Atherosclerosis In Multiple Vascular Beds Research Articles

Associations of Antibodies Targeting Periodontal Pathogens With Subclinical Coronary, Carotid, and Peripheral Arterial Atherosclerosis in Rheumatoid Arthritis.

Both periodontal disease and cardiovascular disease (CVD) are overrepresented in rheumatoid arthritis (RA). This study was undertaken to investigate the contribution of periodontal pathogens to CVD in RA. RA patients underwent assessments of coronary artery calcification (CAC), carotid intima-media thickness and plaque, and ankle-brachial index via computed tomography, ultrasound, and Doppler ultrasound, respectively. Sera were assayed for antibodies targeting Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans serotype B (Aa), and Aa-derived leukotoxin A (LtxA). Associations of antibodies against these periodontal pathogens with measures of atherosclerosis were explored using generalized linear models. Among 197 RA patients, anti-Pg was detected in 72 patients (37%), anti-Aa in 41 patients (21%), and anti-LtxA in 84 patients (43%). Adjusting for relevant confounders and reported tooth loss, the mean CAC score was 90% higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (19 units versus 10 units; P = 0.033). The adjusted odds of CAC ≥100 units were 2.23-fold higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (P = 0.040). Anti-Aa and/or anti-LtxA seropositivity was significantly associated with all other assessed measures of atherosclerosis except carotid plaque. Anti-Pg was not associated with any measure of atherosclerosis. Higher swollen joint count was associated with CAC exclusively in the group with anti-Aa and/or anti-LtxA. Immunoreactivity against Aa and/or its major virulence factor LtxA was associated with atherosclerosis in multiple vascular beds of RA patients and amplified the effect of swollen joints on coronary atherosclerosis, suggesting a role for treatment/prevention of periodontal disease in the prevention of CVD in RA.

Focal Aortic Vascular Injury Alters Remote Atherosclerotic Plaque Progression: An In Vivo Murine Mri Study

Background and Aims: Patients with atherosclerosis in multiple vascular beds frequently have poor prognosis1. Similarly, preclinical studies have demonstrated that myocardial infarction accelerates atherosclerosis2. Here we sought to investigate: i) whether focal aortic injury affects atherosclerosis progression in a remote vascular bed using in-vivo MRI; ii) whether there is a systemic inflammatory response and iii) whether pravastatin and minocycline treatment can alter remote disease progression.

Home blood pressure variability and subclinical atherosclerosis in multiple vascular beds: a population-based study.

The mechanism by which higher blood pressure (BP) variability causes cardiovascular events remains unclear. Experimental results indicate that alterations in vessel wall tension related to BP variability may initiate atherosclerosis through oscillatory shear stress. We examined associations of home BP variability with subclinical atherosclerosis at four anatomically distinct vascular beds. In a cross-sectional population-based study of 1033 Japanese (mean age, 64.0 years; men, 88.7%) without known cardiovascular disease, we defined SBP and DBP variability as variability independent of the mean (VIM) across self-measured home BP values during seven consecutive days and quantified coronary and aortic artery calcification (CAC and AAC) by computed tomography, carotid intima-media thickness (CIMT) by ultrasonography, and ankle-brachial index (ABI). In multivariable adjusted models including mean SBP, higher VIM of SBP was associated with CIMT greater than1.0 mm [relative risk (95% confidence interval) fourth versus first quartile, 1.71 (1.15-2.54)], AAC score greater than 0 [1.08 (1.02-1.15)], and ABI less than 1.1 [1.49 (1.12-1.97)], and linear trends were also statistically significant. However, there was no significant association between VIM of SBP and CAC score greater than 0. Meanwhile, higher VIM of DBP was associated only with AAC score greater than 0. The associations were similar when modeling subclinical atherosclerosis severity as continuous outcomes and were consistent across subgroups based on demographics, behavioural, and cardiovascular risk factors. Higher variability in home BP, particularly in home SBP, was associated with greater carotid, aortic, and peripheral but not coronary atherosclerosis burdens independent of the mean home BP.

Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men.

BackgroundSmoking is an overwhelming, but preventable, risk factor for cardiovascular diseases (CVD), although smoking prevalence remains high in developed and developing countries in East Asia.Methods and ResultsIn a population‐based sample of 1019 Japanese men aged 40 to 79 years, without CVD, we examined cross‐sectional associations of smoking status, cumulative pack‐years, daily consumption, and time since cessation, with subclinical atherosclerosis at 4 anatomically distinct vascular beds, including coronary artery calcification, carotid intima‐media thickness (CIMT) and plaque, aortic artery calcification (AoAC), and ankle‐brachial index. Current, former, and never smoking were present in 32.3%, 50.0%, and 17.7%, respectively. Compared to never smokers, current smokers had significantly higher risks of subclinical atherosclerosis in all 4 circulations (eg, odds ratios for coronary artery calcification >0, 1.79 [95% CIs, 1.16–2.79]; CIMT >1.0 mm, 1.88 [1.02–3.47]; AoAC >0, 4.29 [2.30–7.97]; and ankle‐brachial index <1.1, 1.78 [1.16–2.74]) and former smokers did in carotid and aortic circulations (CIMT >1.0 mm, 1.94 [1.13–3.34]; and AoAC >0, 2.55 [1.45–4.49]). Dose–response relationships of pack‐years and daily consumption, particularly with CIMT, carotid plaque, AoAC, and ankle‐brachial index, were observed among both current and former smokers, and even a small amount of pack‐years or daily consumption among current smokers was associated with coronary artery calcification and AoAC, whereas time since cessation among former smokers was linearly associated with lower burdens of all atherosclerotic indices.ConclusionsCigarette smoking was strongly associated with subclinical atherosclerosis in multiple vascular beds in Japanese men, and these associations attenuated with time since cessation.

Abstract 11: Compliance With Risk Factor Optimization and Medical Therapy in Patients With Peripheral Vascular Disease (Peripheral Artery and Ischemic Cerebrovascular Disease) Compared to Ischemic Heart Disease.

Background: Cardiovascular disease (CVD) is a systemic process with patients developing atherosclerosis in multiple vascular beds including ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD) and peripheral artery disease (PAD). PAD and ICVD are associated with increased risk of subsequent myocardial infarction, stroke and death. Medical management and risk factor optimization are recommended for all patients with CVD. Compliance with measures in patients with ICVD and PAD compared to IHD is not known. Methods: In a large national cohort, we identified 1,242,015 patients with cardiovascular disease (CVD) receiving care in 130 Veterans Affairs facilities between 10/1/2013 and 9/30/2014. CVD was defined as the presence of IHD, PAD, or ICVD. We assessed the frequency of compliance with performance measures in patients with IHD (with or without concomitant PAD or ICVD), PAD only, ICVD only, and PAD+ICVD groups. We compared compliance with hypertension control (BP &lt;140/90 mmHg), diabetes control (HbA1C&lt;7.0% among diabetics), and the use of statin therapy between IHD and PAD, ICVD, or PAD+ICVD groups. A composite of all 3 measures (BP control, statin use, HbA1C &lt;7% among diabetics) termed optimal medical therapy (OMT) was also compared between groups. Multivariate logistic regression was performed with IHD group as the referent category. Results (Table): IHD patients comprised 989,380 (79.7%), PAD only 70,404 (5.7%), ICVD only 163,730 (13.2%) and PAD + ICVD 18,501 (1.5%) of the cohort. Compliance with most measures (hypertension control, statin use) as well as OMT was lower for PAD or ICVD patients compared with IHD patients with minimal differences between IHD and PAD +CVD group. Overall, only 32.3%-41.8% received OMT (i.e. met the composite measure). Conclusions: Compliance with OMT was low in all patients. Patients with PAD or ICVD were less likely to receive OMT compared with IHD. Our results suggest potential for improvement in OMT for all CVD patients especially those with PAD and ICVD.

Imaging of Coronary Arteries Aid in Prevention of Atherosclerosis and Clinical Coronary Heart Disease

Prevention of progression of atherosclerosis is the best approach to reduce incidence of myocardial infarction, sudden coronary heart disease (CHD) death, stroke and peripheral vascular disease. Research over the past 40 years has identified the risk factors for atherosclerotic disease, noninvasive methods for measuring the extent of atherosclerosis in multiple vascular beds and very efficacious therapy to reduce the level of risk factors and prevent cardiovascular diseases. Cardiovascular incidence and death rates have declined. Nevertheless, rates of CHD and other vascular disease remain much higher in many countries and within select regions of certain countries than necessary. Prevention of atherosclerosis depends on 4 key steps: 1) a much more aggressive effort to lower modifiable risk factors, especially apolipoprotein-B (ApoB)-containing lipoproteins, low density lipoprotein (LDL) particles, LDL cholesterol, blood pressure, obesity, and smoking during adolescence and young adult years; 2) identify and treat elevated ApoB lipoproteins, diabetes and smoking cessation of very high risk young adults as early as possible; 3) use of imaging to identify atherosclerosis of coronary and other arteries for appropriate segments of the adult population and treatment of risk factors for those with identifiable atherosclerosis; and 4) improved approaches to deliver prevention of cardiovascular disease to large numbers of asymptomatic individuals identified by non invasive imaging to maximize adherence to therapies. The major missing piece is better methods to identify vulnerable coronary plaques on the verge of an atherothrombotic transition and better treatments to prevent “acute” events. However, the four steps above will still lead to very substantial reductions in CHD incidence and mortality.

Circulating lymphotoxin β receptor and atherosclerosis: Observations from the Dallas Heart Study

Objective Lymphotoxin β receptor (LTβR), a member of the tumor necrosis factor superfamily, binds ligands expressed by activated lymphocytes. Interruption of LTβR signaling improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTβR and examined its association with atherosclerosis phenotypes in a population-based sample. Methods and results Plasma LTβR was measured by ELISA in 3215 subjects enrolled in the Dallas Heart Study. Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) and abdominal MRI measurements of aortic plaque (AP) ( n = 2252) and aortic wall thickness (AWT) ( n = 2265). We analyzed associations between LTβR and atherosclerosis using multivariable logistic and linear regression methods. Higher levels of LTβR associated with most traditional cardiovascular risk factors, multiple inflammatory markers, and markers of cardiac injury. Univariable analyses demonstrated significant associations of LTβR with CAC, AP, and AWT ( p < 0.0001 for each). In multivariable models adjusted for traditional risk factors, the 4th vs. the 1st quartile of LTβR remained associated with prevalent CAC, AP, and increased AWT (all p < 0.05). Similar associations were observed when LTβR was modeled as a log-transformed continuous variable. Conclusion LTβR levels are independently associated with atherosclerosis in multiple vascular beds. These findings support further investigation of the lymphotoxin/LTβR pathway in atherosclerosis.

Blood Pressure and Vascular Calcification

The aim of this study was to determine the associations between the presence and extent of calcified atherosclerosis in multiple vascular beds and systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, isolated systolic hypertension, and hypertension. A total of 9510 patients (42.5% women) underwent electron beam computed tomography scanning as part of a routine health maintenance screening. At the same visit, blood pressure was measured with the participant in the seated position using a mercury sphygmomanometer. Mean age was 58+/-11.4 years, and body mass index was 27.1+/-4.5. The prevalences of any calcification in the carotids, coronaries, subclavians, thoracic aorta, abdominal aorta, and iliacs were 31.9%, 57.2%, 31.7%, 37.0%, 54.3%, and 48.8%, respectively. In separate multivariable logistic models containing traditional cardiovascular disease risk factors, pulse pressure and systolic blood pressure were significantly associated with the presence of calcification in all of the vascular beds except the iliacs and subclavians, respectively, with pulse pressure having stronger magnitudes of the associations for most of the vascular beds. Age-stratified analyses indicated that these associations were stronger in those >60 years of age compared with subjects <60 years of age, and sex-stratified analyses demonstrated that men had a greater association compared with women. Also, the magnitudes of the associations for isolated systolic hypertension were, in general, larger than those for hypertension. Pulse pressure and isolated systolic hypertension are robust and important correlates for calcified atherosclerosis in different vascular beds. Isolated systolic hypertension may be clinically relevant in diagnosing or preventing calcified atherosclerosis.

The associations between visceral fat and calcified atherosclerosis are stronger in women than men

BackgroundPrevious studies have found a significant association between body mass index (BMI) and coronary artery calcium (CAC). Little is known about whether body fatness is linked with atherosclerotic calcium (AC) in the non-coronary vasculature. Accordingly, this study tested the hypothesis that there would be significant associations between CAC and AC in the non-coronary vasculature and BMI, visceral fat (VF), and percent body fat (BF%). MethodsSubjects (n=1160; mean age 57 years; 55% men) underwent electron beam computed tomography (EBCT) screening for AC in the carotid, coronary, thoracic and abdominal aorta, and iliac arteries. Visceral fat and BF% were measured using EBCT and electrical bioimpedance analysis, respectively. ResultsIn sex-stratified models adjusted for CVD risk factors, there were significant associations among both sexes between 1-SD increments of BMI, BF% and VF and the presence of CAC (p<0.01) as well as for quartiles of BMI and VF and prevalent CAC. Higher levels (tertiles) of BF% and VF were significantly associated with higher amounts of both abdominal aortic calcium (OR=1.90, 1.57 with p=0.02, 0.05 in females and males, respectively) and CAC. ConclusionsMeasures of body morphology are significantly associated with AC in the coronary arteries and abdominal aorta. Of the measures studied, VF appears to be the most relevant by having the most consistent and stronger magnitudes of association, especially in women. These results suggest that VF may be more relevant in women than men with respect to the presence and extent of atherosclerosis in multiple vascular beds.

Abstract 5544: Lymphotoxin β Receptor is Associated with Atherosclerosis in the Dallas Heart Study

Introduction: Lymphotoxin β receptor (LTBR), a member of the tumor necrosis factor receptor family, is expressed by activated lymphocytes. Blocking LTBR improves autoimmune diseases and alters lipid homeostasis. We assayed circulating LTBR and examined its association with atherosclerosis in multiple vascular beds. Methods: Plasma LTBR was measured in 3215 subjects aged 30–65 enrolled in the Dallas Heart Study using an experimental ELISA assay (Biosite, Inc). Atherosclerosis was assessed using CT measurements of coronary calcium (CAC) (n=2462) and abdominal MRI measurements of aortic plaque (AP) (n=2252) and aortic wall thickness (AWT) (n=2265). We analyzed LTBR and atherosclerosis with uni- and multivariable logistic and linear regression methods. Results: The study cohort had median age 43; 44% women; and 70% non-white subjects. Higher levels of LTBR were associated with traditional cardiovascular risk factors and other inflammatory markers. Univariable analysis demonstrated modest associations with CAC (Spearman rho = 0.11, p&lt;0.0001) and AWT (rho=0.16, p&lt;0.0001). In multivariable models adjusted for traditional risk factors, the 4 th vs. the 1 st quartile of LTBR was associated with CAC &gt; 10 (adjusted OR 1.4, 95% CI 1.01–1.95; Figure ); AP (OR 1.4, 95% CI 1.1–1.8; p=0.02); and increased AWT (β = 0.06, p&lt;0.0001). Similar associations were observed when log transformed LTBR was used as a continuous variable. Conclusion: LTBR levels are independently associated with atherosclerosis in multiple vascular beds. These findings suggest a potential role of activated lymphocytes in the pathogenesis of atherosclerosis and warrant further investigation.

Aortic Plaque Imaging and Monitoring Atherosclerotic Plaque Interventions

The atherosclerotic process that results in coronary artery disease (CAD) is recognized to be a generalized process that may involve the entire vasculature. The association between CAD and atherosclerotic plaques in the thoracic aorta has often been reported using transesophageal echocardiography. An autopsy study showed plaques in the abdominal aorta, but not in the thoracic aorta, to be severe in patients with cardiac events. However, studies evaluating an association between abdominal aortic plaques and CAD are scarce. Recently, magnetic resonance imaging (MRI) has become a useful tool for the noninvasive evaluation of atherosclerotic plaques in both the thoracic and abdominal aortas. Plaques in the thoracic and abdominal aortas were found to be characteristically associated with hypercholesterolemia and smoking, respectively, suggesting different susceptibilities to risk factors. Because patients have various risk factors, it seems to be preferable to evaluate atherosclerosis in multiple vascular beds than in just 1 bed. Magnetic resonance imaging can evaluate atherosclerosis in multiple vascular beds in the same examination session. Complex aortic plaques, especially in the abdominal aorta, were found to be associated with myocardial infarction and complex coronary lesions, suggesting a link between aortic and coronary plaque instability. Aortic MRI may thus be useful for identifying vulnerable patients. Moreover, MRI is a powerful tool to serially evaluate plaque progression and regression. Intensive lipid-lowering therapy can regress aortic plaques, but the susceptibility to lipid lowering and the process of plaque regression may differ between the thoracic and abdominal aortic plaques.

Subclinical atherosclerosis in multiple vascular beds: an index of atherosclerotic burden evaluated in postmenopausal women

The Healthy Women Study has evaluated risk factor changes as women go through the menopause. In 274 women, measures of atherosclerosis in the coronary, aorta and carotid arteries were obtained at 8 years postmenopause using electron beam tomography and carotid ultrasound. The purpose of this study was to evaluate the association between baseline premenopausal risk factors and subclinical disease in various vascular beds and with an aggregate atherosclerosis index based on all subclinical measures. The prevalence of measurable disease for the coronaries, carotids and aorta was 45, 55 and 72%, respectively. Disease measures across these three locations were significantly correlated ( P<0.001). Premenopausal LDL, triglycerides, blood pressure (BP) and smoking were associated with each measure of subclinical atherosclerosis, and were strikingly associated with the number of elevated disease measures. Among 126 women taking hormone replacement therapy (HRT), there was a strong positive association between systolic BP and subclinical atherosclerosis ( P<0.001). No such relationship was seen among women not on HRT and this interaction was significant ( P=0.048). An index of subclinical atherosclerosis rather than measurement at a single arterial site may be the best estimate of disease risk. Such a measure should be evaluated for its prognostic value along with individual measures of subclinical disease. Women with lower premenopausal risk factors did not develop high levels of subclinical atherosclerosis, suggesting that atherosclerosis is a preventable disease in women.

Exercise and Postprandial Lipaemia

Postprandial hyperlipidaemia is a risk factor for atherosclerosis in multiple vascular beds, independently of high-density lipoprotein (HDL) cholesterol. An increased level of HDL cholesterol is a strong indicator of a low risk of atherosclerosis. Exercise decreases postprandial lipaemia and, in turn, increases levels of HDL cholesterol. The favourable effects of exercise on lipoprotein metabolism, particularly evident in the postprandial state, may thus help to decrease susceptibility to atherosclerosis in exercise-trained people.