Abstract only Introduction: Low dehydroepiandrosterone sulfate (DHEAS) levels recently have been related to elevated risk of ischemic stroke. However, the association between DHEAS and traditional ...cardiovascular risk factors remains unclear. Methods: Blood samples were collected in 1989-1990 among 32,826 participants of the Nurses’ Health Study. Samples were assayed for DHEAS, lipids, and other biomarkers as part of a nested case control study evaluating risk of ischemic stroke and 340 stroke-free controls with complete data were available. Lifestyle covariates were ascertained in 1988. Stepwise logistic regression models were used to evaluate the association of between CVD risk factors and low DHEAS (<42 μ g/dL), while stepwise linear regression was used to evaluate the association with continuous DHEAS. Stepwise models utilized an entry threshold of α=0.20 and exit criterion of α=0.10. Results: The mean level of DHEAS was 78.38 μ g/dL (s.d. 50.02; median=67.03) in this population of women aged 43-69 years (median=62). Age was strongly associated with lower DHEAS. Women with history of heart disease and higher total/HDL cholesterol were more likely to have low DHEAS. In stepwise logistic regression analyses, age (OR=2.94; 95%CI: 1.73-5.00 for 10 yrs) and history of heart disease (OR=1.84; 95% CI: 0.91-3.70) were identified as risk factors for low DHEAS. In stepwise linear regression modeling, age, postmenopausal hormone use, history of heart disease and C-reactive protein (CRP) were associated with lower DHEAS levels while alcohol use was associated with higher DHEAS levels (Table 1). Body mass index, smoking, diabetes, glycosylated hemoglobin and lipids were not associated with low DHEAS. Conclusions: In this population of healthy women, lower levels of DHEAS were associated with older age, history of heart disease, postmenopausal hormone use, higher CRP and lower levels of alcohol consumption. Further research is needed to explore these associations. Table 1 Multivariable * adjusted estimates for DHEAS by cardiovascular disease risk factors DHEAS (continuous μ g/dL) β † 95%CI Age ‡ −28.40 −36.75, -20.05 History of Heart disease −18.76 −39.23, 1.71 Postmenopausal Hormone Therapy Use & −12.01 −21.99, -2.04 CRP £ (mg/L) −0.66 −1.37, 0.04 Alcohol # (g/day) 2.95 0.46, 5.45 * All variables mutually adjusted for one another † Estimated from stepwise logistic regression model ‡ per 10 year increase in age & Ref = No use of postmenopausal hormone therapy £ per 1 unit increase in C-reactive protein (CRP- mg/L) # per 5 unit increase in alcohol consumption (g/day)
Abstract only Background and Purpose: High sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1) and fibrinogen are markers of systemic inflammation that have ...been associated with a greater risk and severity of total and ischemic stroke, as well as with elevated blood pressure, a primary risk factor for stroke. However, few studies have examined whether the role of these inflammatory risk factors on stroke pathophysiology is influenced by hypertension status. Methods: Blood samples were collected and assayed for hsCRP, sICAM-1, and fibrinogen among 27,330 initially healthy women from the Women’s Health Study who were followed from 1992-2014. Self-reported hypertension status, cardiovascular risk factors, lifestyle and alcohol consumption were obtained from the baseline questionnaire prior to randomization. New cases of stroke were ascertained by self-report on annual follow-up questionnaires and counted only if confirmed by medical records according to the National Survey of Stroke criteria. The primary outcome was total stroke with ischemic and hemorrhagic evaluated as secondary outcomes. Multivariable Cox models were utilized to estimate the overall association between each marker of inflammation and stroke, and also separately stratified by hypertension status. Results: We observed 629 incident total strokes over 477, 278 person-years. In overall multivariable analyses, the highest quartile of hsCRP and sICAM-1 were associated with a significantly greater risk of total stroke compared to the lowest quartile (hsCRP: HR=1.76, 95% CI: 1.38, 2.24, p-trend<0.001; sICAM-1: HR=1.29, 95% CI: 1.01, 1.65, p-trend =0.01). Fibrinogen was not significantly associated with risk of total stroke in multivariable models. All main effect estimates were attenuated when adjusted for baseline hypertension status. In analyses stratified by hypertension status at baseline, elevated hsCRP (extreme quartiles) was significantly associated with risk of total stroke only among prehypertensive (p-trend=0.03) and hypertensive women (p-trend=0.07), although the interaction was not statistically significant. In analyses by stroke type, the findings for ischemic stroke were similar to those of total stroke, while there was no significant association observed with hemorrhagic stroke for any of the measured markers of inflammation, among the limited number of events (n=111). Conclusions: In this cohort of women free of cardiovascular disease at baseline, elevated hsCRP and sICAM-1 were significantly associated with risk of stroke. Furthermore, the association between hsCRP and stroke may be restricted to prehypertensive and hypertensive women.
Abstract only
Background:
Low magnesium levels may be associated with higher blood pressure as well as endothelial dysfunction. Results from studies examining the association between serum magnesium ...and risk of stroke are inconsistent, with some studies suggesting a protective association with higher levels.
Methods:
Among 32,826 participants in the Nurses’ Health Study who provided blood samples in 1989-1990, ischemic strokes were identified and confirmed by medical records through 2006. We conducted a nested case-control analysis of 460 cases, matched to controls (1:1) on age, menopausal status, use of postmenopausal hormones, ancestry, date of blood draw, fasting status and smoking status. Magnesium quintiles were created based on the distribution of serum magnesium levels among controls, and a dichotomous variable was also created, based on prior data: low magnesium (<2.0 mg/dL) and high magnesium (≥ 2.0 mg/dL). Conditional logistic regression models were used to estimate the multivariable adjusted association of serum magnesium and the risk of ischemic stroke and unconditional analyses were used to assess effect modification.
Results:
In univariate analysis, median magnesium levels did not differ between stroke cases and controls (median=2.1 in each, p-value=0.16). Conditional on matching factors, women in the lowest magnesium quintile had a relative risk (RR) of 1.34 (95% confidence interval CI: 0.85-2.09) for ischemic stroke, compared to those in the highest quintile. Additional adjustment for potential confounders (alcohol intake, body mass index BMI, physical activity, aspirin use, thiazide diuretic use, history of diabetes, history of coronary heart disease, glycosylated hemoglobin and the ratio of total to HDL-cholesterol) did not substantially alter the risk estimates (RR=1.34; 95% CI: 0.82-2.17). However, women with magnesium levels <2.0mg/dL had a significant increase in the risk of ischemic stroke, compared to women with magnesium levels ≥2.0 (RR= 1.66; 95% CI: 1.18 - 2.34. Controlling for potential confounders (as above) did not significantly alter this risk (RR= 1.63; 95% CI: 1.13 - 2.36). No significant effect modification was observed by age, BMI, hypertension or diabetes.
Conclusions:
Serum magnesium levels <2.0 are associated with increased risk of ischemic stroke among this population of women.
Abstract only Introduction: Fetuin-A, a protein secreted primarily by the liver, has been associated with non-alcoholic fatty liver disease and insulin resistance. A recent study found that high ...fetuin-A levels were associated with increased cardiovascular risk, particularly for ischemic stroke; however, the data have not been replicated. Methods: A nested case-control design was utilized to examine the relationship between fetuin-A and ischemic stroke among female participants of the Nurses’ Health Study who provided blood samples. A total of 462 incident cases of ischemic stroke were identified and confirmed by medical records according to the National Survey of Stroke criteria between 1990-2006 and were matched to 462 controls by age, menopausal status, hormone therapy use, and smoking status. Fetuin-A was measured on blood samples collected and stored between 1989-1990. Conditional logistic regression was used to evaluate the multivariable adjusted association between fetuin-A and ischemic stroke. Results: Fetuin-A levels were higher in those with elevated cholesterol (p=0.02), current hormone use (p=0.002) and hypertension (p=0.05) in univariate analyses. Significant partial spearman correlations, adjusted for matching factors, were found between fetuin-A and triglycerides (r=0.18; p<0.001), C-reactive protein (r=0.12; p=0.002), and BMI (r=0.13; p<0.001). Fetuin-A quartiles were not significantly associated with increased risk of incident ischemic stroke when adjusted for matching factors, or when additionally adjusted for other CVD risk factors (see Table 1). Further adjustment for other biomarkers, modestly strengthened the association, but p for trend remained nonsignificant (p=0.37). Conclusions: In this population of women, fetuin-A was not significantly associated with a greater risk of ischemic stroke. Further research is needed to explore this association. Table 1 Multivariable adjusted relative risk (95% CI) of ischemic stroke by Fetuin-A quartiles Quartiles of Fetuin-A p-value for trend Q1 Q2 Q3 Q4 Range (μ g/mL) <377 377-<449 449-<526 526-1538 Cases/Controls 108/116 136/115 102/113 112/116 Model 1 * 1.00 1.22 (0.86-1.75) 0.92 (0.62-1.35) 1.05 (0.71-1.55) 0.79 Model 2 † 1.00 1.32 (0.88-1.99) 1.00 (0.64-1.56) 1.28 (0.81-2.01) 0.52 Model 3 ‡ 1.00 1.34 (0.88-2.03) 1.06 (0.67-1.69) 1.24 (0.78-1.98) 0.59 Model 4 § 1.00 1.41 (0.82-2.42) 1.00 (0.55-1.84) 1.33 (0.73-2.42) 0.37 * Model 1: Conditional on matching factors (age, menopausal status, hormone use, smoking) † Model 2: Model 1 + aspirin use, alcohol intake, physical activity, healthy diet score, current post-menopausal hormone use ‡ Model 3: Model 2 + aspirin use, alcohol intake, physical activity, healthy diet score, current post-menopausal hormone use, history of diabetes, elevated cholesterol, high blood pressure, and CHD or revascularization. § Model 4: Model 3+ HbA1c, ln(CRP), ln(triglycerides), ln(cholesterol/HDL)
IntroductionHigher levels of free and total testosterone (TT) and lower levels of sex hormone binding globulin (SHBG) have been associated with increased blood pressure (BP) in women with an inverse ...association between TT and BP reported among men. Fewer studies have examined dehydroepiandrosterone sulfate (DHEAS) or the association between sex steroid hormones and 24-hr ambulatory blood pressure (ABP) or blunted nocturnal BP fall.MethodsBaseline blood samples were assayed for 267 normotensive racially diverse men (≥50 years) and women (≥55 years) participating in the VITamin D and OmegA-3 TriaL (VITAL). Standardized seated BP (systolic SBP and diastolic DBP) and 24-hr ABP were measured by trained technicians. All participants provided extensive baseline self-reported data on relevant cardiovascular risk factors and sociodemographic covariates. Linear regression models adjusted for age, sex, race, body mass index, smoking, alcohol, multivitamin use, and fruit and vegetable intake estimated the association between each sex hormone and measures of BP and 24-hr ABP separately by sex. We used logistic regression to estimate (OR, 95% CI) the association between each sex hormone and blunted nocturnal fall, defined as a >10% reduction in SBP or DBP during sleeping hours.ResultsDHEAS, TT and SHBG were not significantly correlated with measures of BP when simultaneously adjusted for one another. In multivariable analyses stratified by sex, among women there was no association observed between sex hormones and measures of BP. Among men, each 10% increase in DHEAS was associated with a 0.45 mmHg increase in seated DBP (β=4.45, 95% CI0.71, 8.18) and each 10% increase in TT and SHBG was associated with a 0.67 mmHg (β=-6.73, 95% CI:-11.47, -1.99) and 0.72 mmHg (β=-7.23, 95% CI-12.05, -2.41) decrease in seated DBP, respectively.ConclusionsWe observed significant inverse cross-sectional associations between DHEAS, TT and SHBG with seated DBP in men, but not SBP, 24-hr ABP or blunted nocturnal BP. There was no association observed between sex hormones and measures of BP among women. Further research is needed to understand how sex hormones may impact BP measures over time.
Light-to-moderate alcohol consumption has been consistently associated with lower risk of heart disease, but data for stroke are less certain. A lower risk of stroke with light-to-moderate alcohol ...intake has been suggested, but the dose response among women remains uncertain and the data in this subgroup have been sparse.
A total of 83 578 female participants of the Nurses' Health Study who were free of diagnosed cardiovascular disease and cancer at baseline were followed-up from 1980 to 2006. Data on self-reported alcohol consumption were assessed at baseline and updated approximately every 4 years, whereas stroke and potential confounder data were updated at baseline and biennially. Strokes were classified according to the National Survey of Stroke criteria.
We observed 2171 incident strokes over 1 695 324 person-years. In multivariable adjusted analyses, compared to abstainers, the relative risks of stroke were 0.83 (95% CI, 0.75-0.92) for <5 g/d, 0.79 (95% CI, 0.70-0.90) for 5 to 14.9 g/d, 0.87 (0.72-1.05) for 15 to 29.9 g/d, and 1.06 (95% CI, 0.86-1.30) for 30 to 45 g/d. Results were similar for ischemic and hemorrhagic stroke.
Light-to-moderate alcohol consumption was associated with a lower risk of total stroke. In this population of women with modest alcohol consumption, an elevated risk of total stroke related to alcohol was not observed.
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