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J D Curb

Publications and source records attributed to J D Curb.

At least 19 recordsLinked to original sources
PubMed2007

Surrogate estimates of insulin sensitivity in subjects with hypertension.

The purpose of the study is to compare surrogate estimates of insulin sensitivity with a directly measured insulin sensitivity index, steady-state plasma glucose (SSPG) from insulin suppression test (IST), in subjects with hypertension. Two hundred and twenty-eight hypertensive patients who received IST for SSPG were included for analysis. Estimates from fasting measurements alone, homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)), and indices from fasting and/or 2 h samples (ISI(0,120) and ISI(TX)) were calculated. In addition to Pearson and partial correlations, variance-component models were used to test the relationship between surrogate estimates of insulin sensitivity and SSPG. A large proportion of variance owing to covariates in the variance-component models indicated the goodness of model fit, irrespective of the independence among variables. SSPG was positively correlated with logarithmic transformation (Log) (HOMA-IR) and negatively correlated with QUICKI, Log (ISI(0,120)) and ISI(TX) (all P<0.0001). Log (ISI(0,120)) seemed to have a better correlation with SSPG (r=-0.72) than other measures in partial correlation. The proportion of variance owing to all covariates of Log (ISI(0,120)) and ISI(TX) were larger than those of Log (HOMA-IR) and QUICKI in the variance-component models. After adjustments for demographic and obesity covariates, the proportion of variance explained by Log (ISI(0,120)) were largest among the surrogate measures in the variance-component models. Our results showed that ISI(0,120) and ISI(TX) correlated better with SSPG than those used fasting measures alone (HOMA-IR and QUICKI). Log (ISI(0,120)) currently showing the strongest association with SSPG than other estimates is adaptable for use in large studies of hypertension.

Adult↗
PubMed2005

Excessive daytime sleepiness and subsequent development of Parkinson disease.

OBJECTIVE: To determine if excessive daytime sleepiness (EDS) can predate future Parkinson disease (PD). METHODS: EDS was assessed in 3,078 men aged 71 to 93 years in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent PD and dementia. Follow-up for incident PD was based on three repeat neurologic assessments from 1994 to 2001. RESULTS: During the course of follow-up, 43 men developed PD (19.9/10,000 person-years). After age adjustment, there was more than a threefold excess in the risk of PD in men with EDS vs men without EDS (55.3 vs 17.0/10,000 person-years; odds ratio [OR] = 3.3; 95% CI = 1.4 to 7.0; p = 0.004). Additional adjustment for insomnia, cognitive function, depressed mood, midlife cigarette smoking and coffee drinking, and other factors failed to alter the association between EDS and PD (OR = 2.8; 95% CI = 1.1 to 6.4; p = 0.014). Other sleep related features such as insomnia, daytime napping, early morning grogginess, and frequent nocturnal awakening showed little relation with the risk of PD. CONCLUSIONS: Excessive daytime sleepiness may be associated with an increased risk of developing Parkinson disease.

Aged↗
PubMed2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗
PubMed2005

Consumption of milk and calcium in midlife and the future risk of Parkinson disease.

OBJECTIVE: To examine the relation between milk and calcium intake in midlife and the risk of Parkinson disease (PD). METHODS: Findings are based on dietary intake observed from 1965 to 1968 in 7,504 men ages 45 to 68 in the Honolulu Heart Program. Men were followed for 30 years for incident PD. RESULTS: In the course of follow-up, 128 developed PD (7.1/10,000 person-years). Age-adjusted incidence of PD increased with milk intake from 6.9/10,000 person-years in men who consumed no milk to 14.9/10,000 person-years in men who consumed >16 oz/day (p = 0.017). After further adjustment for dietary and other factors, there was a 2.3-fold excess of PD (95% CI 1.3 to 4.1) in the highest intake group (>16 oz/day) vs those who consumed no milk. The effect of milk consumption on PD was also independent of the intake of calcium. Calcium from dairy and nondairy sources had no apparent relation with the risk of PD. CONCLUSIONS: Findings suggest that milk intake is associated with an increased risk of Parkinson disease. Whether observed effects are mediated through nutrients other than calcium or through neurotoxic contaminants warrants further study.

Age of Onset↗
PubMed2004

A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly.

High density lipoprotein cholesterol (HDL-C) levels are inversely associated with the incidence of coronary heart disease (CHD) in middle-aged individuals; in the elderly, the association is less clear. Genetic factors, including variations in the cholesteryl ester transfer protein (CETP) gene, play a role in determining HDL-C levels. Controversy remains about whether CETP deficiency and the resultant rise in HDL-C are antiatherogenic, or whether CETP has the opposite effect due to its role in reverse cholesterol transport. In a seven-year follow-up of 2340 men aged 71-93 in the Honolulu Heart Program, the age-adjusted CHD incidence rates were significantly lower in men with high versus low HDL-C levels. After adjustment for age, hypertension, smoking, and total cholesterol, the relative risk of CHD for those with HDL-C levels >or=60 mg/dl, compared with those with HDL-C levels <40 mg/dl, was 0.6. Men with a CETP mutation had the lowest rates of CHD, although this was not statistically significant. These data indicate that HDL-C remains an important risk factor for CHD in the elderly. Whether a CETP mutation offers additional protection against CHD warrants further investigation.

Age Factors↗
PubMed2003

Genetic epistasis of adiponectin and PPARgamma2 genotypes in modulation of insulin sensitivity: a family-based association study.

AIMS/HYPOTHESIS: Genetic interactions in modulating the phenotypes of a complex trait, such as insulin sensitivity, were usually taken for granted. However, this has not been commonly shown. Previous studies have suggested that both PPARgamma2 and adiponectin genes could influence insulin sensitivity. Therefore it is likely that they could modulate insulin sensitivity through gene to gene interactions. METHODS: We genotyped 1793 subjects of Chinese and Japanese descendents from 601 hypertensive families recruited in Sapphire study for a T94G in the adiponectin gene exon 2 and the PPARgamma2 Pro12Ala polymorphisms. Serum insulin concentrations and insulin resistance index (HOMA(IR)) were used as the markers of insulin sensitivity. RESULTS: We found that the T allele of adiponectin gene was associated with a higher Ins60 and higher area under curve of insulin (AUCi) in OGTT utilizing all subjects in a mixed model that corrected for family effects. Important interactions between adiponectin and PPARgamma2 genotypes were found in fasting insulin concentrations (Ins0), insulin concentrations at 2-h (Ins120) in OGTT and insulin resistance index (HOMA(IR)). The main effects of the PPARgamma2 genotypes were in the plasma glucose concentrations in OGTT. In contrast, the main effects of adiponectin genotypes were in every insulin variable, including Ins0, Ins60, Ins120, AUCi and HOMA(IR). The subjects carrying the adiponectin G allele and the PPARgamma2 Ala12 allele seemed to be more insulin sensitive. CONCLUSION/INTERPRETATION: These results showed that adiponectin is a genetic factor associated with insulin sensitivity. Interactions with PPARgamma2 genotypes modified this association.

Adiponectin↗
PubMed2003

Differences in cardiovascular disease risk factors between Japanese in Japan and Japanese-Americans in Hawaii: the INTERLIPID study.

Despite increase in serum total cholesterol, high smoking rate, and frequency of adverse blood pressure levels in Japan, coronary heart disease (CHD) incidence and mortality apparently remain substantially lower at all ages in Japan than in the US and other Western societies. To better understand these differences, we compared CHD biomedical risk factors and dietary variables in Japanese living in Japan and 3rd and 4th generation Japanese emigrants living a primarily Western lifestyle in Hawaii, in an ancillary study of the INTERMAP. Men and women aged 40-59 years were examined by common standardized methods-four samples in Japan (574 men, 571 women) and a Japanese-American sample in Hawaii (136 men, 131 women). Average systolic (SBP) and diastolic (DBP) blood pressures were significantly higher in men in Japan than in Hawaii; there were no significant differences in women. The treatment rate of hypertension was much lower in Japan than Hawaii. Smoking prevalence was higher, markedly so for men, in Japan than Hawaii. Body mass index, serum total and low-density lipoprotein cholesterol, HbA1c, and fibrinogen were significantly lower in Japan than in Hawaii; high-density lipoprotein cholesterol was higher in Japan. Total fat, saturated fatty acid intake, and Keys dietary lipid score were lower in Japan than in Hawaii. Polyunsaturated/saturated fatty acid ratio and omega-3 fatty acid intake were higher in Japan than in Hawaii. In conclusion, levels of several, especially lipid, CHD risk factors were generally lower in Japanese in Japan than in Japanese in Hawaii. These differences were smaller for women than men between Japan and Hawaii. They may partly explain lower CHD incidence and mortality in Japan than Western industrialized countries.

Adult↗
PubMed2002

Midlife adiposity and the future risk of Parkinson's disease.

BACKGROUND: Evidence suggests that nigrostriatal system disorders are associated with PD and adiposity. Whether patterns of adiposity coexist or predate clinical PD is unknown. This report examines the relation between midlife adiposity and the risk of PD. METHODS: Measurement of adiposity occurred from 1965 to 1968 in 7,990 men in the Honolulu Heart Program (aged 45 to 68 years and without PD). Adiposity measures included body mass index (BMI), subscapular skinfold thickness (SSF), and triceps skinfold thickness (TSF). Follow-up for incident PD occurred over a 30-year period. RESULTS: During the course of follow-up, PD was observed in 137 men. Among the measures of adiposity, age-adjusted incidence of PD increased threefold from 3.7/10,000 person-years in the bottom quartile of TSF (1 to 5 mm) to 11.1/10,000 person-years in the top quartile (11 to 32 mm, p < 0.001). Effects of TSF on PD were independent of cigarette smoking, coffee consumption, physical activity, daily caloric and fat intake, and the other measures of adiposity (p < 0.001). Whereas rates of PD were lowest in the bottom quartile of BMI and SSF vs higher quartiles, associations with PD were weaker than they were for TSF. The effect of TSF on clinical onset before age 65 years was similar to the effect that was observed in later life. CONCLUSIONS: Increased triceps skinfold thickness measured in midlife is associated with an elevated risk of future PD. Whether patterns of adiposity reflect a unique metabolic pathology in individuals at a high risk of PD warrants further study.

Adipose Tissue↗
PubMed2002

Relationship between plasma glucose concentrations and Native Hawaiian Ancestry: The Native Hawaiian Health Research Project.

OBJECTIVE: To investigate the relationship between fasting glucose and 2 h glucose with percentage of Hawaiian ancestry and ethnic admixture. DESIGN: Cross-sectional epidemiological study of type 2 diabetes and heart disease risk factor prevalence among Native Hawaiians. SUBJECTS: A total of 578 Native Hawaiians residing in two rural communities were examined between 1993 and 1996. Sample sizes in statistical analyses varied due to missing data and selection criteria based on ethnic ancestry. MEASUREMENTS: Percentage of Hawaiian ancestry and non-Hawaiian ethnic admixture, assessed by self-report. Fasting and 2 h post glucose challenge plasma glucose levels. Anthropometric measures (height, weight, waist and hip circumferences). Self-report of diet and physical activity. Medical history. RESULTS: Increased Hawaiian blood quantum was significantly associated with increased fasting glucose (P=0.0047), increased body mass index (BMI; P<0.0001), waist-to-hip ratio (WHR; P=0.0103), and age (P<0.0001), but not with leisure time physical activity and total dietary caloric intake. This association was attenuated after adjusting for BMI and WHR, but not by age-adjustment alone. However, when the effects of descent from other ethnic groups was examined in a subset of participants, full-Hawaiians had significantly higher fasting glucose concentrations (7.28 mmol/l) than part-Hawaiians after adjustments for age, gender, BMI and WHR. In contrast, part-Hawaiians of predominantly Asian ancestry had the highest 2 h glucose concentrations (7.62 mmol/l). CONCLUSION: These results suggest that ethnic admixture may be an important, but extremely complex, factor concerning the high prevalence of type 2 diabetes observed among this population. The complexity of this relationship may have obscured the relationship between ancestry and glucose tolerance in earlier observations of this population.

Adult↗
PubMed2001

Cholesterol and neuropathologic markers of AD: a population-based autopsy study.

OBJECTIVE: To examine the association of plasma cholesterol (total and high-density [HDL] and low-density lipoprotein) levels with neuritic plaques (NP) and neurofibrillary tangles (NFT) in a population-based autopsy series of 218 Japanese American men followed as a part of the Honolulu-Asia Aging Study. METHODS: Cholesterol levels were measured in late life (average age at death 84.6 years) in all subjects (n = 218) and in midlife (20 years before late life) in a subsample (n = 89); for the analyses, levels were categorized into quintiles, with the lowest quintile serving as the reference. Tissue from four areas of neocortex and two areas of hippocampus was prepared with Bielschowsky silver-stained sections and evaluated by one of three neuropathologists who were blinded to clinical information. Diffuse and neuritic plaques and NFT were counted in field areas standardized to 1 mm(2). Fields were selected from areas with the highest numbers of lesions, and the field with the highest count was taken to represent the brain area. RESULTS: After adjusting for age at death, education, APOE allele, dementia, neuropathologic infarction, and blood pressure, a strong linear association was found for increasing late-life HDL cholesterol (HDL-C) levels and an increasing number of neocortical NP (5th versus 1st quintile: count ratio [95% CI] 2.30 [1.05 to 5.06]) and hippocampal (2.63 [1.25 to 5.50]) and neocortical (4.20 [1.73 to 10.16]) NFT. Trends were similar for the midlife HDL-C levels. CONCLUSIONS: The constituents of HDL-C may play a role in the formation of AD pathology, and these processes are reflected in peripheral measures.

Aged↗
PubMed2001

Frequency of bowel movements and the future risk of Parkinson's disease.

BACKGROUND: Constipation is frequent in PD, although its onset in relation to clinical PD has not been well described. Demonstration that constipation can precede clinical PD could provide important clues to understanding disease progression and etiology. The purpose of this report is to examine the association between the frequency of bowel movements and the future risk of PD. METHODS: Information on the frequency of bowel movements was collected from 1971 to 1974 in 6790 men aged 51 to 75 years without PD in the Honolulu Heart Program. Follow-up for incident PD occurred over a 24-year period. RESULTS: Ninety-six men developed PD an average of 12 years into follow-up. Age-adjusted incidence declined consistently from 18.9/10,000 person-years in men with <1 bowel movement/day to 3.8/10,000 person-years in those with >2/day (p = 0.005). After adjustment for age, pack-years of cigarette smoking, coffee consumption, laxative use, jogging, and the intake of fruits, vegetables, and grains, men with <1 bowel movement/day had a 2.7-fold excess risk of PD versus men with 1/day (95% CI: 1.3, 5.5; p = 0.007). The risk of PD in men with <1 bowel movement/day increased to a 4.1-fold excess when compared with men with 2/day (95% CI: 1.7, 9.6; p = 0.001) and to a 4.5-fold excess versus men with >2/day (95% CI: 1.2, 16.9; p = 0.025). CONCLUSIONS: Findings indicate that infrequent bowel movements are associated with an elevated risk of future PD. Further study is needed to determine whether constipation is part of early PD processes or is a marker of susceptibility or environmental factors that may cause PD.

Age Factors↗
PubMed2001

Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.

BACKGROUND: A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality. METHODS: Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71-93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models. FINDINGS: Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60 (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). INTERPRETATION: We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L) in elderly people.

Aged↗
PubMed2001

Accuracy of clinical criteria for AD in the Honolulu-Asia Aging Study, a population-based study.

OBJECTIVE: To determine diagnostic accuracy for AD in a population-based study of Japanese-American men. AD is neuropathologically confirmed for more than 80% of cases at major referral centers (primarily Caucasians); however, information on diagnostic accuracy in population-based studies and studies of different ethnic groups is limited. METHODS: There were 3,734 men who participated in the Honolulu-Asia Aging Study 1991 through 1993 dementia examination and 2,603 in the 1994 through 1996 examination. Diagnoses were based on published criteria. Neuropathologists blinded to clinical data quantified neurofibrillary tangles (NFT) and neuritic plaques (NP). RESULTS: Of 220 autopsied subjects, clinical evaluation revealed 68 with normal cognition, 73 intermediate, and 79 with dementia: 20 AD, 27 vascular dementia, 19 AD + other, and 13 other dementia. Among 20 cases with pure AD, the median value for maximum neocortical NFT density was 6.9/mm(2) and for neocortical NP density was 8.0/mm2. Corresponding densities for other groups were <3.0/mm2. Using established neuropathologic criteria, 25% (5/20) of clinical AD cases had enough NP to meet definite AD criteria, whereas 65% (13/20) had sufficient NP to meet neuropathologic definite or probable AD criteria. Among nine AD cases with moderately severe dementia, only two (22%) had NP densities great enough to meet definite neuropathologic criteria, whereas seven (78%) met neuropathologic criteria for probable AD. CONCLUSIONS: Neuropathologic confirmation and NP density among decedents with clinical AD in this population-based study were lower than reported by referral centers and similar to reports from two other community studies. Ethnic differences in propensity for amyloid deposition as well as differences in clinical severity and representativeness of cases might contribute to these findings.

Aged↗
PubMed2001

Ankle-brachial blood pressure in elderly men and the risk of stroke: the Honolulu Heart Program.

Although low ankle/brachial blood pressure index (ABI) is a marker of generalized atherosclerosis in the elderly, it has not been identified as a risk factor for stroke. The purpose of this report is to examine the relation between ABI and stroke in elderly men. ABI was measured from 1991 to 1993 in 2767 men aged 71 to 93 years in the Honolulu Heart Program without a history of stroke and coronary heart disease. Subjects were followed for 3 to 6 years for fatal and nonfatal thromboembolic and hemorrhagic stroke. During follow-up, there were 91 strokes. There was an age-adjusted 2-fold excess in men with an ABI < 0.9 (6.0%) versus men with an ABI > or = 0.9 (2.9%, P < 0.01). Thromboembolic events occurred in 4.6% of men with an ABI < 0.9 and in 2.0% in those with an ABI > or = 0.9 (P < 0.01). Hemorrhagic stroke was also more frequent in men with a low ABI (< 0.9) versus a higher ABI (1.9 vs. 0.8%, respectively). After adjusting for other factors, the risk of total and thromboembolic strokes increased with declining ABI (P = 0.019 and P = 0.004, respectively). The relation between ABI and stroke was similar and statistically significant in the presence and absence of diabetes and hypertension (P < 0.05). Findings suggest that ABI is inversely related to the incidence of stroke. Simple measurement of ABI in an outpatient setting could be an important tool for assessing the risk of stroke in the elderly.

Age Distribution↗
PubMed2001

The relationship of psychosocial factors to total mortality among older Japanese-American men: the Honolulu Heart Program.

OBJECTIVE: To examine the predictive value of psychosocial factors as risk factors for all-cause mortality. DESIGN: A community-based longitudinal cohort study: The Honolulu Heart Program. SETTING: Population-based study conducted in Oahu, Hawaii. PARTICIPANTS: Three thousand four hundred and ninety-seven men age 71 to 93 were examined and followed prospectively for all-cause mortality for an average of 6 years. MEASUREMENTS: Psychosocial data were obtained using the Lubben Social Networks Scale (LSNS). The LSNS consists of 10 items-family relationships (three items), relationships with friends (three items), and interdependent social supports and living arrangements (four items). We divided the LSNS score into quartiles for comparison, with the first quartile representing the lowest social support and the fourth quartile representing the highest social support. RESULTS: A significant dose-response relationship was noted with LSNS score and total mortality: 33.8% in the first quartile died over the follow-up period, 23.4% in the second, 18% in the third, and 15.7% in the fourth (P < .001). Six-year age-adjusted mortality rates were 66.2, 45.7, 37.8, and 33.7 per 1,000 person years in the first, second, third, and fourth, respectively (P < .001). Using age-adjusted Cox proportional hazards models, with the first quartile of LSNS as the reference group, relative risk for mortality was 0.69 (95% confidence interval (CI) = 0.58-0.82), 0.57 (95% CI = 0.47-0.70), and 0.52 (95% CI = 0.43-0.64) in the second, third, and fourth quartiles, respectively. Cox models were repeated, controlling for age and smoking status, and low LSNS scores remained significantly associated with higher mortality (P = .0001). CONCLUSIONS: Our findings suggest that social networks were significantly independently associated with 6-year all-cause mortality in this cohort of older Japanese-American men. Social interventions in old age may reduce early mortality.

Age Distribution↗
PubMed2001

Plasma fibrinogen as a predictor of total and cause-specific mortality in elderly Japanese-American men.

The relation between plasma fibrinogen and total and cause-specific mortality was investigated in a cohort of 3571 Japanese-American men aged 71 to 93 years during a median follow-up of 4.4 years. There were a total of 728 deaths, of which 37% were accounted for by cardiovascular disease and 27% by cancer. The age-adjusted relative risk (RR) for total mortality in the top quintile of fibrinogen (>3.51 g/L) compared with the bottom quintile (<2.57 g/L) was 4.3 (P<0.0001) in the first year of follow-up. RR was reduced to 1.7 in the second year but remained significantly and slightly increased in subsequent years. After adjustment for age and confounding risk factors, the RRs (and 95% confidence intervals) associated with a 1-SD increment of fibrinogen (0.64 g/L) for all-cause, cardiovascular disease, cancer, and other-cause mortality were 1.3 (1.2 to 1.4), 1.2 (1.1 to 1.4), 1.3 (1.2 to 1.5), and 1.3 (1.2 to 1.5), respectively. Preexisting diseases did not influence the significant association of fibrinogen with mortality. There was a significant interaction of fibrinogen with white blood cell count but not with cigarette smoking. We conclude that plasma fibrinogen is an independent risk factor for mortality from a broad spectrum of diseases in elderly men and that this universal effect of fibrinogen on mortality may be mediated partly through inflammation.

Aged↗
PubMed2001

beta(2)-Glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the honolulu heart program.

BACKGROUND: It has been hypothesized that immunoreactivity to beta(2)-glycoprotein 1 (beta2GP1)-dependent anticardiolipin antibody (aCL), but not beta2GP1-independent aCL, is associated with increased risk of ischemic stroke and myocardial infarction (MI). METHODS: We performed a nested case-control study examining aCL as a risk factor for ischemic stroke and MI by using stored frozen sera obtained from subjects enrolled in the Honolulu Heart Program and followed for up for 20 years. We measured beta2GP1-dependent and beta2GP1-independent aCL and anti-beta2GP1 immunoreactivity in 259 men who developed an ischemic stroke, in 374 men who developed an MI, and in a control group of 1360 men who remained free of both conditions. RESULTS: Only beta2GP1-dependent aCL of the IgG class was significantly associated with both incident ischemic stroke and MI. This association was attenuated in the last 5 years of the 20-year follow-up. For stroke, the risk factor-adjusted relative odds for men with a positive versus a negative beta2GP1-dependent aCL of the IgG class were 2.2 (95% CI 1.5 to 3.4) at 15 years and 1.5 (95% CI 1.0 to 2.3) at 20 years. For MI, the adjusted relative odds were 1.8 (95% CI 1.2 to 2.6) at 15 years and 1.5 (95% CI 1.1 to 2.1) at 20 years. CONCLUSIONS: These data suggest that aCL IgG, particularly the beta2GP1-dependent variety, is an important predictor of future stroke and MI in men.

Age Distribution↗