Association of olfactory dysfunction with risk for future Parkinson's disease.

OBJECTIVE: Although olfactory dysfunction is commonly associated with Parkinson's disease (PD), it is not known whether such dysfunction can predate the onset of clinical PD in a community-based population. This study examines the association of olfactory dysfunction with future development of PD in Honolulu-Asia Aging Study cohort members METHODS: Olfaction was assessed from 1991 to 1996 in 2,267 men in the Honolulu-Asia Aging Study aged 71 to 95 years who were free of clinical PD and dementia at the time of olfaction testing. Participants were followed for up to 8 years for incident PD RESULTS: In the course of follow-up, 35 men were diagnosed with PD (24.6/10,000 person-years). The average age at the time of diagnosis was 82.9 +/- 3.8 (range, 76-93) years, and the average time to a diagnosis was 4.0 +/- 1.9 (range, 1-8) years. During the first 4 years of follow-up, age-adjusted incidence of PD declined from 54.5/10,000 person-years in the lowest quartile of odor identification to 26.6, 8.2, and 8.4/10,000 person-years in the second, third, and fourth quartiles, respectively (p < 0.001 for trend). After adjustment for age and other potential confounders, the odds ratios for PD in the lowest quartile was 5.2 (95% confidence interval, 1.5-25.6) compared with the top two quartiles. This relation was not evident beyond 4 years of follow-up. INTERPRETATION: Impaired olfaction can predate clinical PD in men by at least 4 years and may be a useful screening tool to detect those at high risk for development of PD in later life.

Prospective association between low and high total and low-density lipoprotein cholesterol and coronary heart disease in elderly men.

OBJECTIVES: To examine the relationship between total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) in elderly men. DESIGN: Prospective. SETTING: Population based. PARTICIPANTS: A sample of 2,424, Japanese-American men aged 71 to 93 was used. MEASUREMENTS: Six years of data on incident fatal plus nonfatal CHD were examined. RESULTS: Analysis revealed a significant U-shaped relationship between age-adjusted CHD rates and both TC and LDL-C. The ranges of TC and LDL-C with the lowest risk of CHD were 200 to 219 mg/dL and 120 to 139 mg/dL, respectively. As cholesterol concentrations declined and increased beyond these ranges, the risk of CHD increased. These U-shaped relationships remained significant after adjusting for age and other risk factors. CONCLUSION: The U-shaped associations between TC and LDL-C and CHD imply a complex relationship between lipids and CHD in late life. The results indicate that elevated lipid levels should continue to be treated in healthy elderly individuals, as they are in those who are younger, although pharmacologically lowering lipids to excessively low levels in the elderly may warrant further study, as does the contribution of subclinical frailty to the relationship of lipids to CHD risk.

High density lipoprotein cholesterol and the risk of stroke in elderly men: the Honolulu heart program.

High density lipoprotein (HDL) cholesterol has been inversely associated with coronary heart disease. Associations with stroke are less clear, particularly among the elderly. In this study, the authors examined the relation between HDL cholesterol levels and the risk of stroke in elderly men. Levels of HDL cholesterol were measured in 2,444 Honolulu Heart Program men aged 71-93 years at the 1991-1993 examinations. The participants, who were free of prevalent stroke, coronary heart disease, and cancer at baseline, were followed to the end of 1998 for thromboembolic and hemorrhagic stroke. While HDL cholesterol was unrelated to hemorrhagic events, incidence of thromboembolic stroke declined consistently with increasing HDL cholesterol level (p = 0.003). There was a nearly threefold excess of thromboembolic stroke in men with low HDL cholesterol levels (<1.0 mmol/liter (<40 mg/dl)) compared with men with high levels (> or =1.6 mmol/liter (> or =60 mg/dl)) (10.6/1,000 person-years vs. 3.6/1,000 person-years; p = 0.001). Adjustment for other risk factors had little effect on these findings, although associations appeared strongest in elderly men with "desirable" total cholesterol levels, hypertension, or diabetes mellitus. These findings suggest that HDL cholesterol level is inversely related to the risk of thromboembolic stroke in elderly men. Whether HDL cholesterol alters the effect of other factors on stroke risk in elderly men warrants further study.

Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial.

BACKGROUND: Neurologic and clinical morbidity after coronary artery bypass grafting (CABG) can be significant. By avoiding cardiopulmonary bypass, off-pump CABG (OPCAB) may reduce morbidity. METHODS: Sixty patients (30 CABG and 30 OPCAB) were prospectively randomized. Neurocognitive testing was performed before the operation and 2 weeks and 1 year after the operation. Neurologic testing to detect stroke and (99m)Tc-HMPAO whole-brain single photon emission computed tomography scanning to assess cerebral perfusion were performed before the operation and 3 days afterward. Bilateral middle cerebral artery transcranial Doppler scanning was performed intraoperatively to detect cerebral microemboli. All examiners were blinded to treatment group. Clinical morbidity and costs were compared. RESULTS: Coronary artery bypass grafting was associated with more cerebral microemboli (575 +/- 278.5 CABG versus 16.0 +/- 19.5 OPCAB (median +/- semiinterquartile range) and significantly reduced cerebral perfusion after the operation to the bilateral occipital, cerebellar, precunei, thalami, and left temporal lobes (p < or = 0.01). Cerebral perfusion with OPCAB was unchanged. Compared with base line, OPCAB patients performed better on the Rey Auditory Verbal Learning Test (total and recognition scores) at both 2 weeks and at 1 year (p < or = 0.05), whereas CABG performance was statistically unchanged for all cognitive measures. Patients who underwent CABG had more chest tube drainage (1389 +/- 1256 mL CABG versus 789 +/- 586 mL OPCAB, p = 0.02) and required more blood (3.9 +/- 5.8 U CABG versus 1.2 +/- 2.2 U OPCAB, p = 0.02), fresh frozen plasma (3.0 +/- 6.0 U CABG versus 0.5 +/- 2.2 U OPCAB, p = 0.03), and hours of postoperative use of dopamine (16.3 +/- 21.2 hours CABG versus 7.3 +/- 9.7 hours OPCAB, p = 0.04). These differences culminated in higher costs for CABG ($23,053 +/- $5,320 CABG versus $17,780 +/- $4,390 OPCAB, p < 0.0001). One stroke occurred with CABG, compared with none with OPCAB (p = NS). One OPCAB patient died because of a pulmonary embolus (p = NS). CONCLUSIONS: Compared with CABG, OPCAB may reduce neurologic and clinical morbidity as well as cost.

Age-related changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke.

We examined the changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke as they may occur with age. Findings were based on repeated risk factor measurements at four examinations over a 26-year period in 7589 men in the Honolulu Heart Program. After each examination, 6 years of follow-up were available to assess risk factor effects on the incidence of stroke over a broad range of ages (45-93 years). As compared with normotensive men, the risk of thromboembolic stroke in the presence of hypertension declined from a 7-fold excess in men aged 45 to 54 years to a 1.4-fold excess in men aged > or =75 (P<.001). Adverse effects of diabetes and atrial fibrillation seemed to be equally important across all ages, whereas a protective effect of physical activity increased with age. Except for men with atrial fibrillation, the incidence of thromboembolic stroke increased significantly with age regardless of risk factor status, including men with normal blood pressure (P<.001). Although hemorrhagic events were less common, positive relations with cigarette smoking seemed to strengthen with age, whereas those with hypertension tended to decline. Our findings suggest that strategies for the prevention of stroke may need to account for changes in risk factor effects as they occur with age. Control of diabetes and the encouragement of active lifestyles in the elderly seem to be especially important.

C-reactive protein and the future risk of thromboembolic stroke in healthy men.

BACKGROUND: Evidence suggests that C-reactive protein (CRP) is related to thromboembolic (TE) stroke. Whether associations are altered in the presence of other risk factors is unclear. The purpose of this study was to additionally assess the relation between CRP and TE stroke. METHODS AND RESULTS: On the basis of 20 years of follow-up after CRP measurement, 259 cases of TE stroke were identified and compared with 1348 controls. Subjects were aged 48 to 70 years when CRP was measured. Levels of CRP were positively associated with TE stroke throughout the 20 years of follow-up. Although associations were modest within 5 years of CRP measurement, the odds of stroke in the top versus bottom CRP quartile increased over time to a 3.8-fold excess by 10 to 15 years into follow-up (P<0.001). For men without hypertension or diabetes, the overall corresponding odds were 1.6 to 1.7 (P<0.05). In men 55 years of age, and in those with hypertension or diabetes were not significant. CONCLUSIONS: Findings suggest that elevated CRP in middle adulthood and in men with healthier risk factor profiles may be important as a risk factor for TE stroke. Use of CRP levels as a clinical screen to identify an increased risk of cardiovascular disease in otherwise healthy men warrants consideration.

Plantation work and risk of Parkinson disease in a population-based longitudinal study.

CONTEXT: Parkinson disease (PD) has an unknown cause; however, convincing evidence is emerging that indicates pesticides can selectively injure the dopaminergic system in laboratory animals. Retrospective studies in humans demonstrate a link between exposure to agricultural lifestyle factors and PD. OBJECTIVE: To determine whether working on a plantation in Hawaii and exposure to pesticides are associated with an increased risk of PD decades later. DESIGN AND SETTING: Prospective cohort study based on the island of Oahu, Hawaii, with 30 years of follow-up. Years of work on a plantation were assessed by questionnaire at study enrollment in 1965. Self-reported information on pesticide exposure was collected at a separate examination 6 years later. PARTICIPANTS: Participants were 7986 Japanese American men born between 1900 and 1919 who were enrolled in the longitudinal Honolulu Heart Program. MAIN OUTCOME MEASURES: Incident PD was determined by medical record review or by an examination conducted by a study neurologist at a later date. RESULTS: During follow-up, 116 men developed PD. Age-adjusted incidence increased significantly among men who worked more than 10 years on a plantation. The relative risk of PD was 1.0 (95% confidence interval, 0.6-1.6), 1.7 (95% confidence interval, 0.8-3.7), and 1.9 (95% confidence interval, 1.0-3.5) for men who worked on a plantation 1 to 10 years, 11 to 20 years, and more than 20 years compared with men who never did plantation work (P =.006, test for trend). Age-adjusted incidence of PD was higher in men exposed to pesticides than in men not exposed to pesticides although this was not statistically significant (P =.10, test for trend). CONCLUSION: These longitudinal observations regarding plantation work in Hawaii support case-control studies suggesting that exposure to pesticides increases the risk of PD.

Risk of hospitalized stroke in men enrolled in the Honolulu Heart Program and the Framingham Study: A comparison of incidence and risk factor effects.

BACKGROUND AND PURPOSE: Risk of death due to stroke in Japan is more than double the risk in the United States. It remains unknown why some ethnic groups are more prone to stroke than others. Our purpose was to compare the 20-year incidence of hospitalized stroke between Japanese-American men in the Honolulu Heart Program and white men in the Framingham Study. METHODS: This was a 20-year follow-up study beginning around 1965, a population-based study on the island of Oahu, Hawaii, and in Framingham, Mass. Participants were 7589 men in Honolulu and 1216 men in Framingham without prevalent coronary heart disease and stroke. Subjects were 45 to 68 years old when follow-up began. Main outcome measures were incident thromboembolic and hemorrhagic stroke. RESULTS: Framingham men had a 40% excess of thromboembolic stroke compared with Honolulu men after adjustment for age and other risk factors (62/1000 versus 45/1000, respectively, P<0.001), whereas incidence of hemorrhagic stroke was nearly identical (14.8/1000). In both cohorts, each stroke type was consistently elevated in the presence of hypertension and cigarette smoking. Diabetes and body mass index increased the risk of thromboembolic stroke in both samples, and diabetes increased the risk of hemorrhagic events in Framingham. Alcohol intake and low total cholesterol were associated with hemorrhagic events in Honolulu but not in Framingham. Despite occasional differences in risk factor effects, none were significantly different between cohorts. CONCLUSIONS: The incidence of thromboembolic stroke requiring hospitalization is markedly less in Honolulu than in Framingham. The difference in stroke incidence rates observed cannot be explained by the traditional risk factors. Further studies are needed to identify factors that protect Japanese-American men in Honolulu from stroke.