Biomedical subjects

Marcella A Wozniak

Publications and source records attributed to Marcella A Wozniak.

8 recordsLinked to original sources

PubMed2006

Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study.

An association between polymorphisms within the phosphodiesterase 4D gene (PDE4D) and ischemic stroke was initially reported in older adults from Iceland and has been supported by studies in several other primarily elderly populations. In the present study, we examined the association between PDE4D polymorphisms and early-onset ischemic stroke in a biracial female population. A systematic search for polymorphisms in the highly evolutionary conserved regions of PDE4D was performed on 48 African-American and 48 Caucasian participants. Novel and known polymorphisms were then prioritized and genotyped in the entire study population of 224 cases of first ischemic stroke among women aged 15-49 and 211 age- and ethnicity-balanced control subjects. Forty novel and previously reported polymorphisms with a minor allele frequency greater than 0.05 were determined, with 23 polymorphisms selected for analysis in the full case-control sample. Single nucleotide polymorphism (SNP), linkage disequilibrium and haplotype analyses were performed. SNP rs918592, found in an intron near the 5' end of the gene, was significantly associated with stroke (age- and race-adjusted odds ratio (OR=1.5, P=0.007), with four other SNPs showing significant, albeit less strong, associations. The magnitude of association was similar across African-Americans and Caucasians and across multiple stroke subtypes (e.g. atherosclerotic, lacunar and non-lacunar of undetermined etiology). The association of rs918592 with stroke was confined exclusively to current smokers (OR=3.2, P=0.00014), with no association observed among never-smokers (OR=0.9, P=0.75) or former smokers (OR=1.2, P=0.66), demonstrating a gene-environment interaction (P=0.03). A strong dose-response relationship was also seen among current smokers. No specific risk haplotypes were identified.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

Preeclampsia and the risk of ischemic stroke among young women: results from the Stroke Prevention in Young Women Study.

BACKGROUND AND PURPOSE: Preeclampsia is a pregnancy-specific systemic syndrome of unknown cause that affects 3% to 8% of pregnancies in the United States. Although preeclampsia is known to be an important risk factor for pregnancy-associated stroke, few data exist with regard to its association with stroke not occurring during pregnancy or the postpartum period. METHODS: Using data from the Stroke Prevention in Young Women Study (SPYW), a population-based case-control study of risk factors for ischemic stroke in women aged 15 to 44 years (recruitment period: 1992 to 1996, SPYW-1; 2001 to 2003, SPYW-2), we examined the independent association between a history of preeclampsia and the likelihood of ischemic stroke. Odds ratios (ORs) and 95% CIs were estimated using logistic regression. Cases (n=261) were women with stroke in the greater Baltimore-Washington area, and controls (n=421) were women free of a history of stroke identified by random digit dialing. Women who were pregnant at the time of stroke, those whose stroke occurred within 42 days postpartum, and nulligravida women were excluded from the analysis. RESULTS: The prevalence of preeclampsia among cases and controls was 15% (SPYW-1: 16%; SPYW-2: 15%) and 10% (SPYW-1: 10%; SPYW-2: 11%), respectively. Preeclampsia was associated with an increased likelihood of ischemic stroke (crude OR: 1.59; 95% CI: 1.00 to 2.52). After multivariable adjustment for age, race, education, and number of pregnancies, women with a history of preeclampsia were 60% more likely to have a nonpregnancy-related ischemic stroke than those without a history of preeclampsia (OR: 1.63; 95% CI: 1.02 to 2.62). Similar patterns were observed for women who reported symptoms of preeclampsia (elevated blood pressure and proteinuria). CONCLUSIONS: These results suggest an association between a history of preeclampsia and ischemic stroke remote from pregnancy. If these results are confirmed in other studies, evaluation of the importance of targeting women with preeclampsia for close risk factor monitoring and control beyond the postpartum period may be warranted.

Adolescent↗

PubMed2006

Familial aggregation of ischemic stroke in young women: the Stroke Prevention in Young Women Study.

BACKGROUND AND PURPOSE: Stroke occurs infrequently in young adults. While a familial basis for older onset stroke is well established, the extent of familial clustering in young-onset stroke is unknown. To address this issue, we compared the frequency of stroke in relatives of stroke cases to that in relatives of controls across different ages and by stroke subtype. METHODS: Through a population-based case-control study of stroke, we identified 487 women aged 15-49 years with ischemic stroke and 615 women without stroke matched by age and geographic region. Family history of stroke was collected for 5,749 relatives (parents and siblings) of case and control probands by standardized interview. RESULTS: Strokes were reported in 149 relatives of case patients and 119 relatives of controls. Siblings of stroke case patients had more than four times the risk of stroke compared to siblings of controls (OR, 4.17; 95% CI, 1.9-8.8) and mothers of stroke case patients had twice the risk of stroke compared to mothers of control subjects (OR, 2.02; 95% CI, 1.4-3.0). The association between stroke in probands and family history of stroke was strongest among women aged 15-24 years (OR, 2.5; 95% CI, 0.4-15.1), and diminished with increasing proband age (OR, 1.6; 95% CI, 0.8-3.3 among women 25-34 years and OR, 1.5; 95% CI, 1.1-1.9 among women 35-49 years; P<0.0001 for trend). CONCLUSIONS: We conclude that young-onset stroke aggregates in families and that the magnitude of aggregation increases with decreasing proband age.

Adolescent↗

PubMed2005

Promoter polymorphisms in the nitric oxide synthase 3 gene are associated with ischemic stroke susceptibility in young black women.

BACKGROUND AND PURPOSE: Endothelial nitric oxide exerts a variety of protective effects on endothelial cells and blood vessels, and therefore the nitric oxide synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility. METHODS: We used the population-based Stroke Prevention in Young Women case-control study to assess the association of five NOS3 polymorphisms in 110 cases (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the promoter region (-1468 T>A, -922 G>A, -786 T>C), 1 SNP in exon 7 (G894T), and 1 insertion/deletion polymorphism within intron 4. RESULTS: Significant associations with both the -922 G>A and -786 T>C SNPs with ischemic stroke were observed in the black, but not the white, population. This association was attributable to an increased prevalence of the -922 A allele (OR=3.0, 95% CI=1.3 to 6.8; P=0.005) and the -786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in cases versus controls. These 2 SNPs were in strong linkage disequilibrium (D'=1.0), making it impossible to determine, within the confines of this genetic study, whether 1 or both of these polymorphisms are functionally related to NOS3 expression. Two sets of haplotypes were also identified, 1 of which may confer an increased susceptibility to stroke in blacks, whereas the other appears to be protective. CONCLUSIONS: Promoter variants in NOS3 may be associated with ischemic stroke susceptibility among young black women.

Adolescent↗

PubMed2004

Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study.

BACKGROUND: The genes encoding proteins in the thrombomodulin-protein C pathway are promising candidate genes for stroke susceptibility because of their importance in thrombosis regulation and inflammatory response. Several published studies have shown that the Ala455Val thrombomodulin polymorphism is associated with ischemic heart disease, but none has examined the association with stroke. Using data from the Stroke Prevention in Young Women Study, we sought to determine the association between the Ala455Val thrombomodulin polymorphism and the occurrence of ischemic stroke in young women. METHODS: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. We compared 141 cases of first ischemic stroke (44% black) among women 15 to 44 years of age with 210 control subjects (35% black) who were identified by random digit dialing and frequency matched to the cases by age and geographical region of residence. Data on historical risk factors were collected by standardized interview. Genotyping of the thrombomodulin Ala455Val polymorphism was performed by pyrosequencing. RESULTS: The A allele (frequency = 0.85) was associated with stroke under the recessive model. After adjustment for age, race, cigarette smoking, hypertension, and diabetes, the AA genotype, compared with the AV and VV genotypes combined, was significantly associated with stroke (odds ratio 1.9, 95% CI 1.1-3.3). The AA genotype was more common among black than white control subjects (81% versus 68%) but there was no significant interaction between the risk genotype and race (adjusted odds ratio 2.7 for blacks and 1.6 for whites). A secondary analysis removing all probable (n = 16) and possible (n = 15) cardioembolic strokes demonstrated an increased association (odds ratio 2.2, 95% CI 1.2-4.2). CONCLUSIONS: Among women aged 15 to 44 years, the AA genotype is more prevalent among blacks than whites and is associated with increased risk of early onset ischemic stroke. Removing strokes potentially related to cardioembolic phenomena increased this association. Further studies are needed to determine whether this polymorphism is functionally related to thrombomodulin expression or whether the association is due to population stratification or linkage to a nearby functional polymorphism.

Adolescent↗

PubMed2003

Acquired immunodeficiency syndrome and the risk of stroke.

BACKGROUND AND PURPOSE: Although acquired immunodeficiency syndrome (AIDS) is thought to increase the risk of stroke, few data exist to quantify this risk. This is the first population-based study to quantify the AIDS-associated risk of stroke. METHODS: We identified all incident ischemic stroke (IS) and intracerebral hemorrhage (ICH) cases among young adults 15 to 44 years of age in central Maryland and Washington, DC, who were discharged from any of the 46 hospitals in the study area in 1988 and 1991. Using data from the medical records, 2 neurologists reviewed each case to confirm the diagnosis. Cases of AIDS among these patients with stroke were defined using Centers for Disease Control and Prevention criteria (1987). The number of cases of AIDS in the central Maryland and Washington population during 1988 and 1991 was determined from regional health departments working with the Centers for Disease Control and Prevention. Poisson regression was used to estimate the age-, race-, and sex-adjusted relative risk of stroke associated with AIDS. RESULTS: There were 385 IS cases (6 with AIDS) and 171 ICH cases (6 with AIDS). The incidences of IS and ICH among persons with AIDS were both 0.2% per year. AIDS conferred an adjusted relative risk of 13.7 (95% confidence interval [CI], 6.1 to 30.8) for IS and 25.5 (95% CI, 11.2 to 58.0) for ICH. After exclusion of 5 cases of stroke in AIDS patients in whom other potential causes were identified, AIDS patients continued to have an increased risk of stroke with an adjusted relative risk of 9.1 (95% CI, 3.4 to 24.6) for IS and 12.7 (95% CI, 4.0 to 40.0) for ICH. CONCLUSIONS: This population-based study found that AIDS is strongly associated with both IS and ICH.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Antiphospholipid antibodies and stroke in young women.

BACKGROUND AND PURPOSE: Antiphospholipid antibodies have been associated with ischemic stroke in some but not all studies. METHODS: We performed a population-based case-control study examining antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants) using stored frozen sera and plasma in 160 cases and 340 controls enrolled in the Stroke Prevention in Young Women study. We evaluated for the presence of anticardiolipin antibody (IgG, IgM, and IgA isotypes) by an enzyme-linked immunosorbent assay and for the lupus anticoagulant using several phospholipid-dependent coagulation tests (activated partial thromboplastin time, dilute Russell's viper venom time) with mixing studies. If mixing studies were prolonged, confirmatory tests were performed. RESULTS: A positive anticardiolipin antibody level of any isotype was seen in 43 cases (26.9%) and 62 controls (18.2%) (P=0.03), lupus anticoagulant in 29 cases (20.9%) and 38 controls (12.8%) (P=0.03), and either anticardiolipin antibody or lupus anticoagulant in 61 cases (42.1%) and 86 controls (27.9%) (P=0.003). After adjustment for age, current cigarette smoking, hypertension, diabetes, angina, ethnicity, body mass index, and high-density lipoprotein levels, the relative odds of stroke for women with anticardiolipin antibody immunoreactivity of any isotype or a lupus anticoagulant was 1.87 (95% confidence interval, 1.24 to 2.83; P=0.0027). CONCLUSIONS: The results from this study support the importance of antiphospholipid antibodies as an independent risk factor for stroke in young women.

Adolescent↗

PubMedDate not supplied

Return to work after ischemic stroke: a methodological review.

Despite the economic cost of lost employment, return to work after ischemic stroke has received little study. The percentages of patients working after stroke vary widely from 11 to 85%. Comparisons of these studies are difficult because they report return to work in different populations after diverse follow-up periods using variable definitions of stroke and work. Stroke severity as measured by activities of daily living was the most robust predictor of return to work. However, many factors known to influence vocational outcome after other illness (e.g., social and job characteristics) have not been examined. Directions for future studies of return to work are suggested.

Activities of Daily Living↗