Role of the RNF213 Variant in Vascular Outcomes in Patients With Intracranial Atherosclerosis.

Background The RNF213 (ring finger protein 213 gene) variant R4810K is a susceptibility allele not only for Moyamoya disease (MMD) but also for intracranial atherosclerosis (ICAS) in East Asian populations. We hypothesized that this variant would affect the distribution of ICAS and recurrence of cerebrovascular events. Methods and Results We conducted a prospective study of patients with ICAS and MMD using high-resolution magnetic resonance imaging and RNF213 R4810K genotyping. Patients were included in the ICAS group when relevant plaques existed on high-resolution magnetic resonance imagingand in the MMD group when they carried the variant and high-resolution magnetic resonance imaging showed no plaques but characteristic features of MMD. We compared clinical and neuroimaging features of patients with ICAS-RNF213+ with patients with ICAS-RNF213- and of patients with MMD. Of 477 patients, 238 patients were in the ICAS group and 239 were in the MMD group. Among patients with ICAS, 79 patients (33.2%) were in the ICAS-RNF213+ group and 159 (66.8%) in the ICAS-RNF213- group. Tandem lesions were significantly more common in the ICAS-RNF213+ group than in the ICAS-RNF213- group (40.3% versus 72.2%, P<0.001), and their distributions were similar between the ICAS-RNF213+ and MMD groups. The presence of the R4810K variant (hazard ratio [HR], 3.203; 95% CI, 1.149-9.459; P=0.026) and tandem lesions (≥3) (HR, 8.315; 95% CI, 1.930-39.607; P=0.005) were independently associated with recurrent cerebrovascular events. Conclusions Patients with ICAS carrying the RNF213 R4810K variant showed clinical and imaging features distinct from patients with ICAS without the variant, suggesting that the R4810K variant plays a role in intracranial atherosclerosis in East Asian patients.

SNP rs2043211 (p.C10X) in CARD8 Is Associated with Large-Artery Atherosclerosis Stroke in a Chinese Population.

SNP rs2043211 in CARD8 was found to have significant association with ischemic stroke. This study aimed to explore the possible association between rs2043211 and large-artery atherosclerosis stroke in Chinese and explain the possible mechanism. In total, 716 large-artery atherosclerosis stroke patients and 1088 controls were included in the study. Co-dominant, dominant, and recessive genetic models were constructed to evaluate the relationship between rs2043211 and large-artery atherosclerosis stroke risk by odds ratios with 95% confidence intervals. Stratified and interaction analyses were also done. We selected another 111 large-artery atherosclerosis stroke patients and measured the CARD8 levels in their plasma samples by enzyme-linked immunosorbent assay. Participants who carry T/T genotype have a higher risk of large-artery atherosclerosis stroke compared with those carry A/T or A/A genotypes (odds ratio = 1.35, 95% confidence intervals 1.03-1.77, P = 0.029). The higher risk for the T/T genotype is still notable in female, people with hypertension, and people without diabetes. In the interaction analysis, compared to the non-hypertensive participants with the wild homozygote type A/A, the hypertensive participants with the A/T+T/T homozygote had 3.27-fold increased risk (odds ratio = 3.27, 95% confidence intervals 2.33-4.60). The A/A group had lower CARD8 levels in plasma than the A/T and T/T group (P < 0.001). Further bioinformatics prediction indicated that the rs2043211 could significantly influence the mRNA secondary structure and protein expression of CARD8 (eQTL P = 9.8 × 10-198). The rs2043211 is probably a novel biomarker for large-artery atherosclerosis stroke in Chinese.

Racial Differences in Prevalence and Risk for Intracranial Atherosclerosis in a US Community-Based Population.

Importance: Intracranial atherosclerotic disease (ICAD) is an important cause of stroke; however, little is known about racial differences in ICAD prevalence and its risk factors. Objective: To determine racial differences in ICAD prevalence and the risk factors (both midlife and concurrent) associated with its development in a large, US community-based cohort. Design, Setting, and Participants: Analysis of 1752 black and white participants recruited from the Atherosclerosis Risk in Communities (ARIC) cohort study who underwent 3-dimensional intracranial vessel wall magnetic resonance imaging from October 18, 2011 to December 30, 2013; data analysis was performed from October 18, 2011 to May 13, 2015. Exposures: Midlife and concurrent cardiovascular risk factors. Main Outcomes and Measures: Intracranial plaque presence, size (maximum normalized wall index) and number were assessed by vessel wall magnetic resonance imaging. Midlife and concurrent vascular risk factor associations were determined by Poisson regression (plaque presence), negative binominal regression (plaque number), and linear regression (plaque size), and compared between races. Results: Of the 1752 study participants (mean [SD] age, 77.6 [5.3] years; range, 67-90 years), 1023 (58.4%) were women and 518 (29.6%) were black. Black men had the highest prevalence (50.9% vs 35.9% for black women, 35.5% for white men, and 30.2% for white women; P < .001) and the highest frequency (22.4% vs 12.1% for black women, 10.7% for white men, and 8.7% for white women; P < .01) of multiple plaques. Prevalence increased with age, reaching 50% before ages 68, 84, and 88 years in black men, white men, and white women, respectively (ICAD prevalence remained <50% in black women). Midlife hypertension and hyperlipidemia were associated with 29% (prevalence ratio [PR], 1.29; 95% CI, 1.08-1.55) and 18% (PR, 1.18; 95% CI, 0.98-1.42), respectively, increased ICAD prevalence with no significant differences between races. Midlife hypertension was also associated with larger plaques (1.11 higher mean maximum normalized wall index; 95% CI, 0.21-2.01). Midlife smoking and diabetes were associated with increased risk of ICAD in black individuals (102% [PR, 2.02; 95% CI, 1.12-3.63] and 57% [PR, 1.57; 95% CI, 1.13- 2.19], respectively), but not in white participants (P < .05 interaction by race). Conclusions and Relevance: The prevalence of ICAD was highest in black men. Midlife smoking and diabetes were strongly associated with late-life ICAD in blacks only, whereas midlife hypertension and hyperlipidemia were associated with late-life ICAD in both races. These associations may help to explain racial differences in US stroke rates and offer insight into preventive risk-factor management strategies.

Correlation of Plasma Vascular Endothelial Growth Factor and Endostatin Levels with Symptomatic Intra- and Extracranial Atherosclerotic Stenosis in a Chinese Han Population.

BACKGROUND: Symptomatic intracranial atherosclerotic stenosis (ICAS) and extracranial atherosclerotic stenosis (ECAS) are different in many aspects. Here, we explored the association between the location or severity of atherosclerotic stenosis and pro- or antiangiogenic factors, specifically vascular endothelial growth factor (VEGF) and endostatin (ES). METHODS: We evaluated 198 consecutive patients with acute ischemia stroke: 132 with large-artery atherosclerosis (LAA) and 66 with small-artery occlusion (small-vessel occlusion). The LAA group was subclassified into 102 patients with ICAS and 30 with ECAS. Independent associations of VEGF, ES levels, and VEGF/ES ratio with the location of cerebral stenosis and the severity or short-term prognosis (14th day modified Rankin Scale) of ICAS were evaluated. RESULTS: Plasma concentrations of VEGF and ES were lower (P < .05) in ICAS (38.07, 32.76-46.28 pg/mL and 58.95, 55.04-59.77 ng/mL) than those in ECAS (45.00, 34.30-83.34 pg/mL and 140.74, 85.63-231.21 ng/mL). Logistic regression analysis showed that VEGF concentrations and dyslipidemia were independently associated with ICAS, with odds ratios of .987 [95% CI = (.976, .998)] and .265 [95% CI = (.103, .792)], respectively. Moreover, plasmatic VEGF levels increased gradually along with the severity of ICAS (P = .003), and lower levels of ES (P = .040) or a higher VEGF/ES ratio (P = .048) were related to unfavorable short-term prognosis of ICAS. CONCLUSION: Lower VEGF levels are associated with the presence of symptomatic ICAS, but not with ECAS. Furthermore, the severity of ICAS is positively correlated with the levels of VEGF, and lower ES levels or a predominance of VEGF over ES are predictors of poor short-term prognosis of ICAS.

Smoking and white matter hyperintensity progression: the ARIC-MRI Study.

OBJECTIVE: Our objective was to examine the link between smoking and smoking history, including smoking intensity and cessation, overall and by race, in a biracial prospective cohort study. METHODS: A subset of Atherosclerosis Risk in Communities Study participants (n = 972, 49% black) completed brain MRI scans twice (1993-1995 and 2004-2006). We defined white matter hyperintensity (WMH) progression as an increase of ≥2 points on the 9-point Cardiovascular Health Study scale across scans. Participants reported information on smoking behavior at the baseline MRI and at 2 prior study visits, approximately 3 and 6 years before baseline. We used adjusted logistic regression to evaluate the association between smoking variables and WMH progression in the total sample and separately by race (black and white). RESULTS: We found WMH progression in 23% of participants (30% of black participants, 17% of white participants). Overall, being a current smoker 6 years before baseline was associated with WMH progression. In race-stratified analyses, we found adverse associations with smoking status at multiple time points and persistent smoking in white but not in black participants. However, we found no statistical support for effect modification by race for most of these analyses. Increasing pack-years of smoking was associated with greater risk of WMH progression, while time since quitting and age at smoking initiation were not associated with WMH progression, with little indication of differences in these associations by race. CONCLUSIONS: Our findings concur with previous studies suggesting a relationship between smoking and WMH progression, and further demonstrate a dose-dependent association.

Synergistic effect of ALOX5AP polymorphisms and cigarette smoking on the risk of atherosclerotic cerebral infarction in a Northern Han Chinese population.

The effect of activating 5-lipoxygenase (ALOX5AP) gene polymorphisms on stroke risk may be influenced by the coexistence of modifiable predisposing conditions. We explored the interactions of ALOX5AP polymorphisms and cigarette smoking in a case-control study of patients with atherosclerotic cerebral infarction (ACI). Three polymorphisms of the ALOX5AP gene (rs10507391, rs4769874, and rs9551963) were analyzed in 420 ACI patients and 488 unrelated healthy controls matched for age and sex from a Northern Han Chinese population. Among the three single nucleotide polymorphisms, only rs10507391 genotype TT/TA was observed to be associated with an increased risk of ACI on multivariate analysis (odds ratio [OR]=1.82, 95% confidence interval [CI]=1.14-2.92, p=0.012) compared with the AA genotype. However, after stratifying by smoking status, multivariate logistic regression analysis revealed that rs10507391 genotype TT/TA and rs9551963 genotype CC/CA had a 5.63-fold (OR=5.63, 95%CI=2.00-15.84, p=0.001) and a 2.71-fold (OR=2.71, 95%CI=1.28-5.73, p=0.009) increased risk for ACI patients who smoked compared with the AA genotype, respectively. Additionally, according to the haplotype analysis, the risk of haplotype TGC (OR=3.12, 95%CI=2.00-4.88, p<0.001, corrected p [pc]<0.001) increased for ACI patients who smoked compared to the data (OR=1.60, 95%CI=1.28-1.98, p<0.001, pc<0.001) in total samples. These results suggest that ALOX5AP polymorphisms are associated with ACI, and cigarette smoking along with ALOX5AP could increase the risk of ACI.

Geographic and sex difference in the distribution of intracranial atherosclerosis in China.

BACKGROUND AND PURPOSE: Geographic variation and sex difference in the distribution of intracranial atherosclerosis (ICAS) have not been fully discussed before in Chinese patients with cerebral ischemia. We performed this study with the aim to investigate geographic and sex difference in the distribution of ICAS in China. METHODS: In this prospective multicenter study, we evaluated 2864 consecutive patients who experienced an acute cerebral ischemia within 7 days of symptom onset in 22 hospitals in China. All the inclusive patients underwent 3-dimensional time-of-flight MR angiography and duplex color Doppler ultrasound or contrast-enhanced MR angiography to document the presence of intracranial or extracranial stenosis. Intracranial large-artery atherosclerosis was defined as ≥50% diameter reduction on MR angiography. RESULTS: The proportion of patients with ICAS was significantly higher in north China than in south China (50.22% versus 41.88%; P<0.0001). Patients in the north were likely to consume more alcohol and smoke more cigarettes and had significantly higher proportion of diabetes mellitus, family history of stroke, history of cerebral ischemia, heart disease, and higher body mass index. In patients aged >63 years, the percentage of ICAS in women was notably higher than in men (51.51% versus 45.40%; P=0.028). In elderly patients, women had higher proportion of diabetes mellitus, hypertension, hyperlipidemia, and heart disease than men. CONCLUSIONS: There exists geographic and sex difference in the distribution of symptomatic ICAS in China. Public health measures should strengthen improving social determinants of health and risk factor prevention/control in high-risk populations for decreasing stroke risk.

Impact of metabolic syndrome on distribution of cervicocephalic atherosclerosis: data from a diverse race-ethnic group.

BACKGROUND: Vascular localization of symptomatic large artery atherosclerotic (LAA) stroke differs for unknown reasons by race-ethnicity. The metabolic syndrome (MetSD) is associated with higher atherosclerotic stroke risk and comprises abnormal risk factors that can vary by race. Thus, we investigated whether MetSD may contribute to race-ethnic differences in LAA stroke by examining the association of MetSD with symptomatic intra- and extracranial atherosclerosis among a diverse race-ethnic group. METHOD: We analyzed data prospectively collected over a 4-year period on subjects with ischemic stroke/TIA. Independent vascular risk factor associations with intracranial and extracranial LAA vs. non-LAA mechanism were evaluated in two groups stratified by race-ethnicity; whites and non-whites (Hispanics, African-American, and Asian-American). RESULTS: 1167 patients met study criteria. Intracranial LAA was more prevalent in non-whites vs. whites (20.4% vs. 9.6%, P<0.001), while extracranial LAA had a more frequent point value in whites compared to non-whites (10.7% vs. 7.5%, P=0.267). The presence of MetSD was more prevalent in both intracranial and extracranial LAA group than in non-LAA group: no significant differences were observed in the prevalence of MetSD between intra vs. extracranial LAA or whites vs. non-whites. However, with increasing numbers of abnormal metabolic components, whites were more likely to have experienced extracranial LAA, whereas non-whites were more likely to have experienced intracranial LAA. After adjusting for covariates, MetSD was associated with extracranial LAA in whites (OR, 1.98; 95% CI, 1.13-3.45), while there was a tendency that intracranial LAA was associated with MetSD in non-whites (OR, 1.80; 95% CI, 0.97-3.32). No association was found between MetSD and extracranial LAA in non-whites and between this syndrome with intracranial LAA in whites. CONCLUSIONS: Our results showed that the impact of MetSD on the distribution of cervicocephalic atherosclerosis differed by race-ethnicity. This finding may in part explain the well-known differences in race-ethnic predilection to intracranial or extracranial atherosclerosis.

Computed tomography evaluation of intracranial atherosclerosis in Chinese patients with transient ischemic attack or minor ischemic stroke--its distribution and association with vascular risk factors.

OBJECTIVES: Intracranial atherosclerosis has been suggested to be common in Asians. We apply a semi-quantitative CT scoring system to evaluate the degree of intracranial atherosclerotic calcification and determine its distribution, severity, and the associated risk factors. The clinical outcome of these patients after a 3-year follow-up was also evaluated. METHODS: Sixty consecutive patients diagnosed clinically to have either a transient ischemic attack (TIA) or minor ischemic stroke and underwent early computed tomographic angiography (CTA) were included into the prospective study. Two radiologists evaluated the axial CTA images for any calcification in the precavernous, cavernous and postcavernous segments of intracranial internal carotid artery (ICA), anterior, middle, and posterior cerebral as well as vertebrobasilar arteries, based on a standard CT scoring system for extent (0-4) and thickness (0-4). The composite CT score for extent and thickness of these vascular segments or vessels were recorded for all patients. The worst site (highest composite score) was chosen as the marker of the degree of intracranial atherosclerosis of each patient. The patients were then classified into mild, moderate, and severe groups, according to a composite CT score of 0-2, 3-5, and 6-8, respectively. These findings were gathered with clinical parameters and outcome after a 3-year follow-up period and corresponding statistical analyses were conducted. RESULTS: The most severely affected vessel was found to be intracranial internal carotid arteries, and severe, moderate, and mild atherosclerosis were present in 16 (26.67%), 30 (50%), and 14 (23.33%) patients, respectively. Using multiple logistic regression analysis, diabetes mellitus (odds ratio = 10.6, P value = .004), and age (odds ratio = 1.07, P value = .02) were found to be significant risk factors for severe intracranial atherosclerosis. Two patients in the severe group, 3 patients in the moderate group, and 1 patient in the mild group were found to have stroke or TIA after a 3-year follow-up, but there was no significant difference among the 3 groups. CONCLUSION: Significant intracranial atherosclerosis as determined by severe CT calcification was common in a cohort of Chinese patients with TIA and minor stroke. Age and diabetes mellitus were independent significant risk factors, and this CT calcification score might serve as an early indicator of intracranial atherosclerotic disease.

Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome.

Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction. Among these polymorphisms, the 2445G-->A (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.

Echocardiographic left ventricular mass index predicts incident stroke in African Americans: Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND AND PURPOSE: Despite theories that link stroke to left ventricular mass, few large, population-based studies have examined the predictive value of echocardiographically derived left ventricular mass index (LVMI) to incident stroke in African Americans. METHODS: Participants in the Jackson cohort of the Atherosclerotic Risk in Communities study have had extensive baseline evaluations, have undergone echocardiography during the third examination (1993-1995), and have been followed up for incident cardiovascular disease including ischemic stroke. RESULTS: The study population consisted of 1792 participants, of whom 639 (35.7%) were men and the mean+/-SD age was 58.8+/-5.7 years. Compared with those without ischemic stroke, those with ischemic stroke had a higher frequency of hypertension (85.6% vs 58.7%) and diabetes (46.9% vs 21.0%). Left ventricular hypertrophy was more prevalent in those with stroke (62.2% vs 38.6%). During a median follow-up of 8.8 years, 98 incident strokes occurred (6.5 per 1000 person-years). LVMI was independently associated with stroke after adjusting for age, sex, hypertension, systolic blood pressure, smoking, diabetes, total to HDL cholesterol ratio, body mass index, and low left ventricular ejection fraction (adjusted hazard ratio per 10 g/m(2.7) increment of LVMI=1.15; 95% CI, 1.02 to 1.28). The relation remained statistically significant after adding left atrial size and mitral annular calcification to the multivariable model. CONCLUSIONS: In this large, population-based African American cohort, we found that echocardiographic LVMI was an independent predictor of incident ischemic stroke even after taking into account traditional clinical risk factors.

Risk factors for new atherothrombotic brain infarction in older African-American men and women.

Independent risk factors for new atherothrombotic brain infarction (ABI) in older African-American men were hypertension (risk ratio 4.381), diabetes mellitus (risk ratio 2.872), and previous ABI (risk ratio 1.904). Independent risk factors for new coronary events in older African-American women were cigarette smoking (risk ratio 2.754), hypertension (risk ratio 5.914), diabetes mellitus (risk ratio 3.464), serum total cholesterol (risk ratio 1.008), serum high-density lipoprotein cholesterol (inverse association) (risk ratio 0.958), age (risk ratio 1.026), and previous ABI (risk ratio 2.601).

Prevalence of coronary artery disease, atherothrombotic brain infarction, and peripheral arterial disease: associated risk factors in older Hispanics in an academic hospital-based geriatrics practice.

OBJECTIVE: To investigate the prevalence of coronary artery disease (CAD), atherothrombotic brain infarction (ABI), and peripheral arterial disease (PAD) in older Hispanics and the association with risk factors in this population. DESIGN: A retrospective analysis of charts from all Hispanics seen during January 1996 through July 1997 at an academic hospital-based geriatrics practice. SETTING: An academic, hospital-based, primary care geriatrics practice staffed by fellows in a geriatrics training program and by full-time faculty geriatricians. PATIENTS: One hundred sixty women and 53 men, mean age 80 +/- 8 years (range 64 to 100), were included in the study. MEASUREMENTS AND MAIN RESULTS: Of 213 Hispanics in the study, 59 (28%) had documented CAD, 43 (20%) had ABI, 34 (16%) had PAD, and 90 (42%) had either CAD, ABI, or PAD. Serum total cholesterol and triglycerides were measured in 202 of 213 subjects (95%). Serum high-density lipoprotein cholesterol was measured in 137 of 213 patients (64%). Other risk factor data were documented in all patients. Multiple logistic regression analysis performed in 202 patients using the variables age, gender, cigarette smoking, hypertension, diabetes mellitus, obesity, serum total cholesterol, and serum triglycerides showed statistically significant associations between prevalent CAD, ABI, or PAD and age (P = .002, odds ratio (OR) = 1.083), cigarette smoking (P = .002, (OR) = 3.865), hypertension (P = .007, (OR) = 2.749), diabetes mellitus (P = .028, (OR) = 2.386), obesity (P = .014, (OR) = 2.608), serum total cholesterol (P < 0.001, (OR) = 1.025), and serum triglycerides (P = .017, (OR) = .993). CONCLUSIONS: Either CAD, ABI, or PAD was present in 42% of 213 older Hispanics. There were statistically significant associations between prevalent CAD, ABI, or PAD in older Hispanics and risk factors, including age, cigarette smoking, hypertension, diabetes mellitus, obesity, and serum total cholesterol.

Pathology of cerebral atherosclerosis. Influence of age, race, and gender.

Age, race, and gender are among the logical variables to investigate in determining the natural history of disease. In this connection, the pathological lesions of cerebral atherosclerosis have been particularly difficult to investigate. The limitations of autopsy populations, time-consuming dissections of the intracranial and extracranial arteries, and numerous technical problems associated with specimen preparation, shipment, and storage are among the impediments. Long-term repeated studies and grading systems, and the validation thereof, are also elements adding to the complexity of these studies. In the currently available publications, the most systematic studies, several of which are international in scope and from diverse medical centers, permit some tentative conclusions: (1) There is no reliable evidence of a qualitative difference in the lesions of cerebral atherosclerosis among diverse autopsy populations. (2) Quantitative differences exist in lesion severity among different age groups and races and between males and females. (3) Quantitative differences in intracranial versus extracranial atherosclerosis exist that are related to age and to race (white versus black versus Asian) and gender. (4) The role of hypertension as a factor leading to more severe and more complicated lesions is most obvious in black and Japanese autopsy populations, but its influence is not a simple one to decipher. Complicated lesions refer to stenosis, ectasias and aneurysms, thrombosis, ulceration, and calcification and hemorrhages in plaques. (5) Diet is one obvious variable differing in the populations studied so far. Cigarette smoking is probably an important factor in several populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Progression of carotid atherosclerosis in Japanese patients with coronary artery disease.

BACKGROUND AND PURPOSE: Along with the recent changes in lifestyle in Japan, the incidence of coronary artery disease has increased while the incidence of stroke appears to be decreasing. We investigated the relation between the progression of carotid atherosclerosis and the severity of coronary artery disease in the Japanese population. METHODS: The 2-year change in extracranial carotid atherosclerosis in 50 Japanese patients who underwent coronary angiography was evaluated using carotid echotomography. To quantify the extent of carotid atherosclerosis, the maximal thickness measurements of all plaques were summed for an individual plaque score, except for new plaques found on reexamination. Carotid disease progression was evaluated by the sum of plaque score change and the thickness of the new plaque found on reexamination. RESULTS: The plaque score changed by -3.2 to 10.1 mm (mean +/- SD, 1.06 +/- 2.42 mm). The extent of coronary atherosclerosis (p less than 0.02) and serum total cholesterol level (p less than 0.01) were different between the progressing (n = 17) and the nonprogressing (n = 30) groups of carotid atherosclerosis when the progressing group included the patients with a delta plaque score of greater than or equal to 1.0 mm. Neither age, serum triglyceride level, serum high-density lipoprotein cholesterol level, pack-years of smoking, percentage of smokers, percentage of hypertensive patients, nor percentage of diabetic patients was different between the two groups. Carotid disease progression was significantly higher in patients with three-vessel coronary disease than in patients without significant coronary artery disease (p less than 0.005). There was a significant positive linear correlation between carotid disease progression and Gensini's coronary artery disease score (R = 0.411, p less than 0.005). CONCLUSIONS: Our data showed that severe coronary artery disease and a high serum total cholesterol level were strong predictors for carotid disease progression in Japanese patients with high rates of coronary artery disease.