Changes In Carotid Atherosclerosis Research Articles

Multi-Sequence MRI Registration of Atherosclerotic Carotid Arteries Based on Cross-Scale Siamese Network.

Cardiovascular disease (CVD) is a common disease with high mortality rate, and carotid atherosclerosis (CAS) is one of the leading causes of cardiovascular disease. Multisequence carotid MRI can not only identify carotid atherosclerotic plaque constituents with high sensitivity and specificity, but also obtain different morphological features, which can effectively help doctors improve the accuracy of diagnosis. However, it is difficult to evaluate the accurate evolution of local changes in carotid atherosclerosis in multi-sequence MRI due to the inconsistent parameters of different sequence images and the geometric space mismatch caused by the motion deviation of tissues and organs. To solve these problems, we propose a cross-scale multi-modal image registration method based on the Siamese U-Net. The network uses sub-networks with image inputs of different sizes to extract various features, and a special padding module is designed to make the network available for training on cross-scale features. In addition, to improve the registration performance, a multi-scale loss function under Gaussian smoothing is applied for optimization. For the experiments, we have collected a multi-sequence MRI image dataset from 11 patients with carotid atherosclerosis for a retrospective study. We evaluate our overall architectures by cross-validation on our carotid dataset. The experimental results show that our method can generate precise and reliable results with cross-scale multi-sequence inputs and the registration accuracy can be greatly improved by using the Gaussian smoothing loss function. The DSC of our Siamese structure can reach 84.1% on the carotid data set with cross-size input. With the use of GDSC loss, the average DSC can be improved by 5.23%, while the average distance between fixed landmarks and moving landmarks can be decreased by 6.46%.Our code is made publicly available at: https://github.com/MingHan98/Cross-scale-Siamese-Unet.

Deep Learning-Based Carotid Plaque Segmentation from B-Mode Ultrasound Images

Carotid ultrasound measurement of total plaque area (TPA) provides a method for quantifying carotid plaque burden and monitoring changes in carotid atherosclerosis in response to medical treatment. Plaque boundary segmentation is required to generate the TPA measurement; however, training of observers and manual delineation are time consuming. Thus, our objective was to develop an automated plaque segmentation method to generate TPA from longitudinal carotid ultrasound images. In this study, a deep learning-based method, modified U-Net, was used to train the segmentation model and generate TPA measurement. A total of 510 plaques from 144 patients were used in our study, where the Monte Carlo cross-validation was used by randomly splitting the data set into 2/3 and 1/3 for training and testing. Two observers were trained to manually delineate the 510 plaques separately, which were used as the ground-truth references. Two U-Net models (M1 and M2) were trained using the two different ground-truth data sets from the two observers to evaluate the accuracy, variability and sensitivity on the ground-truth data sets used for training our method. The results of the algorithm segmentations of the two models yielded strong agreement with the two manual segmentations with the Pearson correlation coefficient r = 0.989 (p < 0.0001) and r = 0.987 (p < 0.0001). Comparison of the U-Net and manual segmentations resulted in mean TPA differences of 0.05 ± 7.13 mm2 (95% confidence interval: 14.02–13.02 mm2) and 0.8 ± 8.7 mm2 (17.85–16.25 mm2) for the two models, which are small compared with the TPA range in our data set from 4.7 to 312.8 mm2. Furthermore, the mean time to segment a plaque was only 8.3 ± 3.1 ms. The presented deep learning-based method described has sufficient accuracy with a short computation time and exhibits high agreement between the algorithm and manual TPA measurements, suggesting that the method could be used to measure TPA and to monitor the progression and regression of carotid atherosclerosis.

A Voxel-Based Fully Convolution Network and Continuous Max-Flow for Carotid Vessel-Wall-Volume Segmentation From 3D Ultrasound Images.

Vessel-wall-volume (VWV) is an important three-dimensional ultrasound (3DUS) metric used in the assessment of carotid plaque burden and monitoring changes in carotid atherosclerosis in response to medical treatment. To generate the VWV measurement, we proposed an approach that combined a voxel-based fully convolution network (Voxel-FCN) and a continuous max-flow module to automatically segment the carotid media-adventitia (MAB) and lumen-intima boundaries (LIB) from 3DUS images. Voxel-FCN includes an encoder consisting of a general 3D CNN and a 3D pyramid pooling module to extract spatial and contextual information, and a decoder using a concatenating module with an attention mechanism to fuse multi-level features extracted by the encoder. A continuous max-flow algorithm is used to improve the coarse segmentation provided by the Voxel-FCN. Using 1007 3DUS images, our approach yielded a Dice-similarity-coefficient (DSC) of 93.2±3.0% for the MAB in the common carotid artery (CCA), and 91.9±5.0% in the bifurcation by comparing algorithm and expert manual segmentations. We achieved a DSC of 89.5±6.7% and 89.3±6.8% for the LIB in the CCA and the bifurcation respectively. The mean errors between the algorithm-and manually-generated VWVs were 0.2±51.2 mm3 for the CCA and -4.0±98.2 mm3 for the bifurcation. The algorithm segmentation accuracy was comparable to intra-observer manual segmentation but our approach required less than 1s, which will not alter the clinical work-flow as 10s is required to image one side of the neck. Therefore, we believe that the proposed method could be used clinically for generating VWV to monitor progression and regression of carotid plaques.

Fractal dimension based carotid plaque characterization from three-dimensional ultrasound images

Irregularity of the plaque surface associated with previous plaque rupture plays an important role in the risk estimation of stroke caused by carotid atherosclerotic lesions. Thus, the aim of this study is to develop and validate novel vulnerability biomarkers from three-dimensional ultrasound (3DUS) images by analyzing the surface morphological characteristics of carotid plaque using fractal geometry features. In the experiments, a total of 38 3DUS plaque images were obtained from two groups of patients treated with 80mg of atorvastatin or placebo daily for 3months respectively. Two types of 3D fractal dimensions (FDs) were used to describe the smoothness of plaque surface morphology and the roughness from intensity of 3DUS images. Student's t test showed that the two fractal features were effective for detecting the statin-related changes in carotid atherosclerosis with p < 0.00023 and p < 0.0113 respectively. It was concluded that the 3D FD measurements were effective for analyzing carotid plaque characteristics and especially effective for evaluating the impact of atorvastatin treatment. Graphical abstract ᅟ.

Relationship between frequency of hypoglycemic episodes and changes in carotid atherosclerosis in insulin-treated patients with type 2 diabetes mellitus

The effect of hypoglycemia on the progression of atherosclerosis in patients with type 2 diabetes mellitus (T2DM) remains largely unknown. This is a post hoc analysis of a randomized trial to investigate the relationship between hypoglycemic episodes and changes in carotid intima-media thickness (IMT). Among 274 study subjects, 104 patients experienced hypoglycemic episodes. Increases in the mean IMT and left maximum IMT of the common carotid arteries (CCA) were significantly greater in patients with hypoglycemia compared to those without hypoglycemia. Classification of the patients into three groups according to the frequency of hypoglycemic episodes showed that high frequency of hypoglycemic events was associated with increases in mean IMT-CCA, and left max-IMT-CCA and right max-IMT-CCA. In addition, repetitive episodes of hypoglycemia were associated with a reduction in the beneficial effects of sitagliptin on carotid IMT. Our data suggest that frequency of hypoglycemic episodes was associated with changes in carotid atherosclerosis.

Impact of Adapted Sports Activities on the Progression of Carotid Atherosclerosis in Subjects With Spinal Cord Injury

ObjectiveTo determine whether regular performance of adapted sports is associated with long-term changes in carotid atherosclerosis in subjects with spinal cord injury (SCI). DesignProspective observational study. SettingAcademic medical center. ParticipantsMen with chronic (>1y) SCI and no preserved motor function below the injury level were evaluated in 2007 and 2012 (N=17). Nine subjects did not perform physical activity between the studied time points (control group), whereas 8 subjects entered competitive upper-body sports programs (rugby: n=5, basketball: n=1, jiu-jitsu: n=1, and tennis: n=1) after baseline and were regularly training at the time of the second evaluation (sports group). InterventionsNot applicable. Main Outcome MeasuresClinical, laboratory, hemodynamic, and carotid ultrasonography analysis. ResultsThe studied groups showed no differences in all studied variables at baseline. After 5 years of follow-up, the control group showed increases in heart rate (87.0±3.1 vs 74.7±3.8 beats per minute; P=.004), but the participants had no significant changes in carotid intima-media thickness (IMT) (.65±.05 vs .67±.03mm; P=.73) or IMT/diameter (.118±.007 vs .136±.013; P=.24). In contrast, the sports group showed long-term decreases in carotid IMT (.56±.05 vs .74±.05mm; P=.001) and IMT/diameter (.097±.006 vs .141±.009; P<.001), but the participants did not show any variation in the other studied variables at follow-up. ConclusionsRegular upper-body sports activities are associated with long-term reductions in carotid atherosclerosis in subjects with SCI and might be a potential prevention strategy aiming to reduce cardiovascular risk in this population.

Prospective observation on the association of snoring with subclinical changes in carotid atherosclerosis over four years

ObjectiveAlthough there is a growing interest in the independent effect of snoring on carotid atherosclerosis, few studies have observed the relationship between snoring and change in carotid atherosclerosis prospectively. Therefore, the present study aimed to prospectively examine the association of snoring with subclinical changes in carotid atherosclerosis during a four-year period. MethodsParticipants in an ongoing prospective cohort study (n=3129) were enrolled. Subclinical changes in carotid atherosclerosis were assessed using: (i) mean and maximum intima-media thickness (IMT) on both common carotid arteries; (ii) prevalence of elevated IMT (maximum IMT ⩾1.0mm); and (iii) presence of plaque. Measurement was performed using B-mode ultrasonogram at baseline and after two and four years. Subjects were classified into three groups, based on self-reported snoring frequency at baseline: habitual, occasional, and non-snorer. ResultsAfter adjustment for conventional cardiovascular risk factors and self-reported witnessed sleep apnea, the present study found significant cross-sectional differences in mean and maximum IMT between female snorers and non-snorers at baseline only. The changes in IMTs and presence of plaque over four years, however, did not differ by three groups, with different snoring frequency in both genders. ConclusionsSnoring did not accelerate subclinical change in carotid atherosclerosis during a four-year follow-up, although baseline difference in IMT between snorers and non-snorers was significant in women, independent of witnessed sleep apnea. Additional longer-term studies with objective assessment of snoring are needed.

Two-Year Treatment with Rosuvastatin Reduces Carotid Intima-Media Thickness in HIV Type 1-Infected Patients Receiving Highly Active Antiretroviral Therapy with Asymptomatic Atherosclerosis and Moderate Cardiovascular Risk

Recent studies have shown that rosuvastatin significantly decreases serum levels of inflammatory biomarkers and slows progression of carotid atherosclerosis in the general population. However, there are no data about its effect on progression of atherosclerosis in HIV-infected patients. Adult patients with HIV infection, on stable antiretroviral therapy, with asymptomatic carotid atherosclerosis and hypercholesterolemia, who started a rosuvastatin treatment at 10 mg daily during the period 2007-2009 were enrolled and followed-up for 24 months. Thirty-six patients (30 males) were enrolled, with a mean age of 49 years, a mean duration of current antiretroviral therapy of 38 months, and a mean 10-year risk of myocardial infarction of 18.5%. Rosuvastatin led to a significant decrease in mean values of intima-media thickness in all extracranial carotid arteries, with the greatest magnitude observed in carotid bifurcations (a mean decrease of 18.7% in the right artery and of 21.4% in the left artery) and in internal carotid arteries (a mean decrease of 23.7% in the right artery and of 25.6% in the left artery). Moreover, there was a significant reduction in mean levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides versus respective baseline values associated with a significantly decreased mean cardiovascular risk. The treatment with rosuvastatin was well tolerated, and serious adverse events were not reported. A 24-month treatment with rosuvastatin in HIV-infected patients on highly active antiretroviral therapy (HAART) with subclinical atherosclerosis and a moderate cardiovascular risk seems to promote significantly favorable changes in carotid atherosclerosis, associated with a favorable effect on serum lipid levels and a good tolerability profile.

Texture analysis of carotid artery atherosclerosis from three-dimensional ultrasound images

To quantitatively evaluate local carotid arterial statin effects in 3D US images using multiclassifier image texture analysis tools. Texture analysis tools were used to evaluate the effect of 80 mg atorvastatin administered daily to patients with carotid stenosis compared to those treated with placebo. Using three-dimensional carotid ultrasound images, 270 texture features from seven texture techniques were extracted from manually segmented carotid arteries based on the intima-media boundary [vessel wall (VW)]. Individual texture features were compared to the previously determined changes in VW volume (VWV) using the distance between classes, the Wilcoxon rank sum test, and accuracy of the classifiers. Texture features that resulted in maximal classification accuracy from each texture technique were selected using Pudil's sequential floating forward selection (SFFS) as a method of ranking each technique. Finally, SFFS-selected texture features from all texture techniques were used in combination with 24 classifier fusion techniques to improve classification accuracy. Using the measurement of change in VWV, the distance between classes (DBC), Wilcoxon rank sum (WRS) p-value, and median accuracy measures (ACC) were 0.3798, 0.076, and 54.50%, respectively. Texture features improved the detection of statin-related changes using DBC to 0.5199, using WRS to 0.002, and ACC to 63.87%, respectively. The texture techniques that most differentiated between atorvastatin and placebo classes were Fourier power spectrum and Laws texture energy measures. The average classification accuracy between atorvastatin and placebo classes was improved from 57.22 +/- 12.11% using VWV to 97.87 +/- 3.93% using specific texture features. Furthermore, the use of specific texture features resulted in the average area under the receiver-operator characteristic curve (AUC) a value of 0.9988 +/- 0.0069 compared to 0.617 +/- 0.15 using carotid VWV. Based on DBC, WRS, ACC, and AUC texture features derived from 3D carotid ultrasound were observed to be more sensitive in detecting statin-related changes in carotid atherosclerosis than VWV suggesting that texture classifiers can be used to detect changes in carotid atherosclerosis after therapy.

Mapping Spatial and Temporal Changes in Carotid Atherosclerosis from Three-Dimensional Ultrasound Images

This study was designed to evaluate changes in carotid atherosclerosis using plaque and wall thickness maps derived from three-dimensional ultrasound (3DUS) images. Five subjects with carotid stenosis were scanned at baseline and 3 mo as part of a placebo-controlled intensive statin treatment study and three subjects with moderate atherosclerosis were scanned at baseline and again within 14 ± 2 d. 3DUS-derived vessel wall volume (VWV) was measured using manual segmentation to provide segmentation contours that were used to generate scan and rescan carotid atherosclerosis thickness maps and thickness difference maps. There was no significant difference in VWV between scan and rescan for the three subjects scanned twice in 2 wk or the single subject treated with placebo. There was a significant difference between scan and rescan VWV for carotid stenosis subjects treated with atorvastatin ( p < 0.001). Carotid atherosclerosis thickness difference maps showed visual qualitative evidence of thickness changes in vessel wall and plaque thickness in the common carotid artery for all statin-treated subjects and no change in a placebo-treated subject and subjects scanned twice in 2 wk. Carotid atherosclerosis thickness difference maps generated from 3DUS images provide evidence of vessel wall and plaque thickness changes for all subjects assessed. (E-mail: gep@imaging.robarts.ca)

Tracking regression and progression of atherosclerosis in human carotid arteries using high-resolution magnetic resonance imaging

Magnetic resonance imaging (MRI) can accurately and reproducibly measure the volume of atherosclerotic plaque in human carotid arteries. Atherosclerotic plaques may either progress or regress over time, depending on individual risk factors and treatment regimens. This study was designed to determine if regression or progression of human carotid atherosclerosis in patients receiving statin therapy over 24 months can be detected by high-resolution MRI. In 11 subjects who had undergone unilateral carotid endarterectomy and were on statin therapy, volumes for total carotid artery, concentric wall (normal wall), eccentric wall (plaque), and lumen were quantified at 0, 16 and 24 months using a 1.5-T human imager equipped with 6-cm phased array coils. The interobserver mean coefficient of variation (CV) was lowest for the lumen volume (3.1%) and highest for the plaque volume (9.8%). The interscan mean CV was lowest for the total artery volume (3.2%) and highest for the plaque volume (9.9%). As much as 26% regression and 35% progression were observed in individual subject's carotid artery eccentric wall (plaque) volumes over time. Mean eccentric wall volume increased 5% by 16 months and 8% by 24 months. Mean total wall volume increased slightly at both 16 and 24 months (+1.2% and +1.8%). High-resolution MRI provides a noninvasive reproducible method of tracking changes in carotid atherosclerosis. This pilot study detected changes in individual subjects at both 16 and 24 months. MRI tracking of changes in atherosclerotic plaques should prove useful in assessing vascular disease risk and monitoring the efficacy of interventions designed to induce regression or retard progression.

Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the Bruneck Study.

Susceptibility of the vasculature to the injurious effects of smoking varies substantially, with some smokers developing severe premature atherosclerosis and others remaining free of advanced atheroma until high ages. The present study sought to estimate the contribution of chronic infections to the variability of atherosclerosis severity among smokers. In the community-based Bruneck Study, 5-year changes in carotid atherosclerosis were assessed by high-resolution ultrasound. Early atherogenesis was defined by the development of nonstenotic plaques and advanced atherogenesis by the development/progression of vessel stenosis >40%. The risk of early atherogenesis strongly relied on lifetime smoking exposure and remained elevated long-term after cessation of smoking. Remarkably, current and ex-smokers faced an increased atherosclerosis risk only in the presence of chronic infections (odds ratios [95% CIs], 3.3 [1.8 to 6.2] and 3.4 [1.8 to 6.3]; P<0.001 each), whereas current, past, and nonsmokers without infections did not differ substantially in their estimated risk burden (odds ratios [95% CIs], 1.4 [0.8 to 2.4], 0.9 [0.6 to 1.6], and 1.0 [reference group]). In analogy to first-hand smoking, subjects exposed to environmental tobacco smoke were found to be vulnerable to the manifestation of chronic infection, and only those infected experienced a high atherosclerosis risk. The risk of advanced atherogenesis showed a dose-response relation with the number of daily cigarettes, returned to normal shortly after cessation of smoking, and emerged as independent of infectious illness. Our study provides the first epidemiological evidence that the proatherogenic effects of cigarette smoking are mediated in part by the chronic infections found in smokers. A better understanding of the vascular pathogenetic mechanisms of smoking may offer novel clues for disease prevention supplementary to the primary goal of achieving long-term abstinence.

Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study.

Chronic infections have been implicated in the pathogenesis of atherosclerosis, yet from an epidemiological perspective, this concept remains controversial. The Bruneck Study is a prospective population-based survey on the pathogenesis of atherosclerosis. In 826 men and women 40 to 79 years old (1990 baseline), 5-year changes in carotid atherosclerosis were thoroughly assessed by high-resolution duplex scanning. The presence of chronic respiratory, urinary tract, dental, and other infections was ascertained by standard diagnostic criteria. Chronic infections amplified the risk of atherosclerosis development in the carotid arteries. The association was most pronounced in subjects free of carotid atherosclerosis at baseline (age-/sex-adjusted odds ratio [95% CI] for any chronic infection versus none, 4.08 [2.42 to 6.85]; P:<0.0001) and applied to all types of chronic (bacterial) infections. It remained independently significant after adjustment for classic vascular risk attributes and extended to low-risk individuals free of conventional risk factors. Among subjects with chronic infections, atherosclerosis risk was highest in those with a prominent inflammatory response. Markers of systemic inflammation, such as soluble adhesion molecules and circulating bacterial endotoxin, and levels of soluble human heat-shock protein 60 and antibodies to mycobacterial heat-shock protein 65 were elevated in subjects with chronic infections and predictive of an increased risk of atherosclerosis. The present study provides solid evidence for a role of common chronic infections in human atherogenesis. Induction of systemic inflammation and autoimmunity may be potential pathophysiological links.

Impaired glucose tolerance, Type II diabetes mellitus and carotid atherosclerosis: prospective results from the Bruneck Study.

Cardiovascular disease is a well-known severe complication of impaired glucose tolerance and Type II (non-insulin-dependent) diabetes mellitus. The independent contribution of glucose intolerance to cardiovascular disease and the underlying pathogenic mechanisms are still, however, not clear. In this prospective population-based study, 826 subjects aged 40-79 years underwent high resolution duplex ultrasound examinations of carotid arteries and extensive clinical and laboratory screenings for potential vascular risk factors at baseline and 5 years later. The ultrasound protocol involved measurements of maximum axial diameter of atherosclerotic plaques, if any, in common and internal carotid arteries on both sides and enable differentiation of two main stages in carotid artery disease, termed early non-stenotic and advanced stenotic atherosclerosis. Intima-media thickness was assessed at the follow-up examination. Type II diabetes and, to a lesser extent, impaired glucose tolerance were found to be statistically significant risk predictors of 5-year changes in carotid atherosclerosis. These associations were in part independent of other vascular risk factors typically clustering with glucose intolerance. Both impaired glucose tolerance and Type II diabetes mellitus were not independently related to early non-stenotic atherosclerosis. In contrast, Type II diabetes mellitus was the strongest single risk predictor of advanced stenotic atherosclerosis [odds ratio 5.0 (95% confidence intervals 2.3-11.1)] and impaired glucose tolerance was of relevance as well [odds ratio 2.8 (1.2-6.4)] (p < 0.001). Impaired glucose tolerance and, to a greater extent, Type II diabetes were strong independent predictors of advanced carotid atherosclerosis in our prospective population-based study.

The natural course of atherosclerosis. Part I: incidence and progression.

The natural course of early atherogenesis is not well established. The current prospective survey was designed to monitor 5-year changes in carotid atherosclerosis in a large, stratified random sample of the general population using high-resolution duplex ultrasound (Bruneck Study). Incidence rates of carotid atherosclerosis ranged from near zero to 184 per 1000 person-years. Most atherosclerotic lesions developed at sites with enhanced wall thickness. Incidence of atherosclerosis in premenopausal women was less than half of that observed in men of equal age. The sex difference disappeared within 5 years after menopause and may possibly be attributed to sex variations in body iron stores. Preexisting atherosclerotic lesions may experience 1 of 2 different types of disease progression. 1) The first main type of plaque growth causing nonstenotic or diffuse dilative atherosclerosis was characterized by slow and continuous plaque extension, which usually affected several lesions simultaneously and did not primarily focus on the carotid bifurcation. This step-by-step process relied on a cumulative exposure to well-known risk factors such as hyper-lipidemia. Compensatory enlargement of the artery at the site of active atherosclerosis effectively preserved a (near) normal lumen. 2) The second main type of plaque growth was characterized by occasional prominent increases in lesion size. This process primarily occurred in the internal carotid artery and was mediated by procoagulant risk factors in a way that peak levels were relevant rather than cumulative exposure. As the main underlying pathomechanism, atherothrombosis may be hypothesized. Marked increases in plaque size and insufficient vascular remodeling acted synergistically in producing a significant compromise of the lumen. The current study provides novel insights into the natural course of early carotid atherosclerosis, thereby focusing on disease incidence and various types of spontaneous disease progression. Nonstenotic or diffuse dilating atherosclerosis and focal stenotic disease were found to constitute epidemiologically and etiologically distinct disease entities that develop and proceed independently of each other.

Alcohol Consumption and Atherosclerosis: What Is the Relation?

Potential effects of regular alcohol consumption on atherogenesis are still controversial mainly due to the lack of prospective population-based studies. The Bruneck Study is a prospective population-based survey of atherosclerosis and its risk factors. The study population comprises a sex- and age-stratified random sample of men and women aged 40 to 79 years. Participation and follow-up were more than 90% complete. Changes in carotid atherosclerosis between the 1990 baseline and the first follow-up in 1995 were monitored by high-resolution duplex ultrasonography. Alcohol intake was quantified with a standardized questionnaire and prospective diet records. Alcohol consumption less than once a week (occasional drinking) had no effect on atherogenesis. The association between regular alcohol intake and incident carotid atherosclerosis (early atherogenesis) was J-shaped, with light drinkers facing a lower risk than either heavy drinkers or abstainers. Protection offered by alcohol consumption of <50 g/d appeared to act through inhibition of the injurious action of high levels of low-density lipoprotein (LDL) cholesterol. Excess risk of incident atherosclerosis observed among heavy alcohol consumers (> or =100 g/d) clearly surpassed the risk burden afforded by heavy smoking. The association between regular alcohol intake and incident carotid stenosis (advanced atherogenesis) was U-shaped. Odds ratios were generally shifted toward protection and did not rely on LDL cholesterol levels. We failed to find any differential effects of alcohol from various sources. All associations remained independently significant when we adjusted for lifestyle, coincidental smoking, and the metabolic complex associated with drinking. Our findings support the view that adverse and beneficial effects of alcohol on arterial disease are mediated in part by a dose-dependent promotion or deceleration of atherogenesis. The protection afforded by light drinking may possibly be attributed to antithrombotic effects and inhibition of the atherogenic action of high levels of LDL cholesterol.