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ABSTRACT: Joint exposure to oral conjugated equine estrogen (CEE) and prothrombotic genetic variants factor II G20210A or factor V G1601A (Leiden) increase venous thrombotic risk 6- to 16-fold in postmenopausal women. Esterified estrogen (EE), an alternative estrogenic compound, appears not to be associated with increased risk and nothing is known about the joint risk with prothrombotic genetic variants.
We conducted a population-based, case-control study among postmenopausal women within a health maintenance organization. Subjects included 328 cases who sustained a first venous thrombosis and 1591 controls. Current hormone use was defined using electronic pharmacy records and variants FII G20210A and FV Leiden were genotyped using blood samples. FII and FV Leiden variants were associated with 2.1-fold and 3.7-fold increases in venous thrombotic risk, respectively. Overall, CEE use was associated with a 2.5-fold increase in risk compared with no hormone use, whereas EE use was not associated with a statistically increased risk. Compared with no hormone use and no variant, joint exposure to CEE and either prothrombotic variant was associated with an odds ratio (OR) of 9.1 (95% CI: 4.5 to 18.2), whereas joint exposure to EE and either variant was associated with an OR of 2.1 (0.6 to 6.8). When analyses were restricted to hormone users with either variant, CEE use was associated with an OR of 5.3 (1.3 to 21.7) compared with EE use.
These findings need replication and suggest EE use is associated with less risk than CEE use especially among 5% to 10% of women who are carriers of a prothrombotic variant.
Arteriosclerosis Thrombosis and Vascular Biology 01/2007; 26(12):2807-12. · 6.37 Impact Factor
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ABSTRACT: Intake of trans fatty acids is associated with increased risk of coronary heart disease. Whether different classes of trans fatty acids show similar associations is unclear. We previously reported an association of sudden cardiac death with red cell membrane trans-18:2 but not trans-18:1 fatty acids. To extend these findings, we investigated the associations of plasma phospholipid trans fatty acids with fatal ischemic heart disease (IHD) and sudden cardiac death.
We conducted a case-control study nested in the Cardiovascular Health Study. We identified 214 cases of fatal IHD (fatal myocardial infarction and coronary heart disease death) between 1992 and 1998. We randomly selected 214 controls, matched to cases on demographics, prevalent cardiovascular disease, and timing of blood draw. Plasma phospholipid fatty acids were assessed in blood samples collected earlier. Higher levels of plasma phospholipid trans-18:2 fatty acids were associated with higher risk of fatal IHD (odds ratio [OR] for interquintile range 1.68, 95% confidence interval [CI] 1.21 to 2.33) after adjustment for risk factors and trans-18:1 levels. Trans-18:1 levels above the 20th percentile were associated with lower risk (OR 0.34, 95% CI 0.18 to 0.63). In analyses limited to cases of sudden cardiac death (n=95), higher levels of trans-18:2 fatty acids were associated with higher risk (OR 2.34, 95% CI 1.27 to 4.31) and higher trans-18:1 with lower risk (OR 0.18, 95% CI 0.06 to 0.54).
Higher levels of trans-18:2 and lower levels of trans-18:1 fatty acids are associated with higher risks of fatal IHD and sudden cardiac death. If confirmed, these findings suggest that current efforts at decreasing trans fatty acid intake in foods should take into consideration the trans-18:2 content.
Circulation 08/2006; 114(3):209-15. · 14.74 Impact Factor
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ABSTRACT: Sudden cardiac death (SCD) is usually due to ventricular fibrillation and can occur as a first manifestation of heart disease. Prevention of ventricular fibrillation and SCD with n-3 polyunsaturated fatty acids is well documented. Trans-fatty acids (TFA) in the diet and cell membranes might affect the risk of SCD as well. We review evidence from an observational study that high levels of trans-18:2 (9 cis-, 12 trans- and 9 trans-, 12 cis-isomers of linoleic acid) in red blood cell membranes are associated with markedly higher risk of SCD. In contrast, cell membrane levels of trans-18:1 (trans-isomers of oleic acid), the major TFA in foods, do not appear associated with higher risk of SCD. While further studies are needed to investigate possible effects of trans-18:2 on arrhythmia, it would be prudent to limit dietary intake of trans-18:2.
Atherosclerosis Supplements 06/2006; 7(2):13-5. · 1.70 Impact Factor
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ABSTRACT: Genetic variants in coagulation factors are associated with myocardial infarction and may modify the association between hormone therapy and cardiovascular disease risk. This study assessed whether common variation in the prothrombin gene was associated with incident nonfatal myocardial infarction in postmenopausal women and whether this association differed according to current estrogen use. Eight variants representing 98% of common prothrombin variants were selected using publicly available genomic variation data. These variants and the functional G20210A variant were genotyped and used to infer haplotypes in a population-based Washington State case-control study of postmenopausal Caucasian women (1995-1999; 273 cases and 788 controls). Women carrying a nonsynonymous polymorphism in exon 6 (C5467T) had an increased risk of myocardial infarction (for each additional copy, relative to women with one fewer copy, odds ratio = 1.4, 95% confidence interval: 1.0, 1.8). Prothrombin haplotypes were also associated with myocardial infarction (with minimal adjustment, global p = 0.056; with full adjustment, p = 0.034). Associations between haplotypes and myocardial infarction were similar among users of hormone therapy and nonusers (global p = 0.61), though statistical power was limited. These preliminary results suggest that common genetic variants in the prothrombin gene or other variants in linkage disequilibrium are associated with myocardial infarction in postmenopausal women.
American Journal of Epidemiology 05/2006; 163(7):600-7. · 5.22 Impact Factor
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Nona Sotoodehnia,
David S Siscovick,
Matteo Vatta,
Bruce M Psaty,
Russell P Tracy,
Jeffrey A Towbin, Rozenn N Lemaitre,
Thomas D Rea,
J Peter Durda,
Joel M Chang,
Thomas S Lumley,
Lewis H Kuller,
Gregory L Burke,
Susan R Heckbert
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ABSTRACT: Sympathetic activation influences the risk of ventricular arrhythmias and sudden cardiac death (SCD), mediated in part by the beta2-adrenergic receptor (B2AR). We investigated whether variation in the B2AR gene is associated with SCD risk.
In this study, 4441 white and 808 black Cardiovascular Health Study (CHS) participants were followed up prospectively for SCD and genotyped for B2AR Gly16Arg and Gln27Glu polymorphisms. The study was replicated in 155 case and 144 control white subjects in a population-based case-control study of SCD, the Cardiac Arrest Blood Study (CABS). In CHS, Gly16 and Gln27 allele frequencies were 62.4% and 57.1% among white and 50.1% and 81.4% among black participants. Over a median follow-up of 11.1 years, 156 and 39 SCD events occurred in white and black participants, respectively. The Gln27Glu variant was associated with SCD risk (P=0.008 for general model). SCD risk was higher in Gln27 homozygous participants than in Glu27 carriers (ethnicity-adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.17 to 2.09; P=0.003). The increased risk did not differ significantly between white (HR, 1.62; 95% CI, 1.18 to 2.23) and black (HR, 1.23; 95% CI, 0.61 to 2.48) participants, although the confidence interval was wide in blacks. In the CABS replication study, Gln27 homozygous participants similarly had higher SCD risk than Glu27 carriers (odds ratio, 1.64; 95% CI, 1.02 to 2.63; P=0.040). Gly16Arg was not associated with SCD risk in either study.
Gln27 homozygous individuals have an increased risk of SCD in 2 study populations. Our findings suggest that B2AR plays a role in SCD in humans. Study of genetic variation within the B2AR gene may help identify those at increased SCD risk.
Circulation 05/2006; 113(15):1842-8. · 14.74 Impact Factor
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ABSTRACT: Clinical trials of conjugated equine estrogen (CEE) or estradiol vs placebo in postmenopausal women have found no effect or an elevated risk of myocardial infarction (MI) and stroke. The association of these end points with the use of esterified estrogen (EE) is unknown.
We examined the risk of MI and stroke associated with current use of CEE, use of EE, or nonuse of hormones in a population-based case-control study in a health maintenance organization. Cases were all postmenopausal women with an incident MI (n = 1644) or stroke (n = 1080). Controls (n = 4205) consisted of a random sample of postmenopausal women without MI or stroke. Current use of postmenopausal hormones was assessed using a computerized pharmacy database.
There was no difference in risk of MI or stroke associated with current use of CEE or EE compared with nonuse or for current use of CEE compared with EE. In analyses restricted to hormone users, there was a suggestion of higher ischemic stroke risk associated with CEE alone (without progestin) compared with EE alone (odds ratio, 1.57; 95% confidence interval, 0.98-2.53). There was also a suggestion that when initiated in the previous 6 months, CEE was associated with a higher risk of MI than EE (odds ratio, 2.33; 95% confidence interval, 0.93-5.82).
Further study may be warranted of the effects of EE on the risk of cardiovascular end points.
Archives of Internal Medicine 03/2006; 166(4):399-404. · 11.46 Impact Factor
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ABSTRACT: The utility of fatty acids (FAs) as biomarkers of total fat intake is unknown.
We compared FA changes in red cells (RCs), plasma phospholipids (PLs), and cholesterol esters (CEs) in response to a low-fat diet (LFD) and a moderate-fat diet (MFD) and assessed whether individual or combination of FAs predict LFD.
Postmenopausal women (n = 66) were randomly assigned to receive an LFD (17% of energy from fat) or an MFD (34% of energy from fat) for 6 wk. All foods were provided. FAs in diets and blood were determined by gas-liquid chromatography. FA changes between baseline and end of study were compared across diets by using t tests. FA predictors of an LFD were selected by logistic regression.
Many FAs in RCs, PLs, and CEs responded differently to the 2 diets. Changes from baseline with an LFD for palmitic acid (16:0) (3-11% increase), behenic (22:0) and lignoceric (24:0) acids (3-20% decrease, in RCs and PLs only), cis-monounsaturated FA (MUFA) (25-35% increase), linoleic acid (18:2n-6) (11-13% decrease), trans octadecanoic acids (trans 18:1) (7-20% decrease), and n-6 highly unsaturated FA (HUFA) (2-8% increase) were significantly different from changes with an MFD. Individually, 18:2n-6 and trans 18:1 were strong predictors of an LFD [receiver operating characteristic (ROC) curves: 0.92-0.80). A logistic regression model with trans 18:1, 18:2n-6, and vaccenic acid (18:1n-7) predicted an LFD with high specificity and sensitivity (ROC curves: 0.99).
Saturated FA, cisMUFA, n-6 HUFA, and exogenous FAs greatly differed in their response to the LFD and MFD. Parallel responses were observed in RCs, PLs, and CEs. A model with a combination of FAs almost perfectly differentiated the consumption of 34% fat from that of 17% fat.
American Journal of Clinical Nutrition 02/2006; 83(2):227-36. · 6.67 Impact Factor
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ABSTRACT: Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure (CHF).
The incidence and health burden of CHF are rising, particularly in older persons. Although n-3 fatty acids have effects that could favorably influence risk of CHF, the relation between fish intake and CHF incidence is unknown.
Among 4,738 adults age > or =65 years and free of CHF at baseline in 1989-90, usual dietary intake was assessed using a food frequency questionnaire. In a participant subsample, consumption of tuna or other broiled or baked fish, but not fried fish, correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was prospectively adjudicated.
During 12 years' follow-up, 955 participants developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was inversely associated with incident CHF, with 20% lower risk with intake 1 to 2 times/week (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.64 to 0.99), 31% lower risk with intake 3 to 4 times/week (HR = 0.69, 95% CI = 0.52 to 0.91), and 32% lower risk with intake > or =5 times/week (HR = 0.68, 95% CI = 0.45 to 1.03), compared with intake <1 time/month (p trend = 0.009). In similar analyses, fried fish consumption was positively associated with incident CHF (p trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF (p trend = 0.009), with 37% lower risk in the highest quintile of intake (HR = 0.73, 95% CI = 0.57 to 0.94) compared with the lowest.
Among older adults, consumption of tuna or other broiled or baked fish, but not fried fish, is associated with lower incidence of CHF. Confirmation in additional studies and evaluation of potential mechanisms is warranted.
Journal of the American College of Cardiology 07/2005; 45(12):2015-21. · 14.16 Impact Factor
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ABSTRACT: Although cholesterol is an important risk factor for coronary heart disease (CHD) among hypertensives, the burden of CHD among hypertensives that may be due to elevated cholesterol has not been well documented. This study aimed to estimate the proportion of incident myocardial infarction (MI) among hypertensives that may be attributable to elevated total cholesterol, and to investigate how well the National Cholesterol Education Program Adult Treatment Panel III (ATP III) classification method represents risk of MI among hypertensives.
A population-based, case-control study of patients aged 30 to 79 years enrolled in a health maintenance organization, treated pharmacologically for hypertension, and who were not using lipid-lowering medication. Cases were diagnosed with an incident fatal or nonfatal MI between 1986 and 2000 (n = 1535). Controls were randomly sampled and frequency-matched to cases by sex, 10-year age category, and year of event (n = 3743). Subjects' most recent total cholesterol values were categorized according to ATP III guidelines.
Overall, 31% (95% confidence interval: 23-39) of incident MIs among hypertensives could be explained by total cholesterol level above the optimal level of 200 mg/dL. Among participants in the highest ATP III risk stratum, 41% (95% confidence interval: 9-62) of the incident MIs were attributable to total cholesterol levels >160 mg/dL, but total cholesterol >or=200 mg/dL accounted for the majority of these excess events.
The ATP III risk stratification approach improves detection of the CHD burden due to elevated total cholesterol among hypertensives at highest risk. A strategy to improve cholesterol control in hypertensive patients might prevent a substantial part of the burden of morbidity and mortality from MI.
American Journal of Hypertension 06/2005; 18(6):759-66. · 3.18 Impact Factor
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ABSTRACT: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential.
Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained.
During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke.
Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.
Archives of Internal Medicine 02/2005; 165(2):200-6. · 11.46 Impact Factor
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ABSTRACT: Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds.
To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers.
This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first venous thrombosis between January 1995 and December 2001 and controls were matched on age, hypertension status, and calendar year.
Risk of first venous thrombosis in relation to current use of esterified or conjugated equine estrogens, with or without concomitant progestin. Current use was defined as use at thrombotic event for cases and a comparable reference date for controls.
Five hundred eighty-six incident venous thrombosis cases and 2268 controls were identified. Compared with women not currently using hormones, current users of esterified estrogen had no increase in venous thrombotic risk (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69-1.22). In contrast, women currently taking conjugated equine estrogen had an elevated risk (OR, 1.65; 95% CI, 1.24-2.19). When analyses were restricted to estrogen users, current users of conjugated equine estrogen had a higher risk than current users of esterified estrogen (OR, 1.78; 95% CI, 1.11-2.84). Among conjugated equine estrogen users, increasing daily dose was associated with increased risk (trend P value = .02). Among all estrogen users, concomitant progestin use was associated with increased risk compared with use of estrogen alone (OR, 1.60; 95% CI, 1.13-2.26).
Our finding that conjugated equine estrogen but not esterified estrogen was associated with venous thrombotic risk needs to be replicated and may have implications for the choice of hormones in perimenopausal and postmenopausal women.
JAMA The Journal of the American Medical Association 11/2004; 292(13):1581-7. · 30.03 Impact Factor
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ABSTRACT: Lipids, through effects on the coagulation and fibrinolytic systems, may contribute to the development of venous thrombosis. This association has been investigated in a few studies, with conflicting results.
We conducted a population-based, case-control study at a health maintenance organization in Washington State, to assess the association of serum lipid levels with the risk of venous thrombosis. Cases were 477 postmenopausal women with a first venous thrombosis during January 1995 through December 2001. Control subjects (1986) were a random sample of postmenopausal women. Medical records, computerized pharmacy databases, and a cancer registry served to collect data on lipid levels and risk factors for thrombosis. Total cholesterol levels were not associated with venous thrombosis. Only high HDL cholesterol levels were associated with a decreased risk of venous thrombosis after adjustment for hospitalization, malignancy, height and weight, postmenopausal hormone therapy, and vascular disease (for high-density lipoprotein [HDL] cholesterol levels >1.79 mmol/L versus those <1.79 mmol/L; odds ratio [OR], 0.71; 95% confidence interval [CI], 0.52 to 0.97). In contrast, elevated triglyceride levels were associated with an increased risk (OR, 2.13; 95% CI, 1.34 to 3.37) for women with triglyceride levels >1.05 mmol/L compared with women with lower levels.
Elevated triglyceride levels were associated with a doubling of risk of venous thrombosis in postmenopausal women, whereas elevated HDL cholesterol levels were associated with a decreased risk.
Arteriosclerosis Thrombosis and Vascular Biology 10/2004; 24(10):1970-5. · 6.37 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is particularly common in the elderly. Although effects of fish intake, including potential antiarrhythmic effects, may favorably influence risk of AF, relationships between fish intake and AF incidence have not been evaluated.
In a prospective, population-based cohort of 4815 adults > or =age 65 years, usual dietary intake was assessed at baseline in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. AF incidence was prospectively ascertained on the basis of hospital discharge records and annual electrocardiograms. During 12 years' follow-up, 980 cases of incident AF were diagnosed. In multivariate analyses, consumption of tuna or other broiled or baked fish was inversely associated with incidence of AF, with 28% lower risk with intake 1 to 4 times per week (HR=0.72, 95% CI=0.58 to 0.91, P=0.005), and 31% lower risk with intake > or =5 times per week (HR=0.69, 95% CI=0.52 to 0.91, P=0.008), compared with <1 time per month (P trend=0.004). Results were not materially different after adjustment for preceding myocardial infarction or congestive heart failure. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of AF.
Among elderly adults, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower incidence of AF. Fish intake may influence risk of this common cardiac arrhythmia.
Circulation 08/2004; 110(4):368-73. · 14.74 Impact Factor
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ABSTRACT: Estimates of the incidence of out-of-hospital primary cardiac arrest (CA) have typically relied solely upon emergency medical service or death certificate records and have not investigated incidence in clinical subgroups. Overall and temporal patterns of CA incidence were investigated in clinically defined groups using systematic methods to ascertain CA. Estimates of incidence were derived from a population-based case-control study in a large health plan from 1986 to 1994. Subjects were enrollees aged 50 to 79 years who had had CA (n = 1,275). A stratified random sample of enrollees who had not had CA was used to estimate the population at risk with various clinical characteristics (n = 2,323). Poisson's regression was used to estimate incidence overall and for 3-year time periods (1986 to 1988, 1989 to 1991, and 1992 to 1994). The overall CA incidence was 1.89/1,000 subject-years and varied up to 30-fold across clinical subgroups. For example, incidence was 5.98/1,000 subject-years in subjects with any clinically recognized heart disease compared with 0.82/1,000 subject-years in subjects without heart disease. In subgroups with heart disease, incidence was 13.69/1,000 subject-years in subjects with prior myocardial infarction and 21.87/1,000 subject-years in subjects with heart failure. Risk decreased by 20% from the initial to the final time period, with a greater decrease observed in those with (25%) compared with those without (12%) clinical heart disease. Thus, CA incidence varied considerably across clinical groups. The results provide insights regarding absolute and population-attributable risk in clinically defined subgroups, information that may aid strategies aimed at reducing mortality from CA.
The American Journal of Cardiology 07/2004; 93(12):1455-60. · 3.37 Impact Factor
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ABSTRACT: The ThrThr genotype of the angiotensinogen (AGT) Met235Thr polymorphism has been associated with elevated AGT levels, hypertension, increased heart disease risk, and improved blood pressure (BP) response to angiotensin-converting enzyme (ACE) inhibitors. We hypothesized that risk of stroke or myocardial infarction (MI) associated with ACE inhibitor use varies by AGT genotype, with a larger protective effect of ACE inhibitors in individuals with the ThrThr genotype than individuals who are carriers of the Met allele.
We conducted a population-based case-control study. Participants were health maintenance organization members aged 30 to 79 years with treated hypertension. Those who survived incident stroke (n = 116) or MI (n = 208) during the study period were designated as cases. Control subjects (n = 717) were randomly sampled and frequency-matched to MI cases on age, sex, and calendar year. Health history, medication use, and AGT genotype were assessed.
ThrThr genotype was present in 21% of stroke cases, 26% of MI cases, and 19% of control subjects. Compared with nonuse, ACE inhibitor use was associated with lower stroke risk among Thr homozygotes (odds ratio [OR] = 0.37, 95% CI = 0.14 to 0.99) than among Met carriers (OR = 1.4, 95% CI = 0.88 to 2.4; P for interaction =.02). Compared with nonuse, ACE inhibitor use was associated with similar MI risk among Thr homozygotes (OR = 0.90, 95% CI = 0.62 to 1.3) and among Met carriers (OR = 1.2, 95% CI = 0.60 to 2.5; P for interaction = 0.5).
In this hypertensive population, the association of ACE inhibitor use with risk of nonfatal stroke varied by genotype. The protective association between ACE inhibitor use and nonfatal stroke risk among individuals with ThrThr genotype was not observed for nonfatal MI.
American Journal of Hypertension 01/2004; 16(12):1011-7. · 3.18 Impact Factor
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ABSTRACT: In prospective studies, hypokalemia has been shown to be associated with a subsequent increase in stroke risk in treated hypertensive adults after 4 to 16 years of follow-up. Stroke risk associated with more recent assessments of hypokalemia has not been examined.
We used data from an on-going, population-based, case-control study of incident stroke at Group Health Cooperative (GHC). Cases were treated hypertensive adults, 30 to 79 years old, who sustained an incident ischemic or hemorrhagic stroke between July 1989 and December 2000. Controls were GHC members without a history of stroke who met same inclusion criteria as cases. Serum potassium (K(+)) levels were collected from GHC laboratory database. Hypokalemia (< or =3.4 mM/L) was defined using the most recent serum K(+) measure in the year before the index date (event date for cases; random date within calendar year of identification for controls). Multivariate logistic regression estimated the relative risk of ischemic and hemorrhagic stroke.
Among 593 ischemic and 125 hemorrhagic stroke cases, and 2397 controls, few subjects were hypokalemic: 3%, 6%, and 2%, respectively. Using the normal range of serum K(+) as a reference (3.5 to 5.0 mM/L), hypokalemia was associated with an elevated risk of ischemic (odds ratio [OR]: 2.04; 95% confidence interval [CI]: 1.14-3.64) and hemorrhagic stroke (OR: 3.29; 95% CI: 1.45-7.48) in adjusted analyses. Associations were not modified by diuretic use.
In adults with treated hypertension, hypokalemia in the year before a stroke was associated with an increased risk of incident ischemic and hemorrhagic stroke independent of diuretic use when compared to normal serum K(+) levels.
American Journal of Hypertension 10/2003; 16(10):806-13. · 3.18 Impact Factor
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Alexander P Reiner,
Susan R Heckbert,
Hans L Vos,
Robert A S Ariëns, Rozenn N Lemaitre,
Nicholas L Smith,
Thomas Lumley,
Thomas D Rea,
Lucia A Hindorff,
Gina D Schellenbaum,
Frits R Rosendaal,
David S Siscovick,
Bruce M Psaty
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ABSTRACT: We hypothesized that possession of either of 2 functional coagulation factor XIII polymorphisms, one within subunit A (Val34Leu) and one within subunit B (His95Arg), might modulate the prothrombotic effects of estrogen and help to explain the variation in incidence of arterial thrombotic events among postmenopausal women using hormone replacement therapy. In a population-based case-control study of 955 postmenopausal women, we assessed the associations of factor XIII genotypes and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (MI). The presence of the factor XIIIA Leu34 allele was associated with a reduced risk of MI (odds ratio [OR] = 0.70, 95% confidence interval [95% CI] = 0.51-0.95). The presence of the factor XIIIB Arg95 allele had little association with MI risk. Neither factor XIII polymorphism alone significantly modified the association between the risk of MI and current estrogen use. In exploratory analyses, however, there was a significant factor XIII subunit gene-gene interaction. Compared to women homozygous for both common factor XIII alleles, the Arg95 variant was associated with a reduced risk of MI in the presence of the Leu34 variant (OR = 0.36, 95% CI = 0.17-0.75) but not in the absence of the Leu34 variant (OR = 1.11, 95% CI = 0.69-1.79). Moreover, among women who had at least 2 copies of the variant factor XIII alleles and were current estrogen users, the risk of MI was reduced by 70% relative to estrogen nonusers with fewer than 2 factor XIII variant alleles (P value for interaction =.03). If confirmed, these findings may permit a better assessment of the cardiovascular risks and benefits associated with postmenopausal estrogen therapy.
Blood 08/2003; 102(1):25-30. · 9.90 Impact Factor
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Circulation 07/2003; 107(21):2632-4. · 14.74 Impact Factor
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ABSTRACT: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF.
Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223).
At baseline, 62% were never users, 26% were past users, and 12% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95% confidence interval [95% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction).
Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.
Journal of Women s Health 06/2003; 12(4):341-50. · 1.57 Impact Factor
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ABSTRACT: People older than 65 years are the fastest-growing segment of the population and account for the majority of cardiovascular disease (CVD) morbidity, mortality, and health care expenditures. Additionally, the influence of dietary habits on risk may be less pronounced in elderly persons, when atherosclerosis is more advanced. However, few data address the influence of diet on CVD risk in this population.
To determine whether fiber consumption from fruit, vegetable, and cereal sources (including whole grains and bran) is associated with incident CVD in elderly persons.
Prospective cohort study conducted from 1989 to June 2000. Setting and
Population-based, multicenter study among 3588 men and women aged 65 years or older and free of known CVD at baseline in 1989-1990. Usual dietary fiber consumption was assessed at baseline (mean participant age, 72 years) using a 99-item food frequency questionnaire.
Incident CVD (combined stroke, ischemic heart disease death, and nonfatal myocardial infarction).
During 8.6 years mean follow-up, there were 811 incident CVD events. After adjustment for age, sex, education, diabetes, ever smoking, pack-years of smoking, daily physical activity, exercise intensity, alcohol intake, and fruit and vegetable fiber consumption, cereal fiber consumption was inversely associated with incident CVD (P for trend =.02), with 21% lower risk (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62-0.99) in the highest quintile of intake, compared with the lowest quintile. In similar analyses, neither fruit fiber intake (P for trend =.98) nor vegetable fiber intake (P for trend =.95) were associated with incident CVD. When CVD events were separately evaluated, higher cereal fiber intake was associated with lower risk of total stroke and ischemic stroke and a trend toward lower risk of ischemic heart disease death. In a post hoc analysis, dark breads such as wheat, rye, or pumpernickel were associated with a lower risk of incident CVD (HR, 0.76; 95% CI, 0.64-0.90) rather than cereal fiber from other sources.
Cereal fiber consumption late in life is associated with lower risk of incident CVD, supporting recommendations for elderly individuals to increase consumption of dietary cereal fiber.
JAMA The Journal of the American Medical Association 05/2003; 289(13):1659-66. · 30.03 Impact Factor
