3.2 vs 2.4 +/- 3.6 (P = 0.0236) and stiffness-beta was 11.4 +/- 3.1 vs 8.5 +/- 3.0 (P = 0.0082) in the high and low VF groups, respectively. We show that VF is associated with the prevalence of carotid atherosclerosis as well as with hyperinsulinaemia and lipid abnormalities in chronic haemodialysis patients.

Biological gradient between long-term arsenic exposure and carotid atherosclerosis.

Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Diabetes mellitus was determined by oral glucose tolerance test, hypertension by mercury sphygmomanometers, and serum lipid profiles by autoanalyzers. Information regarding the consumption of high-arsenic artesian well water, cigarette smoking, and alcohol consumption was obtained through standardized questionnaire interviews. Logistic regression analysis was used to estimate the odds ratio and its 95% CI of carotid atherosclerosis for various risk factors. Three indices of long-term exposure to ingested arsenic, including the duration of consuming artesian well water, the average arsenic concentration in consumed artesian well water, and cumulative arsenic exposure, were all significantly associated with prevalence of carotid atherosclerosis in a dose-response relationship. The biological gradient remained significant after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, alcohol consumption, waist-to-hip ratio, and serum levels of total cholesterol and LDL cholesterol. The multivariate-adjusted odds ratio was 3.1 (95% CI 1.3 to 7.4) for those who had a cumulative arsenic exposure of > or =20 mg/L-years compared with those without exposure to arsenic from drinking artesian well water. Carotid atherosclerosis is associated with ingested inorganic arsenic, showing a significant biological gradient.

Characterization of premature atherosclerosis of carotid arteries in acromegalic patients.

Acromegalic patients have increased mortality from vascular diseases. Although atherosclerotic risk factors such as hypertension, diabetes mellitus and dyslipoproteinaemia are highly associated with acromegaly, the prevalence of premature atherosclerosis in acromegalic patients and its relationship to these risk factors have not been reported. We measured mean intima-media thickness (IMT) of the carotid arteries in 21 acromegalic patients without symptomatic atherosclerotic vascular disease, by ultrasound high-resolution B-mode imaging. In analysis 1, it was compared with the predicted mean IMT based on data from existing risk factors (age, male sex, dyslipoproteinaemia, hypertension, diabetes mellitus, smoking status) in 282 non-acromegalic subjects. In analysis 2, the mean IMT in the 21 acromegalic patients was compared with that in 42 non-acromegalic subjects matched for age, sex and the other atherosclerotic risk factors. We also analysed clinical characteristics between the acromegalic patients with and without the atherosclerosis. Mean IMT in 21 acromegalic patients was 0.92 +/- 0.21 (mean +/- SD) mm. It was significantly (P < 0.05) lower than the mean IMT (1.03 +/- 0.12 mm) predicted from their existing risk factors (analysis 1). It was also less than that in 42 non-acromegalic subjects matched for atherosclerotic risk factors (1.07 +/- 0.37 mm; P < 0.05) (analysis 2). Among the acromegalic patients, 10 patients (48%) had increased mean IMT (> or = 1.1 mm) and/or plaque lesions whereas the other 11 had no such atherosclerotic changes. In the patients without the atherosclerotic changes, plasma insulin-like growth factor-I (IGF-I) concentration was significantly (P < 0.01) higher, and the prevalence of hypertension was significantly (P < 0.05) lower than in those with the atherosclerotic changes. The extent of carotid atherosclerosis in the acromegalic patients was not higher than that in non-acromegalic subjects, considering their atherosclerotic risk factors. Increased concentration of IGF-I might be involved in the lack of susceptibility to atherosclerosis in some acromegalic patients.

Population-based study of age at menopause and ultrasound assessed carotid atherosclerosis: The Tromsø Study

Early menopause has been associated with higher prevalence and incidence of cardiovascular disease and death than late menopause, indicating that early loss of ovarian function and subsequent deficiency of estrogen may promote such diseases. No population-based studies have, however, examined the relation between age at menopause and atherosclerosis. We assessed the prevalence and the extent of carotid atherosclerosis by high-resolution B-mode ultrasound in 2588 postmenopausal women who participated in a population health survey. Information about age at menopause and menarche, parity, use of hormone replacement therapy, and prevalent diseases was collected, and cardiovascular risk factor levels were measured. Women with late menopause and women who ever had used postmenopausal estrogens had significantly less atherosclerosis than women with early menopause and those with never use of estrogen. This study provides further support for the hypothesis that estrogen protects women against cardiovascular disease.