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Biomedical subjects

Alberto Ascherio

Publications and source records attributed to Alberto Ascherio.

At least 19 recordsLinked to original sources
PubMed2007

Alcohol consumption and risk for coronary heart disease among men with hypertension.

BACKGROUND: Heavy alcohol consumption increases risk for hypertension, which is in itself a strong risk factor for cardiovascular disease (CVD). However, data on the association between alcohol consumption and CVD among individuals with hypertension are scarce. OBJECTIVE: To assess whether alcohol consumption is inversely associated with CVD among men with hypertension. DESIGN: Prospective cohort study. SETTING: United States. PARTICIPANTS: 11,711 men with hypertension from the Health Professionals Follow-Up Study. MEASUREMENTS: Alcohol consumption was assessed every 4 years by using a food-frequency questionnaire. Incident cases of nonfatal myocardial infarction (MI), fatal coronary heart disease, and stroke were documented from 1986 to 2002. RESULTS: During follow-up, 653 patients with MI were documented. Compared with patients abstaining from alcohol, the hazard ratio for participants with MI consuming 0.1 to 4.9 grams of alcohol per day was 1.09 (95% CI, 0.86 to 1.37); consuming 5 to 9.9 grams of alcohol per day was 0.81 (CI, 0.60 to 1.08 g/d); consuming 10 to 14.9 grams of alcohol per day was 0.68 (CI, 0.51 to 0.91 g/d); consuming 15 to 29.9 grams of alcohol per day was 0.72 (CI, 0.54 to 0.97 g/d); consuming 30 to 49.9 grams of alcohol per day was 0.67 (CI, 0.48 to 0.94 g/d); and consuming 50 or more grams of alcohol per day was 0.41 (CI, 0.22 to 0.77 g/d) (P < 0.001 for trend). Associations were similar for fatal and nonfatal MI. Alcohol consumption was not associated with total death or death due to CVD. Risks for total and ischemic stroke for patients consuming 10 to 29.9 g of alcohol per day were 1.40 (CI, 0.93 to 2.12) and 1.55 (CI, 0.90 to 2.68) compared with that of abstainers. When corrected for measurement error in alcohol consumption, dietary variables, and body mass index, the hazard ratio for participants with MI per 12.5 grams per day increment of alcohol intake was 0.68 (CI, 0.46 to 1.00). LIMITATIONS: Hypertension, alcohol consumption, and CVD risk factors were assessed by self-report. Available data used to correct for measurement error were primarily restricted to dietary variables. CONCLUSIONS: In this population of men with hypertension, moderate alcohol consumption was associated with a decreased risk for MI but not with risks for total death or death due to CVD. As in the general population, men with hypertension who drink moderately and safely may not need to change their drinking habits.

Adult↗
PubMed2006

Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.

CONTEXT: Epidemiological and experimental evidence suggests that high levels of vitamin D, a potent immunomodulator, may decrease the risk of multiple sclerosis. There are no prospective studies addressing this hypothesis. OBJECTIVE: To examine whether levels of 25-hydroxyvitamin D are associated with risk of multiple sclerosis. DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested case-control study among more than 7 million US military personnel who have serum samples stored in the Department of Defense Serum Repository. Multiple sclerosis cases were identified through Army and Navy physical disability databases for 1992 through 2004, and diagnoses were confirmed by medical record review. Each case (n = 257) was matched to 2 controls by age, sex, race/ethnicity, and dates of blood collection. Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples collected before the date of initial multiple sclerosis symptoms. MAIN OUTCOME MEASURES: Odds ratios of multiple sclerosis associated with continuous or categorical levels (quantiles or a priori-defined categories) of serum 25-hydroxyvitamin D within each racial/ethnic group. RESULTS: Among whites (148 cases, 296 controls), the risk of multiple sclerosis significantly decreased with increasing levels of 25-hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles). Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95% confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who had lower 25-hydroxyvitamin D levels than whites, no significant associations between vitamin D and multiple sclerosis risk were found. CONCLUSION: The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis.

Adolescent↗
PubMed2006

Trans fatty acids and blood lipids.

Intake of trans-unsaturated fatty acids (TFA) has been consistently shown in multiple and rigorous randomized trials to have adverse effects on blood lipids, most notably on the LDL:HDL cholesterol ratio, which is a strong marker of cardiovascular risk. When a mixture of TFA isomers obtained by partial hydrogenation of vegetable oils is used to replace oleic acid, there is a dose-dependent increase in the LDL:HDL ratio. The relationship between amount of TFA as % of energy and the increase in the LDL:HDL ratio appears to be approximately linear, with no evidence of a threshold at low levels of intake, and with slope twice as steep as that observed by replacing oleic with saturated fats. The average impact of TFA induced changes in the LDL:HDL ratio correspond to tens of thousands premature deaths in the US alone. Although dramatic, this effect is substantially smaller than the increase in cardiovascular mortality associated with TFA intake in epidemiological studies, suggesting that other mechanisms are likely to contribute to the toxicity of TFA.

Cholesterol, HDL↗
PubMed2006

Epstein-Barr virus and multiple sclerosis: evidence of association from a prospective study with long-term follow-up.

OBJECTIVE: To determine whether serum titers of anti-Epstein-Barr virus (EBV) antibodies are elevated in blood specimens collected up to 30 years prior to onset of multiple sclerosis (MS). METHODS: Individuals with MS were identified among members of the Kaiser Permanente Northern California health plan who participated in the multiphasic examinations administered between 1965 and 1974. Stored serum samples were used to compare anti-EBV antibody titers in 42 individuals who developed MS with age-matched and sex-matched controls. RESULTS: The geometric mean titers of antibodies to the Epstein-Barr nuclear antigen (EBNA) complex and its component EBNA-1 were significantly higher in the MS cases when compared with matched controls. The relative risk of MS associated with a 4-fold increase in antibody titers was 2.1 (95% confidence interval, 1.1-3.8) for the EBNA complex and 1.8 (95% confidence interval, 1.1-2.9) for EBNA-1. Elevations of antibody titers to the EBNA complex and EBNA-1 among MS cases first occurred between 15 to 20 years before the onset of symptoms and persisted thereafter. CONCLUSION: The elevation of anti-EBV titers is probably an early event in the pathogenesis of MS and is unlikely to be the result of an aspecific immune dysregulation.

Adult↗
PubMed2006

A prospective study of night shift work, sleep duration, and risk of Parkinson's disease.

The authors prospectively investigated whether working rotating night shifts was associated with the risk of Parkinson's disease among 84,794 female nurses who reported years of night shift work in 1988 (the US Nurses' Health Study). After 975,912 person-years of follow-up (1988-2000), 181 incident Parkinson's disease cases were documented. Compared with nurses who never worked rotating night shifts, those with 15 years or more of night shift work had a 50% lower risk of Parkinson's disease after adjustment for age and smoking (95% confidence interval: 0.26, 0.97; p(trend) = 0.01). Sleep duration was positively associated with Parkinson's disease risk: The relative risk was 1.84 (95% confidence interval: 0.99, 3.42) when comparing nurses who reported 9 or more hours of sleep per day with those who slept 6 hours or less (p(trend) = 0.005). These data suggest that working night shifts may be protective against Parkinson's disease or that low tolerance for night shift work is an early marker of Parkinson's disease. Conversely, habitual longer sleep duration may be an earlier marker of Parkinson's disease. Because of the novelty and the exploratory nature of these findings, confirmation is needed.

Alcohol Drinking↗
PubMed2006

Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.

Epidemiological studies have strongly linked caffeine consumption with a reduced risk of developing Parkinson's disease (PD) in men. Interestingly, in women, this inverse association is present only in those who have not taken postmenopausal estrogens, suggesting an interaction between the influences of estrogen and caffeine use on the risk of PD. To explore a possible biological basis for this interaction, we systematically investigated how the neuroprotective effect of caffeine is influenced by gender, ovariectomy (OVX), and then exogenous estrogen in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. (1) Caffeine treatment produced a dose-dependent attenuation of MPTP-induced striatal dopamine loss in both young and retired breeder (RB) male, but not female, mice. (2) In female mice (both young and RB), caffeine was less potent or altogether ineffective as a neuroprotectant after sham surgery compared to OVX or after OVX plus estrogen replacement compared to OVX plus placebo treatment. (3) Estrogen treatment also prevented the protection of caffeine against dopamine loss in young male mice. (4) Consistent with the putative protective effect of estrogen, female and OVX plus estrogen mice were relatively resistant to MPTP toxicity compared to male and OVX plus placebo mice, respectively. (5) There was no overall difference in brain levels of caffeine and its metabolites between OVX plus placebo and OVX plus estrogen mice. Together, these results suggest that estrogen can occlude and thereby prevent the neuroprotective effect of caffeine in a model of PD neurodegeneration, supporting a biological basis for the interaction between estrogen and caffeine in modifying the risk of PD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis.

OBJECTIVE: To characterize the association between infectious mononucleosis (IM), a frequent clinical manifestation of primary Epstein-Barr virus infection after childhood, and the risk for multiple sclerosis (MS). METHODS: We conducted a systematic review and meta-analysis of case-control and cohort studies of IM and MS. RESULTS: The combined relative risk of MS after IM from 14 studies was 2.3 (95% confidence interval, 1.7-3.0; p < 10(-8)). Potential sources of heterogeneity (ie, study design, MS definition, and latitude) barely influenced our results. INTERPRETATION: We conclude that Epstein-Barr virus infection manifesting as IM in adolescents and young adults is a risk factor for MS.

Adolescent↗
PubMed2006

Pesticide exposure and risk for Parkinson's disease.

OBJECTIVE: Chronic, low-dose exposure to pesticides is suspected to increase the risk for Parkinson's disease (PD), but data are inconclusive. METHODS: We prospectively examined whether individuals exposed to pesticides have higher risk for PD than those not exposed. The study population comprised participants in the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation of US men and women initiated in 1992 by the American Cancer Society. Follow-up surveys were conducted in 1997, 1999, and 2001. The 143,325 individuals who returned the 2001 survey and did not have a diagnosis or symptoms of PD at baseline (1992) were included in the analyses. RESULTS: Exposure to pesticides was reported by 7,864 participants (5.7%), including 1,956 farmers, ranchers, or fishermen. Individuals exposed to pesticides had a 70% higher incidence of PD than those not exposed (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.3; p = 0.002). The relative risk for pesticide exposure was similar in farmers and nonfarmers. No relation was found between risk for PD and exposure to asbestos, chemical/acids/solvents, coal or stone dust, or eight other occupational exposures. INTERPRETATION: These data support the hypothesis that exposure to pesticides may increase risk for PD. Future studies should seek to identify the specific chemicals responsible for this association.

Aged↗
PubMed2006

Blood donations, iron stores, and risk of Parkinson's disease.

Iron overload and systemic iron stores may be important in the pathogenesis of Parkinson's disease (PD). We therefore examined the association between blood donations, which reduce body iron stores, and risk of PD in the Health Professionals Follow-Up Study, a large cohort investigation of U.S. men. Our hypothesis was that blood donation reduces the risk of PD by lowering systemic iron stores. Although the number of blood donations was inversely related to the ferritin levels in a subsample of the study population, no association was found between the number of blood donations and risk of PD (P for trend = 0.6). Unexpectedly, the risk of PD was higher among men who reported recent multiple blood donations (P for trend = 0.05). The results of this study do not support the hypothesis that reduced systemic iron stores lower the risk of PD.

Adult↗
PubMed2006

Survival of Parkinson's disease patients in a large prospective cohort of male health professionals.

Parkinson's disease (PD) patients have higher mortality than individuals without PD. However, most of the previous studies were based on prevalent cases and few examined the potential effects of duration and smoking on the survival of PD patients. We compared the survival experience of 288 men with incident PD diagnosed between 1986 and 2000 with that of 51,012 men free of PD in the Health Professionals Follow-up Study. As of January 2002, 92 deaths occurred among PD cases and 8,485 among men without PD. After controlling for age, men with PD had 60% higher mortality than those without PD (95% CI: 1.3-2.0). PD mortality was strongly related to disease duration: compared with men without PD, the age-adjusted relative risk for PD patients was 1.1 during the first 5 years from diagnosis, 2.3 from 5 to 10 years, and 3.5 after 10 years (P < 0.0001 for trend). As expected, cigarette smoking was strongly and positively associated with total mortality among men free of PD (comparing >30 pack-years vs. never smokers, relative risk, 2.0; P < 0.0001 for trend), but this association was not observed among PD patients (RR: 1.0; P = 0.95 for trend). This study confirms that PD patients have a higher mortality than individuals without PD and that the excess mortality increases with disease duration. However, smoking seems to impose little additional risk among PD patients in this large cohort of health professionals.

Age Factors↗
PubMed2006

Soluble intercellular adhesion molecules, soluble vascular cell adhesion molecules, and risk of coronary heart disease.

OBJECTIVE: We examined the association of circulating levels of soluble intercellular adhesion molecules (sICAM-1) and soluble vascular cell adhesion molecules (sVCAM-1) with coronary heart disease (CHD) risk factors and whether the adhesion molecules alone, and in combination, can serve as predictors of coronary CHD. RESEARCH METHODS AND PROCEDURES: Among 18,225 men from the Health Professional Follow-up Study who provided blood in 1994, we documented 266 incidents of non-fatal myocardial infarction or fatal CHD during 6 years of follow-up. The cases were matched 1:2 with non-cases on age, smoking, and month of blood draw. We found both adhesion molecules directly associated with BMI, inflammatory biomarkers, and triglycerides and inversely associated with high-density lipoprotein and alcohol intake (p < 0.05). After adjustment for C-reactive protein, cholesterol-to-high-density lipoprotein ratio, age, smoking, BMI, physical activity, alcohol intake, history of diabetes, parental history of CHD, aspirin use, antihypertensive drug use, and fasting status, the relative risk of CHD was 1.69 [95% confidence interval (CI), 1.14 to 2.51] for sICAM-1 and 1.34 (95% CI, 0.91 to 1.96) for sVCAM-1, when comparing the top quintile with the lower four quintiles. Control for other inflammatory or lipid biomarkers did not appreciably attenuate the associations. When we cross-classified participants based on their sICAM-1 and sVCAM-1 levels, only the men in the top quintile of both biomarkers [relative risk = 2.39 (95% CI, 1.45 to 3.91)] had a significantly elevated risk of CHD (P interaction = 0.01, multivariate model). DISCUSSION: sICAM-1 and sVCAM-1 are directly associated with obesity and other CHD risk factors. The combination of high levels of both adhesion molecules might be associated with the development of CHD, independent of other CHD risk factors.

Aged↗
PubMed2005

Temporal relationship between elevation of epstein-barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis.

CONTEXT: Infection with Epstein-Barr virus (EBV) has been associated with an increased risk of multiple sclerosis (MS), but the temporal relationship remains unclear. OBJECTIVE: To determine whether antibodies to EBV are elevated before the onset of MS. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study conducted among more than 3 million US military personnel with blood samples collected between 1988 and 2000 and stored in the Department of Defense Serum Repository. Cases were identified as individuals granted temporary or permanent disability because of MS. For each case (n = 83), 2 controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected. Serial samples collected before the onset of symptoms were available for 69 matched case-control sets. MAIN OUTCOME MEASURES: Antibodies including IgA against EBV viral capsid antigen (VCA), and IgG against VCA, nuclear antigens (EBNA complex, EBNA-1, and EBNA-2), diffuse and restricted early antigens, and cytomegalovirus. RESULTS: The average time between blood collection and MS onset was 4 years (range, <1-11 years). The strongest predictors of MS were serum levels of IgG antibodies to EBNA complex or EBNA-1. Among individuals who developed MS, serum antibody titers to EBNA complex were similar to those of controls before the age of 20 years (geometric mean titers: cases = 245, controls = 265), but 2- to 3-fold higher at age 25 years and older (cases = 684, controls = 282; P<.001). The risk of MS increased with these antibody titers; the relative risk (RR) in persons with EBNA complex titers of at least 1280 compared with those with titers less than 80 was 9.4 (95% confidence interval [CI], 2.5-35.4; P for trend <.001). In longitudinal analyses, a 4-fold increase in anti-EBNA complex or anti-EBNA-1 titers during the follow-up was associated with a 3-fold increase in MS risk (EBNA complex: RR , 3.0; 95% CI, 1.3-6.5; EBNA-1: RR, 3.0; 95% CI, 1.2-7.3). No association was found between cytomegalovirus antibodies and MS. CONCLUSION: These results suggest an age-dependent relationship between EBV infection and development of MS.

Adult↗
PubMed2005

Cigarette smoking and the progression of multiple sclerosis.

An increased risk of multiple sclerosis among smokers has been found in several prospective epidemiological studies. The association between smoking and progression of multiple sclerosis has not been examined. We identified patients who had a first multiple sclerosis diagnosis recorded in the General Practice Research Database (GPRD) between January 1993 and December 2000. Their diagnosis and date of first symptoms were confirmed through examination of medical records. Smoking status was obtained from the computer records. To assess the association between smoking and risk of multiple sclerosis, we conducted a case-control study nested in the GPRD. Up to 10 controls per case were randomly selected, matched on age, sex, practice, date of joining the practice and availability of smoking data. To assess the association between smoking and progression of multiple sclerosis, we conducted a cohort study of multiple sclerosis cases with a relapsing-remitting onset. Our nested case-control study included 201 cases of multiple sclerosis and 1913 controls. The odds ratio [95% confidence interval (CI)] of multiple sclerosis was 1.3 (1.0-1.7) for ever smokers compared with never smokers. Our cohort study included 179 cases with a mean (median) length of follow-up of 5.3 (5.3) years. The hazard ratio of secondary progression was 3.6 (95% CI 1.3-9.9) for ever smokers compared with never smokers. These results support the hypothesis that cigarette smoking is associated with an increased risk of multiple sclerosis, and suggest that smoking may be a risk factor for transforming a relapsing-remitting clinical course into a secondary progressive course.

Adult↗
PubMed2005

Alcohol and risk for ischemic stroke in men: the role of drinking patterns and usual beverage.

BACKGROUND: The association of light to moderate alcohol consumption with risk for ischemic stroke remains controversial, as do the roles of beverage type and drinking pattern. OBJECTIVE: To assess the association of drinking patterns and beverage type with risk for ischemic stroke among men. DESIGN: Prospective cohort study. SETTING: United States. PARTICIPANTS: 38 156 male health professionals who were free of known cardiovascular disease or cancer at baseline in 1986. MEASUREMENTS: With a semi-quantitative food-frequency questionnaire, the authors individually ascertained consumption of regular and light beer, red and white wine, and liquor every 4 years. Alcohol consumption was categorized as light (0.1 to 9.9 g/d, or <1 drink daily), moderate (10.0 to 29.9 g/d, or 1 to 2 drinks daily), and heavier (> or =30.0 g/d, or > or =3 drinks daily). RESULTS: During a follow-up period of 14 years, 412 cases of incident ischemic stroke were documented. Compared with abstainers, light drinkers had a multivariate-adjusted relative risk of 0.99 (95% CI, 0.72 to 1.37), moderate drinkers had a multivariate-adjusted relative risk of 1.26 (CI, 0.90 to 1.76), and heavier drinkers had a multivariate-adjusted relative risk of 1.42 (CI, 0.97 to 2.09; P = 0.01 for trend). Consumption of 10.0 to 29.9 g of alcohol per day on 3 to 4 days per week appeared to be associated with the lowest risk (relative risk, 0.68 [CI, 0.44 to 1.05]). Red wine consumption was inversely associated with risk in a graded manner (P = 0.02 for trend), but other beverages were not. The apparently higher risk for ischemic stroke with heavier alcohol use appeared to be most pronounced for the embolic subtype. LIMITATIONS: This study had limited power to examine specific drinking patterns and heavy drinking and could not assess risk for hemorrhagic stroke. CONCLUSIONS: In this sample of male health professionals, light and moderate average alcohol use was generally not associated with an increased risk for ischemic stroke, although drinking pattern and beverage type modified this relation. Intake of more than 2 drinks per day may be associated with a higher risk for ischemic stroke.

Adult↗
PubMed2005

Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men.

BACKGROUND: Consumption of polyunsaturated fatty acids (PUFAs) may reduce coronary heart disease (CHD) risk, but n-6 PUFAs may compete with n-3 PUFA metabolism and attenuate benefits. Additionally, seafood-based, long-chain n-3 PUFAs may modify the effects of plant-based, intermediate-chain n-3 PUFAs. However, the interactions of these PUFAs in relation to CHD risk are not well established. METHODS AND RESULTS: Among 45,722 men free of known cardiovascular disease in 1986, usual dietary intake was assessed at baseline and every 4 years by using validated food-frequency questionnaires. CHD incidence was prospectively ascertained. Over 14 years of follow-up, participants experienced 218 sudden deaths, 1521 nonfatal myocardial infarctions (MIs), and 2306 total CHD events (combined sudden death, other CHD deaths, and nonfatal MI). In multivariate-adjusted analyses, both long-chain and intermediate-chain n-3 PUFA intakes were associated with lower CHD risk, without modification by n-6 PUFA intake. For example, men with > or = median long-chain n-3 PUFA intake (> or =250 mg/d) had a reduced risk of sudden death whether n-6 PUFA intake was below (<11.2 g/d; hazard ratio [HR]=0.52; 95% confidence interval [CI]=0.34 to 0.79) or above (> or =11.2 g/d; HR=0.60; 95% CI=0.39 to 0.93) the median compared with men with a < median intake of both. In similar analyses, > or = median intake of intermediate-chain n-3 PUFAs (> or =1080 mg/d) was associated with a reduced total CHD risk whether n-6 PUFA intake was lower (HR=0.88; 95% CI=0.78 to 0.99) or higher (HR=0.89; 95% CI=0.79 to 0.99) compared with a < median intake of both. Intermediate-chain n-3 PUFAs were particularly associated with CHD risk when long-chain n-3 PUFA intake was very low (<100 mg/d); among these men, each 1 g/d of intermediate-chain n-3 PUFA intake was associated with an approximately 50% lower risk of nonfatal MI (HR=0.42; 95% CI=0.23 to 0.75) and total CHD (HR=0.53; 95% CI=0.34 to 0.83). CONCLUSIONS: n-3 PUFAs from both seafood and plant sources may reduce CHD risk, with little apparent influence from background n-6 PUFA intake. Plant-based n-3 PUFAs may particularly reduce CHD risk when seafood-based n-3 PUFA intake is low, which has implications for populations with low consumption or availability of fatty fish.

Adult↗