Prevalence of vertebral artery origin stenosis and occlusion in outpatient extracranial ultrasonography.

BACKGROUND AND PURPOSE: Most data on the prevalence of vertebral artery origin (VAo) disease is derived from hospital-based studies of patients with posterior circulation strokes and TIA. The prevalence of VAo disease in patients without posterior circulation symptoms or asymptomatic patients is poorly characterized. Our objective was to examine the prevalence of VAo stenosis and occlusion in consecutive patients, presenting for extracranial ultrasonography to an outpatient laboratory. METHODS: We retrospectively identified 2490 consecutive extracranial duplex studies performed in an ambulatory neurovascular ultrasound laboratory. All studies were reviewed for the presence of >50% VAo stenosis, defined as a PSV > 114 cm/s, and VA occlusion. We also reviewed the prevalence of >50% carotid stenosis, defined as a PSV > 120 cm/s, in the same population, to draw comparisons with VAo stenosis prevalence. RESULTS: We identified right VAo stenosis in 52/1955 (2.7%) and occlusion in 74/1955 (3.9%) and left-sided VAo stenosis in 45/1973 (2.5%) and occlusion in 64/1973 (3.6%). The prevalence of having any (either right or left) VAo stenosis or occlusion was 8.2% and 1.4% had bilateral VAo stenosis or occlusion. Right carotid stenosis and occlusion was found in 236/2399 (9.8%) and 53/2399 (2.2%) and left carotid stenosis and occlusion in 236/2397 (9.8%) and 45/2397 (1.9%), respectively. Any carotid disease, either right or left, was present in 18.9% and 4.7% had bilateral carotid disease. CONCLUSION: Although less prevalent than cervical carotid disease, we found that approximately 8% of patients who presented to an ambulatory ultrasound laboratory had >50% VAo disease.

Prevalence of vertebral artery origin stenosis and occlusion in outpatient extracranial ultrasonography.

BACKGROUND AND PURPOSE: Vertebral artery origin stenosis prevalence. Most data on the prevalence of vertebral artery origin (VAo) disease is derived from hospital-based studies of patients with posterior circulation strokes and TIA. The prevalence of VAo disease in patients without posterior circulation symptoms or asymptomatic patients is poorly characterized. Our objective was to examine the prevalence of VAo stenosis and occlusion in consecutive patients, presenting for extracranial ultrasonography at an outpatient laboratory. METHODS: We retrospectively identified 2490 consecutive extracranial duplex studies performed in an ambulatory neurovascular ultrasound laboratory. All studies were reviewed for the presence of >50% VAo stenosis, defined as a PSV > 114 cm/s, and VA occlusion. We also reviewed the prevalence of >50% carotid stenosis, defined as a PSV > 120 cm/s, in the same population, to draw comparisons with VAo stenosis prevalence. RESULTS: We identified right VAo stenosis in 52/1955 (2.7%) and occlusion in 74/ 1955 (3.9%) and left-sided VAo stenosis in 45/1973 (2.5%) and occlusion in 64/1973 (3.6%). The prevalence of having any (either right or left) VAo stenosis or occlusion was 8.2% and 1.4% had bilateral VAo stenosis or occlusion. Right carotid stenosis and occlusion was found in 236/2399 (9.8%) and 53/2399 (2.2%), and left carotid stenosis and occlusion in 236/2397 (9.8%) and 45/2397 (1.9%), respectively. Any carotid disease, either right or left, was present in 18.9% and 4.7% had bilateral carotid disease. CONCLUSION: Although less prevalent than cervical carotid disease, we found that approximately 8% of patients who reported to an ambulatory ultrasound laboratory had >50% VAo disease.

Racial-ethnic differences in lacunar infarction in a multiethnic stroke population.

A higher incidence of lacunar infarction (LI) has been reported in nonwhite stroke populations. This study examined racial-ethnic differences in the clinical presentation and imaging findings of a racially-ethnically diverse population with acute LIs. Patients with acute LIs were identified over a 3-year period. Baseline clinical characteristics, vascular risk factors, and magnetic resonance imaging findings were analyzed. Comparisons were made between African Americans, Caribbean blacks, Caribbean Hispanics, and non-Hispanic whites. During the study period, 1036 patients with ischemic stroke were admitted, 194 of whom (25%) had a LI. The proportion of LI was the highest in Caribbean blacks (40%) and lowest in non-Hispanic whites (7%), with African Americans (25%) and Caribbean Hispanics (22%) showing a similar frequency. The mean patient age was 62 ± 12 years, and the study group was 55% male. Hypertension (92%) and dyslipidemia (74%) were the most frequent risk factors. The prevalence of hypertension was highest in African Americans and Caribbean blacks, whereas Caribbean Hispanics were more likely to smoke and have dyslipidemia. Despite similar vascular risk factors and a shared genealogy, the proportion of LI differed in African Americans and Caribbean blacks. Conversely, no difference in the prevalence of LI was seen in African Americans and Caribbean Hispanics, even though the 2 groups had differences in vascular risk factors. Our findings suggest that other determinants besides traditional vascular risk factors influence the risk of LI.

Association between variations in coagulation system genes and carotid plaque.

OBJECTIVE: Genetic variation in coagulation and fibrinolysis may affect the development of subclinical atherosclerosis modifying the risk of stroke and cardiovascular disease. However, data on the relationship between subclinical atherosclerosis and genes involved in the coagulation system are sparse. The objective of this study is to examine the association between single nucleotide polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque phenotypes. METHODS: From the Genetic Determinants of Subclinical Carotid Disease Study, 287 Dominicans were examined for carotid plaque presence, thickness, and surface irregularity by high-resolution B-mode carotid ultrasound. Logistic regression was used to test for association between 101 SNPs in 23 coagulation system genes and plaque phenotypes while controlling for age, sex, smoking, hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions between genes were examined. A follow-up of SNPs in moderate to high (r(2)>0.25) linkage disequilibrium (LD) with those implicated in the discovery analysis (p ≤ 0.01) was performed in an independent sample of 301 Dominicans. RESULTS: The prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean age (65 ± 8 discovery; 65 ± 9 follow-up) of the participants was similar in both datasets. Two genes (vWF and THBS1) were associated (p ≤ 0.01) with plaque size and surface irregularity. In follow-up, 5 SNPs in vWF were associated (p ≤ 0.05) with plaque size. SERPINE1 was an additional gene of interest in the haplotype and interaction analyses. CONCLUSIONS: Variation in the vWF, THBS1, and SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic plaque.

Association of the sirtuin and mitochondrial uncoupling protein genes with carotid plaque.

OBJECTIVE: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in cardiovascular diseases through the control of reactive oxygen species production. This study sought to investigate the association between genetic variants in the SIRT and UCP genes and carotid plaque. METHODS: In a group of 1018 stroke-free subjects from the Northern Manhattan Study with high-definition carotid ultrasonography and genotyping, we investigated the associations of 85 single nucleotide polymorphisms (SNPs) in the 11 SIRT and UCP genes with the presence and number of carotid plaques, and evaluated interactions of SNPs with sex, smoking, diabetes and hypertension as well as interactions between SNPs significantly associated with carotid plaque. RESULTS: Overall, 60% of subjects had carotid plaques. After adjustment for demographic and vascular risk factors, T-carriers of the SIRT6 SNP rs107251 had an increased risk for carotid plaque (odds ratio, OR = 1.71, 95% CI = 1.23-2.37, Bonferroni-corrected p = 0.03) and for a number of plaques (rate ratio, RR = 1.31, 1.18-1.45, Bonferroni-corrected p = 1.4×10(-5)), whereas T-carriers of the UCP5 SNP rs5977238 had an decreased risk for carotid plaque (OR = 0.49, 95% CI = 0.32-0.74, Bonferroni-corrected p = 0.02) and plaque number (RR = 0.64, 95% CI = 0.52-0.78, Bonferroni-corrected p = 4.9×10(-4)). Some interactions with a nominal p≤0.01 were found between sex and SNPs in the UCP1 and UCP3 gene; between smoking, diabetes, hypertension and SNPs in UCP5 and SIRT5; and between SNPs in the UCP5 gene and the UCP1, SIRT1, SIRT3, SIRT5, and SIRT6 genes in association with plaque phenotypes. CONCLUSION: We observed significant associations between genetic variants in the SIRT6 and UCP5 genes and atherosclerotic plaque. We also found potential effect modifications by sex, smoking and vascular risk factors of the SIRT/UCP genes in the associations with atherosclerotic plaque. Further studies are needed to validate our observations.

Short-term effect of atorvastatin on carotid artery elasticity: a pilot study.

BACKGROUND AND PURPOSE: Few studies have examined the early effects of statins on carotid artery elasticity, a potential surrogate marker of cardiovascular risk. This study examined the short-term effects of atorvastatin 80 mg daily on carotid elasticity measured by high-resolution B-mode ultrasound. METHODS: The study included 40 stroke-free and statin-naive subjects older than age 45 (mean age, 70±7 years; 55% men; 64% Caribbean-Hispanic). Outcome measures included carotid stiffness indices at 14 and 30 days after initiation of treatment. The systolic and diastolic diameters of the right common carotid artery were averaged from multiple B-mode imaging frames. Absolute and relative changes of strain [(systolic diameter-diastolic diameter)/diastolic diameter], stiffness (ß) [ln (systolic/diastolic blood pressure)/strain], and distensibility (1/ß adjusted for wall thickness) from baseline were compared by the repeated measures t test and were considered significant at α=0.05. RESULTS: Baseline mean stiffness was 0.08 (95% confidence interval [CI], 0.06-0.10). It significantly decreased at day 30 to 0.05 (CI, 0.04-0.06; P<0.01). Mean baseline distensibility was 15.25 (CI, 13.18-17.32), increasing significantly at day 30 to 17.23 (CI, 14.01-20.45; P<0.05). An improvement in distensibility of ≥10% from baseline was observed in 29 (73%) subjects. Changes in stiffness and distensibility were maximal among subjects with baseline low-density lipoprotein levels<130 mg/dL. CONCLUSIONS: Short-term treatment with high-dose atorvastatin was associated with improvement in the carotid elasticity metrics. Carotid artery elasticity measured by B-mode ultrasound is a simple noninvasive measure of arterial wall function and may be a useful surrogate end point in clinical trials targeting individuals at increased risk for atherosclerosis.

Imaging evolution of acute lacunar infarction: leukoariosis or lacune?

BACKGROUND: In acute lacunar infarction, MRI may overestimate eventual infarct size and the imaging evolution of acute lesions is not fully understood. Our objective was to examine eventual infarct size, the incidence of cavity formation, and factors associated with cavitation in patients presenting with acute lacunar infarction. METHODS: Patients with acute diffusion-weighted imaging (DWI) infarcts ≤25 mm in diameter, in the distribution of a penetrating artery, who had a follow-up MRI or CT at least 1 month or longer from stroke onset were retrospectively included. We measured baseline lesion size on DWI and T2/fluid-attenuated inversion recovery (FLAIR) and follow-up lesion size on T2/FLAIR and CT. Follow-up MRI and CT images were assessed for cavity formation. Predictors for cavitation were assessed in a multivariate model. RESULTS: We identified 75 patients with lacunar infarction and follow-up CT or MRI, done 20.2 ± 16.6 and 21.2 ± 17.4 months after stroke, respectively. Mean baseline DWI size was 13.5 ± 5.7 and T2/FLAIR size was 13.1 ± 5.3 mm. Follow-up T2/FLAIR lesion size was 8.2 ± 3.4 mm and smaller than baseline DWI and T2/FLAIR (p = <0.001). Follow-up whole lesion size on CT scan was 7.1 ± 4.1 and smaller than baseline DWI and T2/FLAIR (p = 0.001). Cavitation occurred in 23/38 (61%) MRI and 50/70 (70%) CT scans. We identified periventricular white matter lesions as a predictor of cavity formation by MRI and CT. CONCLUSION: Acute DWI significantly overestimates final infarct size. A third of lacunar infarcts do not develop a cavity.

A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes.

BACKGROUND: Left ventricular mass (LVM) is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC). In the present study, we use association analysis to further study the genetic effect on LVM. METHODS: Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets. RESULTS: In the overall analysis, the most significant association was found to rs10743465, downstream of the SOX5 gene (p = 1.27E-05). Also, 19 additional SNPs had nominal p < 0.001. In the subset analysis, the most significant difference in genetic effect between those with high and low WC occurred with rs1157480 (p = 1.37E-04 for the difference in ß coefficients), located upstream of TMTC1. Twelve additional SNPs in or near 6 genes had p < 0.001. CONCLUSIONS: The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. SOX5 may play an important role in the regulation of LVM. An interaction of TMTC1 with abdominal obesity may contribute to phenotypic variation of LVM.

Genome-wide linkage and peak-wide association study of obesity-related quantitative traits in Caribbean Hispanics.

Although obesity is more prevalent in Hispanics than non-Hispanic whites in the United States, little is known about the genetic etiology of the related traits in this population. To identify genetic loci influencing obesity in non-Mexican Hispanics, we performed a genome-wide linkage scan in 1,390 subjects from 100 Caribbean Hispanic families on six obesity-related quantitative traits: body mass index (BMI), body weight, waist circumference, waist-to-hip ratio, abdominal and average triceps skinfold thickness after adjusting for significant demographic and lifestyle factors. We then carried out an association analysis of the linkage peaks and the FTO gene in an independent community-based Hispanic subcohort (N = 652, 64% Caribbean Hispanics) from the Northern Manhattan Study. Evidence of linkage was strongest on 1q43 with multipoint LOD score of 2.45 (p = 0.0004) for body weight. Suggestive linkage evidence of LOD > 2.0 was also identified on 1q43 for BMI (LOD = 2.03), 14q32 for abdominal skinfold thickness (LOD = 2.17), 16p12 for BMI (LOD = 2.27) and weight (LOD = 2.26), and 16q23-24 for average triceps skinfold thickness (LOD = 2.32). In the association analysis of 6,440 single nucleotide polymorphisms (SNPs) under 1-LOD unit down regions of our linkage peaks on chromosome 1q43 and 16p12 as well as in the FTO gene, we found that two SNPs (rs6665519 and rs669231) on 1q43 and one FTO SNP (rs12447427) were significantly associated with BMI or body weight after adjustment for multiple testing. Our results suggest that in addition to FTO, multiple genetic loci, particularly those on 1q43 region, may contribute to the variations in obesity-related quantitative traits in Caribbean Hispanics.

Genetic linkage of serum homocysteine in Dominican families: the Family Study of Stroke Risk and Carotid Atherosclerosis.

BACKGROUND AND PURPOSE: Homocysteine levels are determined by genetic and environmental factors. Several studies have linked high plasma levels of total homocysteine to the increased risk of cardiovascular disease, stroke, and many other conditions. However, the exact mechanism of documented and novel total homocysteine quantitative trait loci to that risk is unknown. METHODS: We have performed linkage analysis in 100 high-risk Dominican families with 1362 members. Probands were selected from the population-based Northern Manhattan Study. A set of 405 microsatellite markers was used to screen the whole genome. Variance components analysis was used to detect evidence for linkage after adjusting for stroke risk factors. Ordered-subset analysis based on Dominican Republic enrollment was conducted. RESULTS: Total homocysteine levels had a heritability of 0.44 (P<0.0001). The most significant evidence for linkage was found at chromosome 17q24 (maximum logarithm of odds [MLOD]=2.66, P=0.0005) with a peak at D17S2193 and was significantly increased in a subset of families with a high proportion of Dominican Republic enrollment (MLOD=3.92, P=0.0022). Additionally, modest evidence for linkage was found at chromosome 2p21 (MLOD=1.77, P=0.0033) with a peak at D2S1356 and was significantly increased in a subset of families with a low proportion of Dominican Republic enrollment (MLOD=2.82, P=0.0097). CONCLUSIONS: We found a strong evidence for novel quantitative trait loci on chromosomes 2 and 17 for total homocysteine plasma levels in Dominican families. Our family study provides essential data for a better understanding of the genetic mechanisms associated with elevated total homocysteine levels leading to cardiovascular disease after accounting for environmental risk factors.