Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians.

OBJECTIVE: To examine the development of age-related maculopathy (ARM) in a large-scale trial of low-dose aspirin treatment. METHODS: The Physicians' Health Study I was a randomized, double-masked, placebo-controlled trial of low-dose aspirin (325 mg every other day) and beta carotene (50 mg every other day) in the prevention of cardiovascular disease and cancer conducted among 22 071 US male physicians aged 40 to 84 years in 1982. A total of 21 216 participants did not report ARM at baseline, were followed up for at least 7 years, and are included in this analysis. MAIN OUTCOME MEASURES: Total ARM, defined as a self-report confirmed by medical record evidence of an initial diagnosis subsequent to randomization, and ARM with vision loss, defined as total ARM but with vision loss to 20/30 or worse attributable to ARM. RESULTS: Early termination of the randomized aspirin component of the Physicians' Health Study I, after an average of 60.2 months of treatment and follow-up due to a statistically extreme 44% reduced risk of first myocardial infarction, resulted in a far lower number of incident cases of ARM during the aspirin treatment period than would have accrued without early termination. Thus, during an average of 60.2 months of follow-up, a total of 117 cases of ARM were confirmed, including 57 cases responsible for vision loss to 20/30 or worse. There were 51 cases of ARM in the aspirin group and 66 in the placebo group (relative risk, 0.77; 95% confidence interval, 0.54-1.11). For ARM with vision loss, there were 25 cases in the aspirin group and 32 in the placebo group (relative risk, 0.78; 95% confidence interval, 0.46-1.32). CONCLUSIONS: These randomized trial data tend to exclude any large beneficial effect of 5 years of low-dose aspirin treatment on ARM. However, a smaller, but potentially important, beneficial effect cannot be ruled out and would require testing in randomized trials of adequate size and duration.

A prospective study of Helicobacter pylori seropositivity and the risk for future myocardial infarction among socioeconomically similar U.S. men.

BACKGROUND: The role of Helicobacter pylori as a determinant of cardiovascular disease is controversial. OBJECTIVE: To determine whether previous exposure to H. pylori is associated with an increased risk for myocardial infarction. DESIGN: Prospective case-control study. SETTING: Physicians' Health Study. PARTICIPANTS: Initially healthy U.S. men. MEASUREMENTS: Titers of IgG antibody against H. pylori and several inflammatory markers were measured in baseline blood samples obtained from 445 men who subsequently had a myocardial infarction (case-patients) and 445 men matched for age and smoking status who remained free of vascular disease (controls) during a mean follow-up of 8.9 years. RESULTS: Baseline seropositivity was similar among case-patients and controls (43.4% vs. 44.3%; rate ratio, 0.96 [95% CI, 0.7 to 1.3]). Minimal evidence of association was found between magnitude of seropositivity and subsequent risk and between seropositivity and levels of the inflammatory biomarkers. CONCLUSION: In a socioeconomically homogeneous population, we found limited evidence of association between H. pylori exposure and risk for future myocardial infarction.

Low-dose aspirin for migraine prophylaxis in women.

Although migraine is more common among women than men, the only two large, randomized trials of low-dose aspirin for migraine prophylaxis have been conducted in men. As part of the Women's Health Study, an ongoing randomized trial of low-dose aspirin and vitamin E among 39 876 female health professionals aged 45 and older, 1001 women with frequent migraine attacks were assigned to 100 mg of aspirin every other day (n = 525) or aspirin placebo (n = 476). Migraine frequency, as well as severity, duration, and degree of incapacitation, were assessed by self-report on questionnaires 12 months and 36 months after randomization, and also by monthly diaries kept before and after randomization. Women assigned to aspirin reported small and consistent decreases in migraine frequency (59.6% vs. 56.4% assigned to placebo reporting improvement at 36 months; odds ratio 1.13, 95% confidence interval, 0.86--1.48), as well as decreases in severity, duration, and migraine-related incapacitation. These reductions were not, however, statistically significant. These data are compatible with a small treatment effect of low-dose aspirin in the prophylaxis of migraine among middle-aged women.

Current perspectives on lipid lowering with statins to decrease risk of cardiovascular disease.

Although guidelines for individual risk factors for cardiovascular disease (CVD) assist the healthcare provider, management of the global risk profile of patients is the optimal means to minimize risk. Regardless of whether patients have one or more risk factors, elevated lipid values are generally considered to be a major contributor to global CVD risk. Therefore, reduction of lipid levels is one of the most effective methods to reduce risk of CVD. The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor class of drugs (also known as statins) has documented clinical benefits for reducing the incidence of myocardial infarction, stroke, death from CVD, and total death. Despite widespread acknowledgment of the very favorable benefit-to-risk ratio of the statins, most at-risk patients either are not being treated or are not at the goals defined by the National Cholesterol Education Program.

Serologic evaluations of women exposed to breast implants.

OBJECTIVE: There continues to be uncertainty whether women with silicone breast implants experience activation of their immune system and show increased prevalence of serologic markers of connective tissue diseases. We conducted laboratory tests in a large number of women with and without breast implants, and in diabetic patients with presumed silicone exposure via insulin syringes. METHODS: Subjects were chosen from women enrolled in the run-in phase of the Women's Health Study (WHS, a randomized trial testing aspirin and vitamin E in preventing cardiovascular disease and cancer), and included 298 women without breast implants, 298 women with breast implants, and 52 diabetic patients diagnosed before age 30. Comparison groups were matched on age, race, date of blood provided to the WHS, and randomization status. We compared the proportion with abnormal results in 16 serologic tests among the 3 groups of women, stratifying by the matching factors. We also tested for monoclonal immunoglobulins by electrophoresis. RESULTS: For 14 of the 16 serologic tests, the proportions with abnormal results among the 3 groups of women were not significantly different. Of the remaining tests, C3 levels were decreased in 8 (2.7%) women without breast implants and 22 (7.4%) women with breast implants (p = 0.003). C4 levels were decreased in 31 (10.4%) women without breast implants and 48 (16.1%) women with breast implants (p = 0.03). Women without breast implants and diabetic patients did not differ significantly in the proportions having decreased C3 and C4 levels. Women with breast implants did not have higher frequency of monoclonal immunoglobulins detected by electrophoresis. CONCLUSION: We found little evidence for activation of the immune system in women with breast implants. The clinical significance of isolated reductions in C3 and C4 levels, in the absence of other abnormalities such as elevated levels of antinuclear antibody, is unknown.

Time urgency and risk of non-fatal myocardial infarction.

BACKGROUND: Inconsistencies in the literature linking Type A behaviour pattern (TAB) to coronary heart disease (CHD) may be due to differences in the effects of various components of TAB, namely aggressiveness, hostility, ambitiousness, competitive drive, and a chronic sense of time urgency. METHODS: We investigated the association between sense of time urgency/impatience and non-fatal myocardial infarction (MI) in a study of 340 cases and an equal number of age-, sex-, and community-matched controls. RESULTS: A dose-response relation was apparent among subjects who rated themselves higher on the four-item time urgency/impatience scale (P-value for trend <0.001), with a matched odds ratio (OR) for non-fatal MI of 4.45 (95% CI : 2.20-8.99) comparing those with the highest rating to those with the lowest. After further adjustment for family history of premature MI, physical activity, body mass index, occupation, cigarette smoking, total caloric intake, per cent calories from saturated fat, alcohol intake, lipid levels, treated hypertension and diabetes, the dose-response relation remained (P-value for trend = 0.015) and the adjusted OR for MI was 3.99 (95% CI : 1.32-12.0) comparing those with the highest rating to those with the lowest. CONCLUSION: In these data, a sense of time urgency/impatience was associated with a dose-response increase in risk of non-fatal MI, independent of other risk factors. Prospective cohort studies of time urgency/impatience and incident CHD events are needed to confirm or refute these observations from a case-control study.

Active and passive smoking and risk of colds in women.

PURPOSE: To evaluate the association between active and passive smoking and frequency of colds in women. METHODS: Data on cigarette smoking and frequency and duration of colds were analyzed in the Women's Health Study (WHS), a randomized, double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals. RESULTS: After adjustment for age, body-mass index, prevalence of asthma and chronic lung diseases, alcohol intake, physical activity, and multivitamin use, current heavy smokers had no appreciable increase in the frequency of colds (relative risk (RR) for >or= 3 versus no colds in the past year, 1.05; 95% confidence interval (CI), 0.80-1.39), but a significantly increased risk of prolonged colds (RR for colds of > 7 vs. 1-3 days, 2.53; 95% CI, 1.95-3.29). There was no difference in the number of days confined to home. Nonsmoking women passively exposed to cigarette smoke had a slightly increased risk of both more frequent colds (RR, 1.33; 95% CI, 1.18-1.51) and more prolonged colds during the previous year (RR, 1.12; 95% CI, 0.99-1.27). CONCLUSIONS: Women who are currently heavy smokers are at increased risk of having colds with longer duration compared with nonsmokers. Nonsmoking women passively exposed to cigarette smoking are at slightly increased risk of having more frequent and longer colds than nonsmoking women not exposed to passive smoke.

Prospective study of cataract extraction and risk of coronary heart disease in women.

Oxidative damage to proteins in the human lens is believed to be important in the etiology of age-related cataract. Because free radical-mediated oxidative damage to lipoproteins may accelerate atherosclerosis, the authors hypothesized that the development of cataract might be a marker for such damage and therefore might be associated with future risk of coronary heart disease (CHD). The authors followed 60,657 women aged 45--63 years and without known coronary disease, stroke, or cancer in 1984. During 10 years of follow-up (674,283 person-years), the authors documented 887 incident cases of CHD and 2,322 deaths. After adjustment for age, smoking, and other coronary risk factors, cataract extraction was significantly associated with higher risk of CHD (relative risk (RR) = 1.88, 95% confidence interval (CI): 1.41, 2.50) for total CHD, 2.44 (95% CI: 1.54, 3.89) for fatal CHD, and 1.63 (95% CI: 1.14, 2.34) for nonfatal myocardial infarction). The positive association between cataract extraction and total CHD was stronger among women with a history of diabetes (RR = 2.80, 95% CI: 1.77, 4.42) than among those without reported diabetes (RR = 1.51, 95 percent CI: 1.04, 2.18). In multivariate analyses, cataract extraction was associated with significantly increased overall mortality (RR = 1.37, 95 percent CI: 1.13, 1.66), which was entirely explained by the increased mortality from cardiovascular disease (RR = 1.84, 95% CI: 1.29, 2.64). These findings are compatible with current hypotheses relating oxidative damage and tissue aging to the development of cataract and CHD.

Aspirin use and risk of cataract in posttrial follow-up of Physicians' Health Study I.

BACKGROUND: In Physicians' Health Study I, randomized trial results indicated no major beneficial effect of 5 years of low-dose aspirin treatment on total cataract (relative risk [RR], 0.94; 95% confidence interval [CI], 0.79-1.13) or cataract extraction (RR, 0.81; 95% CI, 0.65-1.01) during the period of treatment. OBJECTIVE: To examine the effect of assigned aspirin treatment and posttrial, self-selected aspirin use on the risk of age-related cataract over the 15 years of follow-up of Physicians' Health Study I. METHODS: Participants were 20 968 US male physicians enrolled in Physicians' Health Study I who did not report cataract at baseline. At 7 years, after termination of the randomized aspirin component of the trial, self-selected aspirin use was computed from annual questionnaires. The main outcome measures were age-related cataract and extraction of age-related cataract, defined as an incident, age-related lens opacity responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review. RESULTS: During a median of 14.9 years of follow-up, there were 2081 cataracts and 1198 cataract extractions. Overall, the age- and beta carotene-adjusted RR of cataract in men assigned to aspirin compared with those assigned to placebo was 1.09 (95% CI, 1.00-1.18). For cataract extraction, the RR was 1.09 (95% CI, 0.98-1.22). During a median posttrial follow-up of 7.9 years, a total of 1225 incident cataracts and 635 cataract extractions were documented. The multivariate RR of cataract in men who reported using aspirin frequently (>/=180 days per year) at 7 years compared with nonusers (0-13 days per year) was 1.20 (95% CI, 1.03-1.40). For cataract extraction, the multivariate RR was 1.22 (95% CI, 0.98-1.51). Results for diagnosis and extraction of cataract subtypes were similar. CONCLUSIONS: Analyses based on randomized aspirin assignment indicated no long-term benefit of 5 years of low-dose aspirin treatment on total cataract or cataract extraction. Posttrial, observational data also indicated no decreased risk of cataract in aspirin users and suggested a small increased risk of cataract in aspirin users. Further randomized trial data to investigate the effect of longer term treatment with low-dose aspirin are being collected as part of the ongoing Women's Health Study, a randomized trial of low-dose aspirin and vitamin E among 39 876 apparently healthy, postmenopausal US female health professionals.

Physical activity and breast cancer risk: the Women's Health Study (United States).

OBJECTIVE: It is biologically plausible for physical activity to decrease breast cancer risk; however, epidemiologic studies have yielded inconsistent findings. We therefore examined physical activity and breast cancer risk in the Women's Health Study. METHODS: We assessed physical activity among 39,322 apparently healthy women, aged > or = 45 years, and prospectively followed them for an average of 48 months. Four hundred eleven women developed breast cancer, with 222 positive for both estrogen and progesterone receptors. RESULTS: Among all women the multivariate relative risks of all breast cancer associated with < 840, 840-2519, 2520-6299, and > or = 6300 kJ/week expended on recreational activities and stair climbing were 1.00 (referent), 1.04 (95% confidence interval, 0.77-1.40), 0.86 (0.64-1.17), and 0.80 (0.58-1.12), respectively; p-trend = 0.11. However, among postmenopausal women there was a significant inverse trend for all breast cancer; the corresponding relative risks were 1.0 (referent), 0.97 (0.68-1.4), 0.78 (0.54-1.1), and 0.67 (0.44-1.0), respectively; p-trend = 0.03. Physical activity was unrelated to breast cancers positive for both estrogen and progesterone receptors either among all or postmenopausal women (p-trend = 0.50 and 0.26, respectively). When we assessed only vigorous recreational activity, requiring > or = 6 METs or multiples of resting metabolic rate, we observed no significant associations with all or steroid hormone receptor positive breast cancer, either among all or postmenospausal women. CONCLUSIONS: These data suggest that physical activity during middle age and older is not uniformly associated with decreased breast cancer risk. Among postmenopausal women only, higher levels of physical activity may decrease the risk of breast cancer. This study, however, had limited statistical power to detect small effects.

Influence of a methionine synthase (D919G) polymorphism on plasma homocysteine and folate levels and relation to risk of myocardial infarction.

Methionine synthase (MS) encodes an enzyme that catalyzes the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetrahydrofolate, which is the major circulating form of folate in the body. Functional genetic variants of the MS may alter total homocysteine (tHcy) as well as folate levels which are independent risk factors for vascular disease. The influence of a common genetic polymorphism (2756A-->G, D919G) of the MS gene on plasma tHcy and folate levels and its relation to the risk of myocardial infarction (MI) in a prospective study of male physicians in the US was investigated. A nested case-control study was conducted within the Physicians' Health Study which was originally designed as a double-blind trial of aspirin and beta-carotene among 22071 US male physicians, aged 40-84 years in 1982. Sixty-eight percent of participants also donated a blood sample. The study included 387 incident MI case and 767 controls matched on age, smoking status, and time from randomization in 6-month intervals. Individuals with GG genotype had a non-significant reduction of MI risk (RR 0.51, 95% CI 0.17-1.16) compared to individuals with DD genotype after adjusting for MI risk factors. The MS polymorphism was associated with decreased tHcy (10.55, 9.87 and 9.57 nmol/ml for DD, DG and GG genotypes, respectively) and increased folate levels (3.95, 3.78, 7.31 ng/ml for DD, DG and GG genotypes, respectively) only among controls but not cases. It was concluded that influence of the MS (D919G) polymorphism on the plasma tHcy and folate levels is at most moderate, but should be further investigated in other large prospective studies.

A prospective evaluation of the CD14 C(-260)T gene polymorphism and the risk of myocardial infarction.

The T allele at position -260 of the CD14 lipopolysaccharide receptor gene (CD14) has recently been hypothesized to be a risk factor for myocardial infarction (MI). However, no prospective data relating this polymorphism to risk of future MI are available. In the physicians' health study (PHS), 14916 apparently healthy men were followed over a 12-year period for incident MI. Employing a nested case-control study design, the CD14 C(-260)T polymorphism was evaluated among 387 study participants who developed MI (cases) and among an equal number of age- and smoking-matched study participants who remained free of vascular diseases during follow-up (controls). All observed genotype frequencies were in Hardy-Weinberg equilibrium. However, the allele and genotype distributions of the CD14 polymorphism were similar among cases and controls, both in the total cohort and in all subgroups evaluated. Furthermore, no evidence of association was observed assuming additive, dominant, or recessive mode of inheritance. For example, the relative risk of future MI in a comparison of homozygous mutants to homozygous wild types was 1.00 (95% CI=0.7-1.5; P=0.9). In this large prospective study, the CD14 C(-260)T gene polymorphism was not associated with risks of future MI. Thus, in contrast to prior studies, these data indicate that screening for CD14 C(-260)T genotypes is unlikely to be a useful tool for risk assessment.

Prospective study of fat and protein intake and risk of intraparenchymal hemorrhage in women.

BACKGROUND: -Dietary animal fat and protein have been inversely associated with a risk of intraparenchymal hemorrhage in ecological studies. METHODS AND RESULTS: In 1980, 85 764 women in the Nurses' Health Study cohort, who were 34 to 59 years old and free of diagnosed cardiovascular disease and cancer, completed dietary questionnaires. From these questionnaires, we calculated fat and protein intake. By 1994, after 1.16 million person-years of follow-up, 690 incident strokes, including 74 intraparenchymal hemorrhages, had been documented. Multivariate-adjusted risk of intraparenchymal hemorrhage was higher among women in the lowest quintile of energy-adjusted saturated fat intake than at all higher levels of intake (relative risk [RR], 2.36; 95% CI, 1.10 to 5.09; P:=0.03). For trans unsaturated fat, the corresponding RR was 2.50 (95% CI, 1.35 to 4.65; P:=0.004). Animal protein intake was inversely associated with risk (RR in the highest versus lowest quintiles, 0.32; 95% CI, 0.10 to 1.00; P:=0.04). The excess risk associated with low saturated fat intake was observed primarily among women with a history of hypertension (RR, 3.66; 95% CI, 1.09 to 12.3; P=0.04), but such an interaction was not seen for trans unsaturated fat or animal protein. These nutrients were not related to risk of other stroke subtypes. Dietary cholesterol and monounsaturated and polyunsaturated fat were not related to risk of any stroke subtype. CONCLUSIONS: Low intake of saturated fat and animal protein was associated with an increased risk of intraparenchymal hemorrhage, which may help to explain the high rate of this stroke subtype in Asian countries. The increased risk with low intake of saturated fat and trans unsaturated fat is compatible with the reported association between low serum total cholesterol and risk.

Intake of fish and omega-3 fatty acids and risk of stroke in women.

CONTEXT: Some prospective studies have shown an inverse association between fish intake and risk of stroke, but none has examined the relationship of fish and omega-3 polyunsaturated fatty acid intake with risk of specific stroke subtypes. OBJECTIVE: To examine the association between fish and omega-3 polyunsaturated fatty acid intake and risk of stroke subtypes in women. DESIGN, SETTING, AND SUBJECTS: Prospective cohort study of women in the Nurses' Health Study cohort, aged 34 to 59 years in 1980, who were free from prior diagnosed cardiovascular disease, cancer, and history of diabetes and hypercholesterolemia and who completed a food frequency questionnaire including consumption of fish and other frequently eaten foods. The 79 839 women who met our eligibility criteria were followed up for 14 years. MAIN OUTCOME MEASURE: Relative risk of stroke in 1980-1994 compared by category of fish intake and quintile of omega-3 polyunsaturated fatty acid intake. RESULTS: After 1 086 261 person-years of follow-up, 574 incident strokes were documented, including 119 subarachnoid hemorrhages, 62 intraparenchymal hemorrhages, 303 ischemic strokes (264 thrombotic and 39 embolic infarctions), and 90 strokes of undetermined type. Among thrombotic infarctions, 90 large-artery occlusive infarctions and 142 lacunar infarctions were identified. Compared with women who ate fish less than once per month, those with higher intake of fish had a lower risk of total stroke: the multivariate relative risks (RRs), adjusted for age, smoking, and other cardiovascular risk factors, were 0.93 (95% confidence interval [CI], 0.65-1.34) for fish consumption 1 to 3 times per month, 0.78 (95% CI, 0.55-1.12) for once per week, 0.73 (95% CI, 0.47-1.14) for 2 to 4 times per week, and 0.48 (95% CI, 0.21-1.06) for 5 or more times per week (P for trend =.06). Among stroke subtypes, a significantly reduced risk of thrombotic infarction was found among women who ate fish 2 or more times per week (multivariate RR, 0.49; 95% CI, 0.26-0.93). Women in the highest quintile of intake of long-chain omega-3 polyunsaturated fatty acids had reduced risk of total stroke and thrombotic infarction, with multivariate RRs of 0.72 (95% CI, 0.53-0.99) and 0.67 (95% CI, 0.42-1.07), respectively. When stratified by aspirin use, fish and omega-3 polyunsaturated fatty acid intakes were inversely associated with risk of thrombotic infarction, primarily among women who did not regularly take aspirin. There was no association between fish or omega-3 polyunsaturated fatty acid intake and risk of hemorrhagic stroke. CONCLUSIONS: Our data indicate that higher consumption of fish and omega-3 polyunsaturated fatty acids is associated with a reduced risk of thrombotic infarction, primarily among women who do not take aspirin regularly, but is not related to risk of hemorrhagic stroke.

Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians.

OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men.

A prospective study of blood pressure and risk of cataract in men.

PURPOSE: Cataract is the leading cause of blindness worldwide. Blood pressure has been identified as a risk factor in some, but not all, previous studies. We aimed to test prospectively the hypothesis that high blood pressure increases risk of age-related cataract. METHODS: Participants in the Physicians' Health Study of 22,071 men aged 40 to 84 years in 1982 completed annual questionnaires that provided medical history including self-reported blood pressure, treatment for hypertension, and cataract. Over 12 years, 1392 cataracts were confirmed by medical record review among 17,762 physicians with complete data and no reported cataract at baseline. We used proportional hazards regression models to examine relations of systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension, as well as antihypertensive medications with cataract, after control for potential confounding factors. RESULTS: In models adjusting for age and randomized treatment assignment, there was a significant relationship of SBP, but not DBP, hypertension, or antihypertensive medications (each p > or = 0.23) with incident cataract. Estimates were attenuated after adjusting for multiple potential confounders, although the relationship of SBP with incident cataract remained significant. The multivariate adjusted rate ratio (95% confidence interval) of cataract for SBP > or = 150 versus < 120 mm Hg was 1.31 (1.04-1.66), p for trend = 0.04. For DBP > or = 90 versus < 70 mm Hg, the estimate was 1.11 (0.84-1.45), p for trend = 0.33. CONCLUSIONS: Overall, these data suggest that the relationship of blood pressure with cataract is not strong, and is subject to confounding by other risk factors. The modest magnitude of the association with SBP and lack of significant relationships with DBP and hypertension may suggest a non-causal relationship of blood pressure with cataract.

G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism.

OBJECTIVES: The study was done to determine whether the G20210A mutation in the prothrombin gene increases the risk of recurrent venous thromboembolism (VTE), both alone and in combination with factor V Leiden. BACKGROUND: Several inherited defects of coagulation are associated with increased risk of first VTE, including a recently identified G20210A mutation in the prothrombin gene. However, whether the presence of this mutation confers an increased risk of recurrent venous thromboembolism is controversial. METHODS: A total of 218 men with incident venous thromboembolism were genotyped for the prothrombin mutation and for factor V Leiden and were followed prospectively for recurrent VTE over a follow-up period of 7.3 years. RESULTS: A total of 29 men (13.3%) suffered recurrent VTE. Five of the 14 carriers of the prothrombin mutation developed recurrent VTE (35.7%; incidence rate = 8.70 per 100 person-years), while 24 of 204 individuals who did not carry the prothrombin mutation developed recurrent VTE (11.8%; incidence rate = 1.76 per 100 person-years). Thus, presence of the G20210A mutation was associated with an approximate fivefold increased risk for recurrent VTE (crude relative risk [RR] 4.93; 95% confidence interval [CI] 1.9-12.9; p = 0.001; age-, smoking-, and body mass index-adjusted RR 5.28; 95% CI 2.0-14.0; p = 0.001). In these data, recurrence rates were similar among those with an isolated mutation in the prothrombin gene (18.2%) as compared to those with an isolated factor V Leiden mutation (19.2%). However, all three study participants who carried both mutations (100%) suffered a recurrent event during follow-up. CONCLUSIONS: In a prospective evaluation of 218 men, the presence ofprothrombin mutation was associated with a significantly increased risk of recurrent VTE, particularly among those who co-inherited factor V Leiden.

Black-white inequalities in mortality and life expectancy, 1933-1999: implications for healthy people 2010.

OBJECTIVES: Optimistic predictions for the Healthy People 2010 goals of eliminating racial/ethnic disparities in health have been made based on absolute improvements in life expectancy and mortality. This study sought to determine whether there is evidence of relative improvement (a more valid measure of inequality) in life expectancy and mortality, and whether such improvement, if demonstrated, predicts future success in eliminating disparities. METHODS: Historical data from the National Center for Health Statistics and the Census Bureau were used to predict future trends in relative mortality and life expectancy, employing an Autoregressive Integrated Moving Average (ARIMA) model. Excess mortality and time lags in mortality and life expectancy for blacks relative to whites were also estimated. RESULTS: Based on data for 1945 to 1999, forecasts for relative black:white age-adjusted, all-cause mortality and white:black life expectancy at birth showed trends toward increasing disparities. From 1979, when the Healthy People initiative began, to 1998, the black:white ratio of age-adjusted, gender-specific mortality increased for all but one of nine causes of death that accounted for 83.4% of all US mortality in 1998. From 1980 to 1998, average numbers of excess deaths per day among American blacks relative to whites increased by 20%. American blacks experienced 4.3 to 4.5 million premature deaths relative to whites in 1940-1999. CONCLUSIONS: The rationale that underlies the optimistic Healthy People 2010 forecasts, that future success can be built on a foundation of past success, is not supported when relative measures of inequality are used. There has been no sustained decrease in black-white inequalities in age-adjusted mortality or life expectancy at birth at the national level since 1945. Without fundamental changes, most probably related to the ways medical and public health practitioners are trained, evaluated, and compensated for prevention-related activities, as well as further research on translating the findings of prevention studies into clinical practice, it is likely that simply reducing disparities in access to care and/or medical treatment will be insufficient. Millions of premature deaths will continue to occur among African Americans.

Relations of body fat distribution and height with cataract in men.

BACKGROUND: Cataract is the leading cause of blindness worldwide. Body mass index (BMI; in kg/m(2)) is a risk factor for cataract, but other anthropometric measurements may also be important. OBJECTIVE: We tested relations of alternative measures of body size, including height and waist-to-hip ratio (WHR), as well as BMI, with cataract. DESIGN: This was a prospective follow-up study. We analyzed data from 20271 participants in the Physicians' Health Study who did not have cataract at baseline and for whom there was complete information on weight, height, and other risk factors. For analyses concerning WHR, we excluded 3121 additional men for whom we did not have these measurements, assessed at the ninth year of follow-up. The main outcome measures were incident cataract and cataract surgery. RESULTS: Among the 17150 men for whom there were complete data, we confirmed an incident cataract in 1727 during an average of 14 y of follow-up. In proportional hazards regression models that adjusted for many known or suspected risk factors, higher BMI [rate ratio (RR) = 1.25 for >/=27.8 compared with <22, P: for trend = 0. 03], height (RR = 1.23 for >/=184 cm compared with