Search

Context: Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction., Objective: To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction., Data Sources: Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies., Study Selection: Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality., Data Extraction: Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease., Results: Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women., Conclusion: Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

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.

Context: The projected expansion in the next several decades of the elderly population at highest risk for Parkinson disease (PD) makes identification of factors that promote or prevent the disease an important goal., Objective: To explore the association of coffee and dietary caffeine intake with risk of PD., Design, Setting, and Participants: Data were analyzed from 30 years of follow-up of 8004 Japanese-American men (aged 45-68 years) enrolled in the prospective longitudinal Honolulu Heart Program between 1965 and 1968., Main Outcome Measure: Incident PD, by amount of coffee intake (measured at study enrollment and 6-year follow-up) and by total dietary caffeine intake (measured at enrollment)., Results: During follow-up, 102 men were identified as having PD. Age-adjusted incidence of PD declined consistently with increased amounts of coffee intake, from 10.4 per 10,000 person-years in men who drank no coffee to 1.9 per 10,000 person-years in men who drank at least 28 oz/d (P<.001 for trend). Similar relationships were observed with total caffeine intake (P<.001 for trend) and caffeine from non-coffee sources (P=.03 for trend). Consumption of increasing amounts of coffee was also associated with lower risk of PD in men who were never, past, and current smokers at baseline (P=.049, P=.22, and P=.02, respectively, for trend). Other nutrients in coffee, including niacin, were unrelated to PD incidence. The relationship between caffeine and PD was unaltered by intake of milk and sugar., Conclusions: Our findings indicate that higher coffee and caffeine intake is associated with a significantly lower incidence of PD. This effect appears to be independent of smoking. The data suggest that the mechanism is related to caffeine intake and not to other nutrients contained in coffee. JAMA. 2000;283:2674-2679.

Context: Poor muscle strength, functional limitations, and disability often coexist, but whether muscle strength during midlife predicts old age functional ability is not known., Objective: To determine whether hand grip strength measured during midlife predicts old age functional limitations and disability in initially healthy men., Design and Setting: A 25-year prospective cohort study, the Honolulu Heart Program, which began in 1965 among Japanese-American men living on Oahu, Hawaii., Participants: A total of 608945- to 68-year-old men who were healthy at baseline and whose maximal hand grip strength was measured from 1965 through 1970. Altogether, 2259 men died over the follow-up period and 3218 survivors participated in the disability assessment in 1991 through 1993., Main Outcome Measures: Functional limitations including slow customary walking speed (< or =0.4 m/s) and inability to rise from a seated position without using the arms, and multiple self-reported upper extremity, mobility, and self-care disability outcomes., Results: After adjustment for multiple potential confounders, risk of functional limitations and disability 25 years later increased as baseline hand grip strength, divided into tertiles, declined. The odds ratio (OR) of walking speed of 0.4 m/s or slower was 2.87 (95% confidence interval [CI], 1.76-4.67) in those in the lowest third and 1.79 (95% CI, 1.14-2.81) in the middle third of grip strength vs those in the highest third. The risk of self-care disability was more than 2 times greater in the lowest vs the highest grip strength tertile. Adding chronic conditions identified at follow-up to the models predicting disability reduced the ORs related to grip strength only minimally., Conclusions: Among healthy 45- to 68-year-old men, hand grip strength was highly predictive of functional limitations and disability 25 years later. Good muscle strength in midlife may protect people from old age disability by providing a greater safety margin above the threshold of disability.

Context: Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known., Objective: To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension., Design: Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial., Participants: A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP)., Intervention: Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo., Main Outcome Measures: Fatal and nonfatal heart failure., Results: During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure., Conclusion: In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed.

Objective: To determine the frequency of unrecognized dementia in a group of men found to have dementia by population survey, and to identify factors associated with the failure of a family informant to recognize significant memory impairment., Design and Setting: The Honolulu-Asia Aging Study, a population-based study of dementia among elderly Japanese-American men living on the island of Oahu, Hawaii. Data for this study were from the dementia prevalence survey, 1991-1993., Study Participants: A total of 191 noninstitutionalized men with dementia who had a reliable family informant., Main Outcome Measures: Failure of family informants to recognize a problem with thinking or memory in subjects with dementia., Results: A total of 21% of family informants failed to recognize a problem with memory among subjects subsequently found to have dementia. Among subjects with very mild dementia, 52% of family informants failed to recognize a significant memory problem compared with 13% among more severely demented subjects. Of the subjects with dementia whose family informants did recognize a memory problem, 53% failed to receive a medical evaluation for this problem. For all family informants, increasing age, fewer years of education, less severe dementia, fewer behavioral complications, fewer functional disabilities, and better performance on certain tests of memory and language were significantly associated with the family informant's failure to recognize a problem with memory. When the family informants were wives living with husbands, less severe dementia, fewer behavioral complications, fewer functional disabilities, and intact remote memory were associated with unrecognized dementia., Conclusions: Unrecognized dementia was common in our population, especially among mild cases. Cognitive screening programs for the elderly and public education policies designed to increase awareness of early signs of dementia are needed if interventions for individuals with potentially treatable dementias are to be implemented.

Objective: To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients., Design: Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP)., Setting: Multiple clinical and support centers in the United States., Participants: A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (> or = 140 mg/dL), or any combination of these characteristics., Intervention: The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patient's private physician for persistently high BP., Main Outcome Measures: The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality., Results: The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients., Conclusion: Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.

Objective: To determine prevalence of dementia and its subtypes in Japanese-American men and compare these findings with rates reported for populations in Japan and elsewhere., Design and Setting: The Honolulu Heart Program is a prospective population-based study of cardiovascular disease established in 1965. Prevalence estimates were computed from cases identified at the 1991 to 1993 examination. Cognitive performance was assessed using standardized methods, instruments, and diagnostic criteria., Participants: Subjects were 3734 Japanese-American men (80% of surviving cohort) aged 71 through 93 years, living in the community or in institutions., Main Outcome Measures: Age-specific, age-standardized, and cohort prevalence estimates were computed for dementia (all cause) defined by 2 sets of diagnostic criteria and 4 levels of severity. Prevalence levels for Alzheimer disease and vascular dementia were also estimated., Results: Dementia prevalence by Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised ranged from 2.1% in men aged 71 through 74 years to 33.4% in men aged 85 through 93 years. Age-standardized prevalence was 7.6%. Prevalence estimates for the cohort were 9.3% for dementia (all cause), 5.4% for Alzheimer disease (primary or contributing), and 4.2% for vascular dementia (primary or contributing). More than 1 possible cause was found in 26% of cases. The Alzheimer disease/vascular dementia ratio was 1.5 for cases attributed primarily to Alzheimer disease or vascular dementia., Conclusions: Prevalence of Alzheimer disease in older Japanese-American men in Hawaii appears to be higher than in Japan but similar to European-ancestry populations. Prevalence of vascular dementia appears to be slightly lower than in Japan, but higher than in European-ancestry populations. Further cross-national research with emphasis on standardized diagnostic methods is needed.

The large number of participants (5,485 patients) in the Hypertension Detection and Follow-Up Program, Stepped Care, form the largest group to date on which detailed surveillance of long-term antihypertensive therapy and drug side effects has been reported. Over a five-year period, among all hypertensive persons (mild, moderate, and severe combined) who were not taking antihypertensive medications at the beginning of the study and who attended the clinic at least once during the five-year trial, a total of 9.3% had definite or probable side effects severe enough to cause discontinuation of the drug treatment in question. An additional 23.4% had drug treatment discontinued due to possible side effects. Within the mild, moderate, and severe hypertension categories, 8.6%, 11%, and 12%, respectively, had definite or probable side effects. The incidence of side effects declined over the five years in all race-sex groups. Five-year incidence of total side effects was 29.8% in those aged 60 to 69 years at entry and 38.0%, 36.8%, and 34.1%, respectively, in those aged 50 to 59, 40 to 49, and 30 to 39 years. Sexually related side effects required discontinuation of treatment in 8.3% of male participants. However, less than 1% of active participants required hospitalization for side effects. No death that could be attributed to side effects was detected. Thus, the Hypertension Detection and Follow-up Program data, which have previously demonstrated the beneficial effects of antihypertensive therapy, confirm the relative safety of such therapy.

At the conclusion of a double-blinded, randomized clinical trial of propranolol hydrochloride, but before unblinding, the patients and clinic personnel were asked to guess the treatment group assignment of each patient. While 79.9% of the patients receiving propranolol correctly identified their treatment group assignment, 57.2% of the patients receiving placebo incorrectly guessed that they were also in the propranolol group. No specific mechanism was identified to explain why more patients receiving propranolol were better able to guess their group assignment. Clinic physicians correctly identified the group assignment of 69.9% of the patients receiving propranolol and 68.8% of the patients receiving placebo. Clinic coordinators correctly identified the group assignment of 67.1% of the patients receiving propranolol and 70.6% of the patients receiving placebo. For clinic personnel, heart rate level and heart rate change seem to be the mechanisms employed to identify their patients' treatment assignment.

This study asks whether prolonged antihypertensive therapy will "cure" a substantial percent of rigorously treated hypertensive patients and whether nutritional change will add an antihypertensive effect and reduce the relapse rate. Of 584 eligible patients normotensive while receiving therapy, 496 were randomized into control and discontinued-medication groups with and without dietary intervention. At 56 weeks, 50% of those who were no longer receiving medication remained normotensive by study criteria. Randomization either to weight-loss group (mean loss of 4.5 kg [10 lb]) or to sodium-restriction group (mean reduction of 40 mEq/day) increased the likelihood of remaining without drug therapy, with an adjusted odds ratio of 2.17 for the sodium group and 3.43 for the weight group. Highest success rates were in the nonoverweight mild hypertensives with sodium restriction (78%) and the overweight mild hypertensives who were reducing their weight (72%). These data demonstrate that weight loss or sodium restriction, in hypertensives controlled for five years, more than doubles success in withdrawal of drug therapy.