Brain natriuretic peptide and insulin resistance in older adults.

AIMS: Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. METHODS: N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. RESULTS: Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). CONCLUSIONS: In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.

Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study.

BACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy. METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (

Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study.

The effect on 7 year survival of having a normal or near normal coronary arteriogram was examined using data from the CASS registry of 21,487 consecutive coronary arteriograms taken in 15 clinical sites. Of these, 4,051 arteriograms were normal or near normal, and the patients had normal left ventricular function as judged by absence of a history of congestive heart failure, no reported segmental wall motion abnormality and an ejection fraction of at least 50%; 3,136 arteriograms were entirely normal and the remaining 915 revealed mild disease with less than 50% stenosis in one or more segments. The 7 year survival rate was 96% for the patients with a normal arteriogram and 92% for those whose study revealed mild disease (p less than 0.0001). Nine risk variables recorded at entry were analyzed for predictive value for survival: age, sex, height, weight, history of smoking, presence of absence of mild disease, electrocardiographic response to exercise, family history of coronary heart disease and a history of hypertension. Of these, age, smoking history, presence or absence of disease and a history of hypertension had predictive value.

Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators.

BACKGROUND AND OBJECTIVES: The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined. This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study, a randomized clinical trial comparing warfarin, aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation. METHODS: Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents. The relative risk of cardiac mortality, including arrhythmic death, in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors. RESULTS: In patients receiving antiarrhythmic drug therapy, cardiac mortality was increased 2.5-fold (p = 0.006, 95% confidence interval [CI] 1.3 to 4.9) and arrhythmic death was increased 2.6-fold (p = 0.02, 95% CI 1.2 to 5.6). Among patients with a history of congestive heart failure, those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 (p less than 0.001, 95% CI 1.9 to 11.6) compared with that of patients not so treated; the relative risk of arrhythmic death in the treated group was 3.7 (p = 0.01, 95% CI 1.3 to 10.4). Patients without a history of congestive heart failure had no increased risk of cardiac mortality (relative risk 0.70, 95% CI 0.2 to 3.1) during antiarrhythmic drug therapy. After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death, patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death. However, in patients with a history of heart failure who received antiarrhythmic drug therapy, the relative risk of cardiac death was 3.3 (p = 0.05, 95% CI 0.99 to 11.1) and that of arrhythmic death was 5.8 (p = 0.009, 95% CI 1.5 to 21.7) compared with the risk in patients not taking antiarrhythmic medications. CONCLUSIONS: Although antiarrhythmic drug therapy was not randomly determined in this trial, the data suggest that in patients with atrial fibrillation and a history of congestive heart failure, the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm.

Coronary Artery Surgery Study (CASS): comparability of 10 year survival in randomized and randomizable patients.

The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial.

Anomalous coronary arteries: location, degree of atherosclerosis and effect on survival--a report from the Coronary Artery Surgery Study.

Limited information is available about clinical presentation, degree of atherosclerosis and effect on overall survival in a large series of patients with coronary artery anomalies. From the National Heart, Lung, and Blood Institute Multicenter Coronary Artery Surgery Study (CASS), detailed coding of coronary angiograms was available in 24,959 patients. Of these patients, 73 (0.3%) had major coronary artery anomalies: 70 had one coronary anomaly and 3 had two coronary anomalies. The most common anomaly involved the circumflex coronary artery (60%). In 69% of these, the circumflex artery arose from a separate ostium in the right coronary sinus, and in 31% it originated as a branch of the right coronary artery. The most common anomalous course was anterior or posterior to the great vessels but not between the great vessels. The major exception to this finding was an anomalous right coronary artery; 7 of 15 such arteries coursed between the great vessels. Anomalous circumflex coronary arteries had a significantly greater degree of stenosis than that in nonanomalous arteries in age- and gender-matched control patients (p = 0.02). Despite this difference, at 7 years there was no significant difference in survival by location or degree of stenosis in the anomalous artery.

Modifiable risk factors for incident heart failure in the coronary artery surgery study.

BACKGROUND: Even with aggressive treatment, heart failure is associated with a substantial morbidity and mortality. This poor prognosis has led to increasing interest in primary prevention, and the identification of modifiable risk factors. Our objective was to determine whether modifiable cardiovascular risk factors, including systolic and diastolic blood pressure, fasting glucose level, cholesterol level, weight, and smoking, were independent risk factors for heart failure in patients with anatomically confirmed coronary artery disease. METHODS: We studied all patients with documented coronary artery disease eligible for the multicenter, randomized-controlled Coronary Artery Surgery Study. After excluding 79 prevalent cases, we identified incident cases of heart failure using hospital discharge abstracts, mortality records, or self-reported follow-up questionnaires. Criteria for self-reported cases were treatment with digitalis and/or furosemide plus two or more heart failure symptoms, including dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, or edema. Cox regression analysis was used to estimate adjusted relative risks. RESULTS: At 12-year follow-up, the cumulative incidence of heart failure was 20.6%. Smoking (relative risk, 1.47) and weight (relative risk, 1.15/10 kg) were independently associated with incident heart failure. Myocardial infarction during follow-up, age, female sex, and baseline left ventricular dysfunction were also risk factors for heart failure. CONCLUSIONS: Patients with stable coronary artery disease are at high risk for developing heart failure, especially following myocardial infarction. However, interventions aimed at smoking cessation and weight reduction may prevent clinical heart failure in these patients.

Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data.

OBJECTIVE: To evaluate the relationship between serum cholesterol level and all-cause, coronary heart disease (CHD), and non-CHD mortality as a function of age. METHODS: The data source was the biennial examination data from 1948 through 1980 for the 5209 men and women enrolled in the Framingham Heart Study. Age-specific analyses by the Cox proportional hazards regression model were performed of survival subsequent to ages 40, 50, 60, 70, and 80 years for all subjects enrolled and alive at each of the stated ages. Complementary models were studied that used high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or total cholesterol level as predictors of survival subsequent to the examination at which lipoprotein subfractions were determined (1968) through 1973). RESULTS: The relationship between total cholesterol level and all-cause mortality was positive (ie, higher cholesterol level associated with higher mortality) at age 40 years, negative at age 80 years, and negligible at ages 50 to 70 years. The relationship with CHD mortality was significantly positive at ages 40, 50, and 60 years but attenuated with age until the relationship was positive, but not significant, at age 70 years and negative, but not significant, at age 80 years. Results for the relationship between low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and mortality help explain these findings. Non-CHD mortality was significantly negatively related to cholesterol level for ages 50 years and above. The negative results in the oldest age group for all-cause and CHD morality appeared to be due to a negative relationship with low-density lipoprotein cholesterol levels rather than the protective effect of high high-density lipoprotein cholesterol levels. Similar results from several modified analyses make low cholesterol level due to severe illness an unlikely explanation for our results. CONCLUSIONS: Physicians should be cautious about initiating cholesterol-lowering treatment in men and women above 65 to 70 years of age. Only randomized clinical trials in older people can settle the debate over the efficacy and cost-effectiveness of lipid-lowering interventions for reducing mortality and morbidity in this population.

Coronary artery disease in diabetic patients with lower-extremity arterial disease: disease characteristics and survival. A report from the Coronary Artery Surgery Study (CASS) registry.

OBJECTIVE: Patients who have diabetes and lower-extremity arterial disease (LEAD) are at an increased risk of dying from coronary artery disease (CAD). This study was undertaken to: 1) define the clinical and arteriographic factors associated with LEAD among diabetic patients; 2) determine the long-term survival and predictors of mortality of diabetic patients with LEAD, compared to those without LEAD; and 3) determine if the presence of LEAD is an independent risk factor for mortality among diabetic patients with CAD. RESEARCH DESIGN AND METHODS: A total of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry with LEAD, who were > or = 50 years of age, and who had arteriographically proven CAD, were identified and followed for a mean of 12.8 years. A total of 1,349 comparably aged diabetic patients from the CASS registry with CAD and no evidence of LEAD were followed for an equivalent period of time. RESULTS: Compared with diabetic patients without LEAD, diabetic patients with LEAD were characterized by the presence of cerebrovascular disease, a high rate of current smoking, elevated systolic blood pressure, high grades of angina pectoris, and digitalis use. Severity of epicardial CAD and extent of CAD were not independent predictors of the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly higher mortality (mostly cardiovascular) than diabetic patients without LEAD, with a median survival of 8.1 and 10.9 years, respectively. On multivariate analysis, age, the number of significantly narrowed coronary arteries, and the presence of left ventricular dysfunction predicted mortality in both subsets of diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD was an independent risk factor for mortality. CONCLUSIONS: Diabetic patients with LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients without LEAD, despite no apparent anatomic differences in the severity and extent of CAD. This suggests that factors associated with the presence of LEAD, other than the anatomy of the coronary circulation, may play a role in determining survival among diabetic patients with LEAD and CAD.

The cystic fibrosis therapeutics development network (CF TDN): a paradigm of a clinical trials network for genetic and orphan diseases.

Clinical trials have become critical to the advancement of medical science and to the evolution of patient care in medicine. The science of clinical research has advanced from early studies in which treatment was assessed without controls to sophisticated multinational collaborative randomized, double-blind, placebo controlled trials of therapeutic interventions. To facilitate the advancement of clinical research, clinical trials networks have been developed to conduct multicenter studies. This review describes the history of clinical trials, clinical trials networks, and the goals of such networks in the United States. The Cystic Fibrosis Therapeutics Development Network, a network that represents the paradigm for genetic and orphan diseases, is described in detail. This network has been extremely successful in its first 3.5 years of existence conducting 18 different clinical trials in patients with Cystic Fibrosis. Unique aspects of the network include the use of internet applications for study conduct and communication, the development of statistical methodology to enhance the efficiency of clinical trial design, the development of outcome measures specific to Cystic Fibrosis, and the development of infrastructure necessary for expediting protocol development. In the current environment, clinical research faces significant challenges related to ensuring the safe and ethical conduct of clinical research while promoting fast and efficient clinical trials. To succeed and move forward to provide treatments and find cures for diseases, clinical trials networks must continue to evolve. The Cystic Fibrosis Therapeutics Development Network represents a network that has met this challenge and will continue to provide a venue for the safe and efficient conduct of clinical trials in Cystic Fibrosis.

Properties of the random zero sphygmomanometer.

The random zero sphygmomanometer is widely used in studies involving blood pressure measurement because it is believed to eliminate digit preference and reduce measurement error. We performed blood pressure measurements sequentially using random zero and standard sphygmomanometers in random order in 1,356 participants in the Cardiovascular Health Study. Despite adherence to the manufacturer's instructions, we observed a substantially nonuniform distribution of zero levels generated by the random zero sphygmomanometer and a disturbing correlation between the zero level and blood pressures taken with the standard sphygmomanometer. With the random zero device, the pooled estimated slopes for the regression of standard systolic and diastolic pressures on the zero level were -0.71 and -0.17, respectively (both p < 0.0001). The only plausible explanation for this relation between the random zero device and the standard device is that by some unknown mechanism the subject's blood pressure is influencing the zero level. Systolic and diastolic blood pressures measured with the random zero device were, respectively, 1.65 and 1.84 mm Hg lower (both p < 0.0001) than standard blood pressures. Digit preference was detectable in the uncorrected blood pressure and zero level measured with the random zero device but was eliminated after calculation of the corrected blood pressure. For most epidemiological studies, the random zero sphygmomanometer offers no significant advantage over the standard sphygmomanometer. It may still be useful in those epidemiological studies and clinical trials where blinding is important.

Correlates of blood pressure in community-dwelling older adults. The Cardiovascular Health Study. Cardiovascular Health Study (CHS) Collaborative Research Group.

Although elevated blood pressure is an important predictor of cardiovascular disease and stroke in the elderly, little information exists on the distribution and risk factor correlates of blood pressure in this group. As part of the Cardiovascular Health Study, a population-based cohort study of 5201 men and women aged 65 to 101 years, we investigated correlates of systolic and diastolic blood pressure. Multiple regression analyses were conducted for all participants and a subgroup of 2482 without coronary heart disease and not on antihypertensive therapy (the "healthier" subgroup). In the total group, independent predictors of diastolic blood pressure included heart rate, aortic root dimension, creatinine, hematocrit, alcohol use, and black race (positive associations) and internal carotid artery wall thickness, mitral early/late peak flow velocity, white blood cell count, cigarette smoking, and age (negative associations). Positive predictors of systolic blood pressure included mitral late peak flow velocity, left ventricular mass, common carotid artery wall thickness, serum albumin, factor VII, diabetes, alcohol use, and age; negative predictors were coronary heart disease, uric acid, height, and smoking. In the healthier subgroup, positive predictors of diastolic blood pressure included heart rate, hematocrit, serum albumin, creatinine, and body weight, whereas mitral early/late peak flow velocity, serum potassium, smoking, and age inversely related to diastolic pressure. For the same group, common carotid artery wall thickness, left ventricular mass, serum albumin, factor VII, high-density lipoprotein cholesterol, and age were directly related to systolic blood pressure, whereas serum potassium was inversely related. Both systolic and diastolic pressures varied considerably by geographic site.(ABSTRACT TRUNCATED AT 250 WORDS)

Natural history of Giardia infection of infants and children in rural Guatemala and its impact on physical growth.

Longitudinal data on Giardia excretion, diarrheal disease, and physical growth during the first 3 yr of life collected more than 20 yr ago in 45 Guatemalan children were analyzed. This report describes the natural history of this infection and estimates its effects on growth. All children had at least one Giardia infection, prevalence and incidence rates reaching 20.2% and 5.3%, respectively by the end of the third year. The mean number of Giardia infections per child increased from 0.7 in the first to 3.6 in the third year. More than 40% of these infections lasted 2-6 wk or more and were commonly associated with diarrhea. Weight velocity was significantly lower in the second year of life in Giardia-infected than in Giardia-negative children (p = 0.03). The duration of Giardia episodes and their association with diarrhea appeared to be the most important factors associated with growth disturbance. Although simultaneous infection with other enteropathogens occurred in many children, our findings suggest that Giardia infection may have independent deleterious effects on children's growth.

PIP: Longitudinal data on Giardia excretion, diarrheal disease, and physical growth during the 1st 3 years of life collected more than 20 years ago in 45 Guatemalan children were analyzed. This report describes the natural history of this infection and estimates its effects on growth. All children had at least 1 Giardia infection, prevalence and incidence rates reaching 20.2% and 5.3%, respectively by the end of the 3rd year. The mean number of Giardia infections per child increased from 0.7 in the 1st year to 3.6 in the 3rd year. More than 40% of these infections lasted 2-6 weeks or more and were commonly associated with diarrhea. Weight velocity was significantly lower in the 2nd year of life in Giardia-infected than in Giardia-negative children (p=0.03). The duration of Giardia episodes and their association with diarrhea appeared to be the most important factors associated with growth disturbance. Although simultaneous infection with other enteropathogens occurred in many children, the findings suggest that Giardia infection may have independent deleterious effects on children's growth.

The impact of Haemophilus influenzae type b meningitis on nutritional status.

We investigated the immediate impact and long-term effects of Haemophilus influenzae type b meningitis on nutritional status and growth in 111 children. Mean weight change during 10 d of hospitalization was a loss of less than 1%. Follow-up median weight-for-height percentiles increased after admission (p less than 0.01). Percentile values were as follows: admission, 45th; 1 mo, 60th; 3 mo, 60th; and 6 mo, 68th. Forty-three percent of the cases were greater than 75th percentile of weight-for-height at 6 mo after disease. An additional follow-up assessment of weight-for-height indicated that 43% of a representative sample subset of 49 were still obese 1.17-5.5 y after disease. Significant differences in median concentrations of serum prealbumin were found between days 1 (128 mg/L) and 5 (199 mg/L, p less than 0.0001) and days 5 and 10 (214 mg/L, p less than 0.02). Median erythrocyte glutathione reductase activity coefficients increased between days 1 (1.16) and 5 (1.20, p less than 0.01). The mean free erythrocyte protoporphyrin-heme ratio increased between days 5 (10.78 X 10(-6)) and 10 (14.22 X 10(-6), p less than 0.01). We conclude that there were transient adverse changes in nutritional status. Obesity appears to occur after disease.

High body fatness, but not low fat-free mass, predicts disability in older men and women: the Cardiovascular Health Study.

Using data from the Cardiovascular Health Study, we studied the relation between body composition (fat mass and fat-free mass, assessed by bioelectrical impedance) and self-reported, mobility-related disability (difficulty walking or stair climbing) in 2714 women and 2095 men aged 65-100 y. In a cross-sectional analysis at baseline (1989-1990), disability was reported by 26.5% of the women and 16.9% of the men. A positive association was observed between fat mass and disability. The odds ratio for disability in the highest quintile of fat mass was 3.04 (95% CI: 2.18, 4.25) for women and 2.77 (95% CI: 1.82, 4.23) for men compared with those in the lowest quintile. Low fat-free mass was not associated with a higher prevalence of disability. In a longitudinal analysis among persons not reporting disability at baseline, 20.3% of the women and 14.8% of the men reported disability 3 y later. Fat mass at baseline was predictive of disability 3 y later, with odds ratios of 2.83 (95% CI: 1.80, 4.46) for women and 1.72 (95% CI: 1.03, 2.85) for men in the highest quintile of fat. The increased risk was not explained by age, physical activity, chronic disease, or other potential confounders. Low fat-free mass was not predictive of disability. The results showed that high body fatness is an independent predictor of mobility-related disability in older men and women. These findings suggest that high body fatness in old age should be avoided to decrease the risk of disability.

Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses.

BACKGROUND: Aspirin therapy reduces stroke by about 25% for persons with atherosclerotic vascular disease, but the effect in those without clinically apparent vascular disease is distinctly different. OBJECTIVE: To define the effect of aspirin use on stroke and other major vascular events when given for primary prevention to persons without clinically recognized vascular disease. DATA SOURCES AND EXTRACTION: Systematic review of randomized clinical trials and large prospective observational cohort studies examining the relation between aspirin use and stroke in persons at low intrinsic risk. Studies were identified by a computerized search of the English-language literature. DATA SYNTHESIS: Five randomized trials of primary prevention included 52 251 participants randomized to aspirin doses ranging from 75 to 650 mg/d; the mean overall stroke rate was 0.3% per year during an average follow-up of 4.6 years. Meta-analysis revealed no significant effect on stroke (relative risk = 1.08; 95% confidence interval, 0.95-1.24) contrasting with a decrease in myocardial infarction (relative risk = 0.74; 95% confidence interval, 0.68-0.82). The lack of reduction of stroke by aspirin for primary prevention was incompatible with its protective effect against stroke in patients with manifest vascular disease (P = .001). Intracranial hemorrhage was increased by the regular use of aspirin (relative risk = 1.35; P = .03), similarly for both primary and secondary prevention. In 4 large observational studies, self-selected use of aspirin was consistently associated with higher rates of stroke. CONCLUSIONS: The effect of aspirin therapy on stroke differs between individuals based on the presence or absence of overt vascular disease, in contrast with the consistent reduction in myocardial infarction by aspirin therapy observed in all populations. We hypothesize that the effect of aspirin therapy on stroke for persons with major risk factors for vascular disease may be intermediate between a substantial decrease for those with manifest vascular disease and a possible small increase for healthy persons due to accentuated intracranial hemorrhage. When aspirin is given for primary prevention of vascular events, available data support using 75 to 81 mg/d.

Serum potassium level and dietary potassium intake as risk factors for stroke.

BACKGROUND: Numerous studies have found that low potassium intake and low serum potassium are associated with increased stroke mortality, but data regarding stroke incidence have been limited. Serum potassium levels, dietary potassium intake, and diuretic use in relation to risk for stroke in a prospectively studied cohort were investigated. METHODS: The study comprised 5,600 men and women older than 65 years who were free of stroke at enrollment. Baseline data included serum potassium level, dietary potassium intake, and diuretic use. Participants were followed for 4 to 8 years, and the incidence and types of strokes were recorded. Low serum potassium was defined as less than 4.1 mEq/L, and low potassium intake as less than 2.4 g/d. RESULTS: Among diuretic users, there was an increased risk for stroke associated with lower serum potassium (relative risk [RR]: 2.5, p < 0.0001). Among individuals not taking diuretics, there was an increased risk for stroke associated with low dietary potassium intake (RR: 1.5, p < 0.005). The small number of diuretic users with lower serum potassium and atrial fibrillation had a 10-fold greater risk for stroke compared with those with higher serum potassium and normal sinus rhythm. CONCLUSIONS: A lower serum potassium level in diuretic users, and low potassium intake in those not taking diuretics were associated with increased stroke incidence among older individuals. Lower serum potassium was associated with a particularly high risk for stroke in the small number of diuretic users with atrial fibrillation. Further study is required to determine if modification of these factors would prevent strokes.

Relation of hemodynamics and risk factors to ventricular-vascular interactions in the elderly: the Cardiovascular Health Study.

OBJECTIVE: To investigate the interaction between left ventricular (LV) geometry, carotid structure and arterial compliance in relation to hemodynamic stimuli and risk factors (plasma cholesterol, body mass index, insulin resistance, smoking habit, age, sex and race). DESIGN: Cross-sectional. METHODS: Echocardiography and carotid ultrasound were performed in 2375 elderly subjects without signs or history of prevalent cardiovascular disease, diabetes or renal disease (795 men; 298 non-whites; 1215 hypertensive), from the cohort of the Cardiovascular Health Study. Arterial compliance was estimated by the prognostically validated ratio of stroke volume to pulse pressure (SV/PP) as the percent deviation (Delta%) from the value predicted by individual age, heart rate and body weight. RESULTS: Intima-medial thickness (IMT) was higher in the presence of LV hypertrophy (LVH) in normotensive and hypertensive subjects and was greatest in the presence of concentric LVH. Maximum carotid lumen diameter (CLD) was also higher in the presence of LVH (and was greatest with eccentric LVH, in association with relatively high values for stroke volume). After adjusting for blood pressure, maximum carotid lumen diameter was directly correlated with stroke volume, and IMT to LV mass (all P < 0.001). Similarly, IMT was also related to maximum carotid lumen diameter, independently of prevalent risk factors (P < 0.001). SV/PP-Delta% was reduced in both groups with concentric LV remodeling (both P < 0.0001) or concentric LVH (both P < 0.05). Adjusting for risk factors did not affect these associations in normotensives, but made them insignificant in hypertensives. In normotensives, IMT was inversely related to SV/PP-Delta% (P < 0.001), independently of risk factors, whereas no significant relation was found in hypertensives. CONCLUSIONS: The magnitudes of carotid intima-medial thickness and lumen diameter parallel levels of LV mass and geometry, and are directly related to stroke volume and arterial stiffness; this interaction is most evident in the presence of normal blood pressure, whereas it is affected by other cardiovascular risk factors when arterial hypertension is present.

Physical growth in phenylketonuria: II. Growth of treated children in the PKU collaborative study from birth to 4 years of age.

Height, weight, and head circumference data up to age 4 years are reported for 124 children with phenylketonuria (PKU) who had been started on diet management before 4 months (121 days) of age and who were participating in the Collaborative Study of Children Treated for Phenylketonuria. Growth measurements of both the children and their parents corresponded with national and international standards. The growth of children with PKU was compared also with that of a group of normal children in the United States in whom corresponding longitudinal growth data had been obtained at the Fels Research Institute (FRI). Statistically significant differences betweeen the groups were not noted at any age. However, when these groups were compared on coefficients using curve fitting, a trend toward a greater increase in weight as they became older, noted in both sexes in the PKU study group, was significantly higher (P less than .005) in the PKU study girls compared with the FRI sample. Height growth was identical in both groups, and comparison with family data showed that the children with PKU grew as expected for their genetic endowment.

Randomized trial of silver nitrate, erythromycin, and no eye prophylaxis for the prevention of conjunctivitis among newborns not at risk for gonococcal ophthalmitis. Eye Prophylaxis Study Group.

OBJECTIVE: To compare the efficacy of commonly used forms of eye prophylaxis for newborns with no prophylaxis in the prevention of nongonococcal conjunctivitis. DESIGN: Randomized doubly masked clinical trial. SETTING: University of Washington Hospital and affiliated clinics, Seattle, between 1985 and 1990. SUBJECTS: The medical records of 8499 women were evaluated for possible participation; 2577 were eligible. Of the 758 enrolled, the infants of 630 were evaluable. INTERVENTION: Comparison of silver nitrate, erythromycin, and no eye prophylaxis given at birth for the prevention of conjunctivitis. MAIN OUTCOME MEASURES: Conjunctivitis during the first 60 days of life and nasolacrimal duct patency in the first 2 days of life. RESULTS: The frequency of impatent tear ducts at the 30- to 48-hour examination did not differ significantly by prophylaxis group. Among the 630 infants randomized and observed, 109 (17%) developed mild conjunctivitis. Sixty-nine (63%) of the cases appeared during the first 2 weeks of life. After 2 months of observation, infants allocated to silver nitrate eye prophylaxis at birth had a 39% lower rate of conjunctivitis (hazard ratio = 0.61, 95% confidence interval = 0.39 to 0.97), and those allocated to erythromycin had a 31% lower rate of conjunctivitis (hazard ratio = 0.69, 95% confidence interval = 0.44 to 1.07), than did those allocated to no prophylaxis. CONCLUSION: Silver nitrate eye prophylaxis caused no sustained deleterious effects and even provided some benefit to infants born to women without Neisseria gonorrhoeae. However, the effect was modest and against microorganisms of low virulence. The results suggest that parental choice of a prophylaxis agent including no prophylaxis is reasonable for women receiving prenatal care and who are screened for sexually transmitted diseases during pregnancy.