Elderly Japanese-American Men Research Articles

Session 411 - Research in Dementia and Depression in Elderly Japanese-American Men: The Kuakini Honolulu-Asia Aging Study

Session 411 - Research in Dementia and Depression in Elderly Japanese-American Men: The Kuakini Honolulu-Asia Aging Study

Total and differential white blood cell counts in late life predict 8-year incident stroke: the Honolulu Heart Program.

To study the association between total and differential white blood cell (WBC) count and incident stroke in an older Asian population. Prospective population-based study with 8 years of follow-up. The Honolulu Heart Program, Oahu, Hawaii. Japanese-American men aged 71 to 93 who were free of stroke and had baseline WBC counts measured in 1991-93 (N=3,342). Participants were divided into quartiles of total and differential WBC count for analysis and were followed for incident stroke (thromboembolic and hemorrhagic (hemorrhagic)) for 8 years using data from a comprehensive hospital surveillance system. Age-adjusted incident stroke rates increased significantly with increasing WBC quartile (Q1, 7.68; Q2, 9.04; Q3, 9.26; Q4, 14.10 per 1,000 person-years of follow-up, P=.001). Hazard ratios (HRs) for stroke for each quartile of total and differential WBC count were obtained using Cox regression analysis, with the lowest quartile as the reference group. After full adjustment, including age; cardiovascular risk factors; fibrinogen; prevalent coronary heart disease, cancer, or chronic obstructive pulmonary disease, and nonsteroidal anti-inflammatory drug use, HRs were 1.62 (95% confidence interval (CI)=1.04-2.52, P=.03) in the highest quartile of total WBC and 2.19 (95% CI=1.41-3.39, P<.001) in the highest quartile of neutrophil counts. Significant associations were also seen for thromboembolic but not for hemorrhagic strokes. No significant associations were found between lymphocyte or monocyte counts and incident stroke or subtypes. In elderly Japanese-American men, higher total WBC and neutrophil counts were independent predictors of overall stroke, as well as thromboembolic stroke.

Total and differential white blood cell counts predict eight-year incident coronary heart disease in elderly Japanese-American men: The Honolulu Heart Program

Background: Previous studies have reported an association between total and differential white blood cell (WBC) counts and incident coronary heart disease (CHD), but data from elderly populations are scarce. The purpose of this study was to examine the association between total and differential WBC counts and incident CHD in an elderly Japanese-American population. Methods: Total and differential WBC counts were examined at a baseline examination from 1991 to 1993 in the Honolulu Heart Program. Subjects were Japanese-American men aged 71–93 years free of CHD at baseline (N = 2879), who were divided into quartiles of total and differential WBC counts for analysis, and were followed for incident CHD for 8 years. Results: During the follow up period, 279 men developed CHD. Hazard ratio for incident CHD for each quartile of total and differential WBC counts were obtained by Cox regression using the lowest quartile as the reference group. After full adjustment including age, cardiovascular risk factors, chronic diseases and medication use, the hazard ratios in the highest quartiles of total WBC, granulocyte and neutrophil counts were 1.75 (95% confidence interval [CI], 1.18–2.62; P = 0.006), 1.66 (95%CI, 1.11–2.48; P = 0.01), and 1.57 (95%CI, 1.06–2.34; P = 0.03), respectively. No significant associations were found between lymphocyte or monocyte counts and incident CHD. Conclusions: Higher total WBC, granulocyte and neutrophil counts were associated with higher risk of incident CHD in a population of elderly Japanese-American men. Further studies are needed to establish cut-points and treatment options with anti-inflammatory medications.

Antihypertensive medication use and risk of cognitive impairment

To determine the associations between classes of antihypertensive medication use and the risk of cognitive impairment among elderly hypertensive men. The Honolulu-Asia Aging Study is a prospective, community-based cohort study of Japanese American men conducted in Honolulu, Hawaii. We examined 2,197 participants (mean age 77 years at cohort entry, 1991-1993, followed through September 2010) with hypertension and without dementia or cognitive impairment at baseline, who provided information on medication use. Cognitive function was assessed at 7 standardized examinations using the Cognitive Abilities Screening Instrument (CASI). Cognitive impairment was defined as a CASI score <74. A total of 854 men developed cognitive impairment (median follow-up, 5.8 years). β-Blocker use as the sole antihypertensive drug at baseline was consistently associated with a lower risk of cognitive impairment (incidence rate ratio [IRR] 0.69; 95% confidence interval [CI] 0.50-0.94), as compared with men not taking any antihypertensive medications, adjusting for multiple potential confounders. The use of diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or vasodilators alone was not significantly associated with cognitive impairment. Results were similar excluding those with cardiovascular disease or <1 year of follow-up, and additionally adjusting for pulse pressure, heart rate, baseline and midlife systolic blood pressure, and midlife antihypertensive treatment (IRR 0.65; 95% CI 0.45-0.94). The association between β-blocker use and cognitive impairment was stronger among men with diabetes, men aged >75 years, and those with pulse pressure ≥70 mm Hg. β-blocker use is associated with a lower risk of developing cognitive impairment in elderly Japanese American men.

Does Cultural Assimilation Influence Prevalence and Presentation of Depressive Symptoms in Older Japanese American Men? The Honolulu-Asia Aging Study

: Sociocultural factors have been implicated in affecting prevalence, incidence, and diagnosis of depression but previous studies have included heterogeneous ethnic populations. We studied the influence of cultural assimilation on the prevalence and presentation of depressive symptoms in elderly Japanese American men. : This analysis was based on 3,139 Japanese American men aged 71-93 years who were participants in the Honolulu-Asia Aging Study between 1991 and 1993. We created a Cultural Assimilation Scale (CAS) using 8 questions assessing the degree of Japanese identity and lifestyle compared to a Western one. Subjects were divided into tertiles of CAS score for analysis. Prevalence of depressive symptoms was measured using an 11-question version of the Centers for Epidemiologic Studies Depression Scale questionnaire, and presence of depressive symptoms was defined as score 9 or more. : Prevalent depressive symptoms did not reach a statistically significant association with CAS tertiles (Western, 10.8%; Mixed, 9.6%; and Japanese, 8.5%). However after adjusting for demographic, functional, and disease factors, the most culturally Japanese group had significantly lower odds for prevalent depressive symptoms, compared to the most Western group. Among the subset of subjects with a high-Centers for Epidemiologic Studies Depression Scale-11 score, there were no significant differences in both mean psychological scores and mean somatic scores between the three CAS groups. : Prevalent depressive symptoms were significantly lower among elderly Japanese American men who were most culturally Japanese, compared to more westernized men. Improving knowledge and understanding about the pathogenesis of depression will have important public health implications.

White Matter Lesions on Brain Magnetic Resonance Imaging Scan and 5‐Year Cognitive Decline: The Honolulu‐Asia Aging Study

To study white matter lesions (WMLs) and 5-year cognitive decline in elderly Japanese-American men. Longitudinal cohort study. Population-based study in Honolulu, Hawaii. Japanese-American men aged 74 to 95 from the Honolulu-Asia Aging Study (HAAS) who were free of prevalent dementia, underwent a protocol brain MRI scan at the fifth HAAS examination (1994-1996), and returned for cognitive testing 5 years later (N=267). WMLs were dichotomized as present (grade 3-9, 38.2%) or absent (grade 1-2, 61.8%). Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI), and 5-year cognitive decline was defined as a drop in CASI score of 12 points or more (1 standard deviation). Men with WMLs on MRI at baseline were significantly more likely to experience cognitive decline at 5 years than those without (22.4% vs 34.4%, P=.03). Using multiple logistic regression, adjusting for age, education, apolipoprotein (Apo)E4 allele, large or small infarcts on MRI, baseline CASI score, and hypertension, those with WMLs were significantly more likely to develop 5-year cognitive decline (odds ratio=2.00, 95% confidence interval=1.10-3.65, P=.02). This association was stronger in men who were cognitively intact and free of the ApoE4 genotype and clinical stroke at baseline. Presence of WMLs on MRI was significantly associated with higher odds of 5-year cognitive decline in older Japanese-American men. Presence of WMLs may help identify people at risk for developing dementia, who may benefit from early intervention.

Effect of Walking Distance on 8‐Year Incident Depressive Symptoms in Elderly Men with and without Chronic Disease: The Honolulu‐Asia Aging Study

To determine the effect of walking on incident depressive symptoms in elderly Japanese-American men with and without chronic disease. Prospective cohort study. The Honolulu-Asia Aging Study. Japanese-American men aged 71 to 93 at baseline. Physical activity was assessed according to self-reported distance walked per day. Depressive symptoms were measured using an 11-question version of the Centers for Epidemiologic Studies Depression Scale (CES-D 11) at the fourth examination (n=3,196) and at the seventh examination 8 years later (1999/00, n=1,417). Presence of incident depressive symptoms was defined as a CES-D 11 score of 9 or greater or taking antidepressants at Examination 7. Subjects with prevalent depressive symptoms at baseline were excluded. Age-adjusted 8-year incident depressive symptoms were 13.6%, 7.6%, and 8.5% for low (<0.25 miles/day), intermediate (0.25-1.5 miles/day), and high (>1.5 miles/day) walking groups at baseline (P=0.008). Multiple logistic regression analyses, adjusted for age, education, marital status, cardiovascular risk factors, prevalent diseases, and functional impairment, showed that those in the intermediate and highest walking groups had significantly lower odds of developing 8-year incident depressive symptoms (odds ratio (OR)=0.52, 95% confidence interval (CI)=0.32-0.83, P=.006 and OR=0.61, 95% CI= 0.39-0.97, P=.04, respectively). Analysis found that this association was significant only in participants without chronic diseases (coronary heart disease, cerebrovascular accident, cancer, Parkinson's disease, dementia, or cognitive impairment) at baseline. Daily physical activity (≥0.25 mile/day) is significantly associated with lower risk of 8-year incident depressive symptoms in elderly Japanese-American men without chronic disease at baseline.

Association of Fibrinogen with Parkinson Disease in Elderly Japanese-American Men: A Prospective Study

Background: The purpose of this prospective study was to examine whether fibrinogen level is associated with Parkinson disease (PD) for both prevalent and incident cases. Methods: The Honolulu Asia-Aging Study is a longitudinal study of Japanese-American men based on the Honolulu Heart Study birth cohort. The original cohort consisted of 8,006 participants with selective service records who were living on the island of Oahu, Hawaii, in 1965. For this analysis, baseline was defined as the 1991–1993 examination (n = 3,845) when men were aged 71–93 years old. Multivariate logistic regression and Cox proportional hazards models were used, adjusting for potential confounders. Results: We identified 61 prevalent cases and 61 incident cases of PD during the follow-up. High fibrinogen level (presence in the top quintile) was associated with higher frequency of PD for both prevalent (OR = 2.07, 95% CI = 1.10–3.88, p = 0.024) and incident cases (HR = 3.05, 95% CI = 1.34–6.97, p = 0.008) among men aged 76–93 years, after adjusting for age, smoking, and low-density lipoprotein cholesterol. Conclusions: These results suggest high fibrinogen level is associated with increased risk of PD among men over 75 years.

World War II Vets Study Still Providing MH Data

World War II Vets Study Still Providing MH Data

Factors Associated with Place of Death for Elderly Japanese‐American Men: The Honolulu Heart Program and Honolulu‐Asia Aging Study

Place of death is an indicator of health service utilization at the end of life and differs according to cause of death. Asian Americans may have a higher percentage of hospital deaths than Caucasian Americans, yet reasons for this finding are unclear. This study examined distribution of place of death and the associations between place and cause of death in elderly Japanese-American men in a longitudinal cohort: the Honolulu Heart Program and Honolulu-Asia Aging Study. Data collected between 1991 and 1999 on 1,352 men aged 73 to 99 at death were analyzed for associations between cause-of-death characteristics and hospital, home, or nursing home location of death. Fifty-nine percent of men died in hospitals, 23% died at home, and 18% died in nursing homes. Of the dementia-related deaths, 43% occurred in hospitals (vs 16% in a national study), 37% occurred in nursing homes (vs 67% in a national study), and 20% occurred at home. Of the stroke deaths, 53% occurred in hospitals, 40% were in nursing homes, and 7% occurred at home. Of the cancer deaths, 53% occurred in hospitals, 34% occurred at home, and 13% were in nursing homes. Traditional family obligation to care for elderly people at home and inability to access care for dementia may account for the greater rate of hospital death and lower rate of nursing home deaths in this cohort. Attitudes of elderly Japanese Americans and their families regarding place of care at the end of life, particularly in the setting of dementia, merit future study.

Resting Heart Rate and All-Cause Mortality in Elderly Japanese-American Men: The Honolulu Heart Program

Introduction/Objective: Elevated heart rate is a significant predictor for cardiovascular death in many studies. We studied whether resting heart rate in mid-life and in late-life is a risk for mortality in Japanese-American men, a population that has not been previously studied.

A Prospective Study of High-Density Lipoprotein Cholesterol, Cholesteryl Ester Transfer Protein Gene Variants, and Healthy Aging in Very Old Japanese-American Men

High-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) gene deficiency mutations that increase HDL-C levels have been associated with exceptional longevity. However, a recent clinical trial of a promising CETP inhibitor that markedly increases HDL-C was terminated due to increased mortality. In light of this controversy, we examined the relationship among HDL-C, CETP mutations, and longevity phenotypes in the long-lived Japanese-American men of the Honolulu Heart Program (HHP). Japanese-American men (n = 3562) were followed for up to 8 years, from average age 78 to average age 84 (maximum age 99), or until death. Total mortality, cause-specific mortality, and healthy survival were evaluated for associations with HDL-C level and CETP genetic variants common in the Japanese population (CD442G and Int 14A). HDL-C was negatively associated with cardiovascular disease (CVD) mortality (p =.002) but not related to non-CVD (p =.147) or total (p =.547) mortality after adjustment for common risk factors. There was a trend for lower mortality for the men with the Int 14A variant. These men also had higher HDL-C levels (p =.047) and were significantly more likely to be healthy survivors (absence of six major age-related diseases and high physical/cognitive function) beyond the age of 90 years (p =.005). Low HDL-C level is a risk factor for CVD mortality in elderly Japanese-American men. High HDL-C and the Int 14A variant of the CETP gene may increase odds for healthy aging.

Association of olfactory dysfunction with incidental Lewy bodies

Olfactory dysfunction is found in early Parkinson's disease (PD) and in asymptomatic relatives of PD patients. Incidental Lewy bodies (ILB), the presence of Lewy bodies in the brains of deceased individuals without a history of PD or dementia during life, are thought to represent a presymptomatic stage of PD. If olfactory dysfunction were associated with the presence of ILB, this would suggest that olfactory deficits may precede clinical PD. The purpose of this study was to determine the association of olfactory dysfunction during late life with ILB in the substantia nigra or locus ceruleus. Olfaction was assessed during the 1991-1994 and 1994-1996 examinations of elderly Japanese-American men participating in the longitudinal Honolulu-Asia Aging Study. Among those who later died and underwent a standardized postmortem examination, brains were examined for Lewy bodies in the substantia nigra and the locus ceruleus with hematoxylin and eosin stain. Lewy bodies in the brains of individuals without clinical PD or dementia were classified as ILB. There were 164 autopsied men without clinical PD or dementia who had olfaction testing during one of the examinations. Seventeen had ILB. The age-adjusted percent of brains with ILB increased from 1.8% in the highest tertile of odor identification to 11.9% in the mid-tertile to 17.4% in the lowest tertile (P = 0.019 in test for trend). Age-adjusted relative odds of ILB for the lowest versus the highest tertile was 11.0 (P = 0.02). Olfactory dysfunction is associated with ILB. If incidental Lewy bodies represent presymptomatic stage of PD, olfactory testing may be a useful screening tool to identify those at high risk for developing PD.

Analysis and validation of automated skull stripping tools: A validation study based on 296 MR images from the Honolulu Asia aging study

As population-based epidemiologic studies may acquire images from thousands of subjects, automated image post-processing is needed. However, error in these methods may be biased and related to subject characteristics relevant to the research question. Here, we compare two automated methods of brain extraction against manually segmented images and evaluate whether method accuracy is associated with subject demographic and health characteristics. MRI data ( n = 296) are from the Honolulu Asia Aging Study, a population-based study of elderly Japanese–American men. The intracranial space was manually outlined on the axial proton density sequence by a single operator. The brain was extracted automatically using BET (Brain Extraction Tool) and BSE (Brain Surface Extractor) on axial proton density images. Total intracranial volume was calculated for the manually segmented images (ticvM), the BET segmented images (ticvBET) and the BSE segmented images (ticvBSE). Mean ticvBSE was closer to that of ticvM, but ticvBET was more highly correlated with ticvM than ticvBSE. BSE had significant over (positive error) and underestimated (negative error) ticv, but net error was relatively low. BET had large positive and very low negative error. Method accuracy, measured in percent positive and negative error, varied slightly with age, head circumference, presence of the apolipoprotein eε4 polymorphism, subcortical and cortical infracts and enlarged ventricles. This epidemiologic approach to the assessment of potential bias in image post-processing tasks shows both skull-stripping programs performed well in this large image dataset when compared to manually segmented images. Although method accuracy was statistically associated with some subject characteristics, the extent of the misclassification (in terms of percent of brain volume) was small.

The Prevalence and Prognosis of a Brugada-type Electrocardiogram in a Population of Middle-aged Japanese-American Men with Follow-up of Three Decades

The Brugada syndrome is an inherited arrhythmogenic and nonstructural heart disease associated with an increased risk of sudden cardiac death from ventricular fibrillation. There are conflicting data about its prevalence and prognosis. Particularly, population-based studies are lacking in the United States and other countries. A total of 8006 Japanese-American men aged 45 to 68 years participated in the initial examination of the Honolulu Heart Program during the period of 1965 through 1968. After excluding prevalent cases with coronary heart disease, 864 electrocardiograms coded as right bundle branch block were reviewed using the specified criteria for Brugada-type electrocardiogram. Baseline characteristics and the prognosis of Brugada-type electrocardiogram were compared with 5983 control subjects who had electrocardiograms coded as normal at the initial examination. There were 12 typical cases and 11 atypical cases of Brugada-type electrocardiogram at the initial examination (prevalence, 0.15% and 0.14%, respectively). Analysis of baseline characteristics revealed no difference between control cases and either typical or atypical Brugada-type electrocardiogram cases except significantly lower body mass index in subjects with Brugada-type electrocardiogram. During the 30-year follow-up period, none of the subjects died suddenly within 24 hours after the onset of symptoms. Survival analysis revealed no significant difference between case and control groups. Brugada-type electrocardiograms among middle-aged or elderly Japanese-American men are uncommon and are not associated with increased risk of either sudden death or total mortality.

The relationship of depressive symptoms and cardiovascular disease in elderly Japanese–American men

Penile curvature is one of the most common male conditions, affecting nearly 10% of men, and can impair sexual intercourse. Tunica albuginea (hTA) plays a key role in penile curvature, and reconstructive procedures may be necessary for its substitution. Although several grafts have been proposed for hTA repair, the ideal graft is not yet available.The aim of this article is to evaluate a new human tunica albuginea acellular matrix (hTAAM) as potential graft for penile reconstructive procedures.Twelve penises were obtained during sex reassignment surgeries from male‐to‐female transsexual patients. After dissection, hTAs were assigned into two groups according to the decellularization methods: polyethylene glycol (PEG) 1000 method following ultraviolet‐C radiation, and Triton X‐100 modified method.Structural analyses were assessed by hematoxilin and eosin, Masson's trichrome, Weigert's, and picrosirius‐polarization staining methods. Total protein, total glycosaminoglycan (GAG), and nucleic acid (DNA and RNA) concentrations were assessed by specific biochemical analyses. Uniaxial strength tests were performed to evaluate biomechanical properties.All hTAAMs presented no nuclear or cellular remnants. Total protein concentration was significantly higher in PEG 1000 hTAAM. Despite GAG concentration decreased significantly in hTAAM, Triton X‐100 hTAAM retained the highest GAG concentration (1.0 ± 0.42 µg HexUr/mg dry tissue, P > 0.05). All decellularization methods were efficacious to remove nucleic acids. The maximal break point presented no difference between hTA and hTAAM groups (P > 0.05).PEG 1000 and Triton X‐100 decellularization methods provide equally successful hTAAMs, preserving original structural and biochemical properties. da Silva FG, Filho AM, Damião R, and da Silva EA. Human acellular matrix graft of tunica albuginea for penile reconstruction. J Sex Med 2011;8:3196–3203.

Sleep-disordered breathing and cognitive impairment in elderly Japanese-American men.

To assess the association between sleep-disordered breathing and cognitive functioning in an elderly cohort of Japanese-American men. Cross-sectional study. The Honolulu-Asia Aging Study of Sleep Apnea, Oahu, Hawaii. 718 men between 79 and 97 years of age examined in 1999 and 2000. Apnea-hypopnea index from in-home overnight polysomnography, performance on the Cognitive Abilities Screening Instrument, body mass index, neck circumference, Epworth Sleepiness Scale, snoring, Center for Epidemiologic Studies Depression 11-item depression scale, physical disability, and history of heart disease, stroke, hypertension, diabetes, and dementia. Less than 30% of the men had no sleep-disordered breathing (apnea-hypopnea index < 5) and nearly one-fifth (19%) had severe sleep-disordered breathing (apnea-hypopnea index > or = 30). Severe sleep-disordered breathing was associated with higher body mass index, habitual snoring, and daytime drowsiness. No association was found between sleep-disordered breathing and cognitive functioning, including measures of memory function, concentration, and attention. Sleep-disordered breathing was associated with more drowsiness but not with poor performance on standardized cognitive tests used to screen for Alzheimer disease and other dementias in older persons. Because a healthy-participant effect may have contributed to this finding, more extensive cognitive testing may be necessary to reveal more subtle deficits from sleep-disordered breathing.

Are depressive symptoms a risk factor for mortality in elderly Japanese American men?: the Honolulu-Asia Aging Study.

This study determined the influence of depressive symptoms on subsequent mortality of all causes. The Honolulu Heart Program, established in 1965, is a prospective, community-based cohort of Japanese American men living in Hawaii. The analysis was based on 3,196 Japanese American men aged 71-93 at the time of the fourth examination in 1991-1993. Depressive symptoms were measured by use of an 11-question version of the Centers for Epidemiologic Studies Depression Scale questionnaire. All-cause mortality data were available for 6 years of follow up. Data were analyzed on the basis of presence or absence of chronic diseases. The overall prevalence of frequent depressive symptoms was 9.9%. Age-adjusted mortality rates at 3 years were 48.0 and 30.3 per 1,000 person-years for the depressed and nondepressed groups, respectively. At 6 years, the rates were 54.1 (depressed) and 41.5 (nondepressed) per 1,000 person-years. After adjustment for age, marital status, and antidepressant use, the relative risk for all-cause mortality associated with depressive symptoms was 1.53 for 3-year and 1.27 for 6-year mortality. Among participants who were healthy (without cognitive impairment, coronary heart disease, stroke, diabetes, or cancer), the association between depressive symptoms and mortality was greater (relative risk of 2.30 and 1.57 for 3- and 6-year mortality, respectively). Among participants with chronic disease, there were no significant associations between depressive symptoms and mortality. Depressive symptoms are a risk factor for mortality in elderly people, particularly in physically healthy individuals.

The American Diabetes Association and World Health Organization classifications for diabetes: their impact on diabetes prevalence and total and cardiovascular disease mortality in elderly Japanese-American men.

To compare the prevalence of diabetes according to the American Diabetes Association (ADA) and World Health Organization (WHO) classifications in a sample of elderly Japanese-American men; to examine the association with total and cardiovascular mortality by diabetes status using both classifications; and to determine whether the fasting or 2-h glucose measurement is a stronger predictor of adverse outcomes. Examinations given from 1991 to 1993 in the Honolulu Heart Program were used as baseline for these analyses. Subjects were 71-93 years of age at that time and were followed for total and cardiovascular disease mortality for up to 7 years. A total of approximately 66% of individuals who had diabetes by WHO criteria were missed when the ADA definition was used. The relative risks of total and cardiovascular mortality for those with versus those without diabetes were similar for both definitions; however, when fasting and postload glucose measures were analyzed as continuous variables, the 2-h measurement was a superior predictor and was independent of fasting glucose. In contrast, fasting glucose was not an independent predictor of these outcomes in the presence of the 2-h measurement. The prevalence of glucose metabolism abnormalities was very high among elderly Japanese-American men. The WHO classification was superior to the ADA classification in identification of subjects at high risk for adverse outcomes. Therefore, we conclude that the 2-h glucose measurement is valuable and should be retained in epidemiologic studies.

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.