RESUMO
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.
Assuntos
Dislipidemias/etnologia , Etnicidade/estatística & dados numéricos , Hipertensão/etnologia , Fumar/etnologia , Acidente Vascular Cerebral Lacunar/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Região do Caribe/etnologia , Feminino , Florida/epidemiologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Masculino , Microcirculação , Pessoa de Meia-Idade , Fatores de Risco , População Branca/estatística & dados numéricosRESUMO
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.
Assuntos
Coagulação Sanguínea/genética , Doenças das Artérias Carótidas/genética , Placa Aterosclerótica/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Polimorfismo de Nucleotídeo Único , Trombospondina 1/genética , Fator de von Willebrand/genética , Idade de Início , Idoso , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , República Dominicana/etnologia , Dislipidemias/epidemiologia , Epistasia Genética/genética , Feminino , Seguimentos , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Haplótipos , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/epidemiologia , Inibidor 1 de Ativador de Plasminogênio/fisiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologia , Trombospondina 1/fisiologia , Ultrassonografia , Fator de von Willebrand/fisiologiaRESUMO
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, ORâ=â1.71, 95% CIâ=â1.23-2.37, Bonferroni-corrected pâ=â0.03) and for a number of plaques (rate ratio, RRâ=â1.31, 1.18-1.45, Bonferroni-corrected pâ=â1.4×10(-5)), whereas T-carriers of the UCP5 SNP rs5977238 had an decreased risk for carotid plaque (ORâ=â0.49, 95% CIâ=â0.32-0.74, Bonferroni-corrected pâ=â0.02) and plaque number (RRâ=â0.64, 95% CIâ=â0.52-0.78, Bonferroni-corrected pâ=â4.9×10(-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.