Urinary sodium and potassium profile of blacks and whites in relation to education in two different geographic urban areas. TOMHS Research Group. Treatment of Mild Hypertension Study.

The high Na/low K environment of modern society is related to the genesis of hypertension and stroke. There is prior evidence of racial, geographical, and social class differences in Na and K intake and blood pressure. Baseline data from the Treatment of Mild Hypertension Study (TOMHS) was used to assess urinary Na and K excretion profiles by race, clinic geographic area, and education. Participants were adult black and white hypertensive patients from the Birmingham, Alabama, and Chicago, Illinois, area. Level of education was categorized as: less than college graduate and college graduate or more. Two overnight urine samples were collected and analyzed for Na and K at entry from 154 blacks and 281 whites. The urinary Na:K ratio was significantly higher in both blacks (5.1 v 3.8, P < .001) and whites (4.1 v 3.4, P < .005) in Birmingham compared with Chicago. This was primarily due to the lower excretion of urinary K in blacks (12.8 v 16.9 mmol/8 h, P < .01) and whites (14.0 v 16.5 mmol/8 h, P < .01). The highest urinary Na:K ratio was observed in blacks in Birmingham with lower education level; urinary Na excretion was high in blacks with a lower education level in both cities. No such differences were seen in whites. Although TOMHS was not population-based, these findings suggest the possibility that potassium intake among persons with stage 1 hypertension is related to geographic area in both blacks and whites, and sodium intake is inversely related to education level in blacks.

Community advisory boards: their role in AIDS clinical trials. Terry Beirn Community Programs for Clinical Research on AIDS.

Community-based AIDS research programs were initially federally funded in 1989. Since then, the Terry Beirn Community Programs for Clinical Research on AIDS has mandated that research units develop and maintain community advisory boards to provide advice and communicate community preferences in AIDS research. Seventeen community-based AIDS research units formed community advisory boards (CABs) based on a model developed by the Community Consortium at San Francisco General Hospital. Social workers employed by these AIDS research units surveyed 267 CAB members to ascertain board characteristics and members' perceptions of program activities. Implications for social work and future research are discussed.

Higher education and income are related to a better Na:K ratio in blacks: baseline results of the Treatment of Mild Hypertension Study (TOMHS) data.

In the United States, blacks have higher rates of hypertension than whites. A possible contributing factor to this higher rate of hypertension could be dietary differences between blacks and whites relating to sodium and potassium intake, which in turn could be related to socioeconomic differences between blacks and whites. Baseline data from the Treatment of Mild Hypertension Study (TOMHS) was used to assess differences in the urinary excretion of sodium and potassium, and the Na:K ratio between black and white participants, and also to explore the relationship of socioeconomic status (SES) and urinary electrolyte excretion within each ethnic group. Participants were men and women ages 45 to 69 with stage I diastolic hypertension (DBP < or = 99 mm Hg). Level of education and annual household income were used as indicators of SES. Two overnight urine samples were collected and analyzed for Na and K at entry on 172 black and 710 white participants. Blacks had a significantly higher mean Na:K ratio than whites, 4.3 v 3.6 (P < .001). This was primarily due to higher urinary Na excretion in blacks than whites, 57.8 v 52.7 mmol/8 h (P = .05). Analysis by education and income level showed that higher levels of urinary Na and Na:K in blacks than whites was restricted to those with lower education and income levels. For higher education and income levels, blacks had slightly lower levels of urinary Na and Na:K than whites. Correspondingly, education and income levels were related to urinary Na and Na:K in blacks but not in whites. This suggests that lower SES blacks could benefit from interventions to reduce dietary Na and increase dietary K, which would decrease their urinary Na:K ratio and may make them less prone to developing hypertension.

Proteinuria is a risk factor for mortality over 10 years of follow-up. MRFIT Research Group. Multiple Risk Factor Intervention Trial.

Proteinuria has been shown to be strongly associated with the prevalence and incidence of cardiovascular disease. It has been difficult to determine if the link is causal and independent. The mortality follow-up for the Multiple Risk Factor Intervention Trial (MRFIT) randomized cohort provides an opportunity to examine these relationships. Between 1973 and 1975, 361,662 men, ages 35 to 57, were screened for blood pressure, serum cholesterol, and cigarette smoking. Patients receiving medication for diabetes were excluded. Men in the upper 10 to 15% of coronary heart disease (CHD) risk (12,866) were randomized into the MRFIT trial. Standard casual urine dipstick determinations (Labstix) for protein were done at baseline and annually for six years. Post-trial cause-specific mortality was ascertained using the National Death Index. During the trial, 2326 (18.1%) of participants had + or higher proteinuria, and 593 (4.6%) had +2 or higher proteinuria. The presence of proteinuria during the six years of follow-up was consistently associated with higher all cause, cardiovascular disease (CVD) and CHD mortality, even after adjusting for other risk factors. The higher and more persistent the proteinuria, the greater the risk. In this data set, proteinuria is a strong and independent risk factor for CVD mortality.

Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions in mild hypertension.

Renal effects of mild hypertension and therapy have not been established. Since urinary albumin and N-acetyl-beta-D-glucosaminidase excretions reflect renal effects of hypertension, they were related to blood pressure, other cardiovascular risk factors, cardiac target organ effects, and response to therapy in mild hypertension (diastolic blood pressure 85-99 mm Hg). Participants were from two clinics of the Treatment of Mild Hypertension Study (TOMHS), a multicenter randomized, double-blind, controlled trial. Participants received nutritional-hygienic therapy and one of five active drugs or placebo. Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions were assessed prospectively using office "spot" collections from one clinic (n = 213) and retrospectively using overnight collections from the other clinic (n = 210). Relationships were determined between protein excretions and blood pressure, age, gender, race, blood glucose, cholesterol concentrations, and indices of body mass and left ventricular mass and function at baseline. Treatment effects were assessed after 3 to 12 months. Spot and overnight albumin excretions related positively to baseline systolic blood pressure by univariate analyses. Spot albumin excretion related positively to systolic blood pressure, age, creatinine clearance, and left ventricular function while overnight albumin excretion related positively to left ventricular mass and female gender by multiple regression analyses. Spot, but not overnight, albumin excretion declined significantly with active drug therapy. N-acetyl-beta-D-glucosaminidase excretion did not relate to blood pressure or decline with therapy. The combined results suggest albumin excretion correlates with blood pressure, decreases with antihypertensive drug therapy, and is associated with greater left ventricular function and mass, as well as glomerular filtration rate, even at mild levels of hypertension.

Cigarette smoking and mortality. MRFIT Research Group.

METHODS: The relationship of cigarette smoking and smoking cessation to mortality was investigated among men screened for and also among those randomized to the Multiple Risk Factor Intervention Trial (MRFIT). RESULTS: Among the 361,662 men screened for the MRFIT, cigarette smoking was an important risk factor for all-cause, coronary heart disease (CHD), stroke, and cancer mortality. These risks, on the log relative scale, were strongest for cancers of the lung, mouth, and larynx. The excess risk associated with cigarette smoking was greatest for death from CHD. Overall, approximately one-half of all deaths were associated with cigarette smoking. Among the 12,866 randomized participants, weak positive associations with duration of cigarette smoking habit and tar and nicotine levels were found with all-cause mortality. For both SI and UC men, substantial differences in subsequent CHD (34-49%) and all-cause (35-47%) mortality were evident for men who reported cigarette smoking cessation by the end of the trial compared with those continuing to smoke. There was no evidence that lung cancer death rates were lower among cigarette smokers who quite compared with those who continued to smoke in this 10-year follow-up period. CONCLUSION: The data are consistent with results of previous epidemiologic studies indicating that the benefits of smoking cessation on CHD are rapid, while for lung cancer, the benefit is not evident in a 10-year follow-up period.

The relationship of smoking cessation to coronary heart disease and lung cancer in the Multiple Risk Factor Intervention Trial (MRFIT).

The impact of smoking cessation on coronary heart disease (CHD) and lung cancer was assessed after 10.5 years of follow-up in the 12,866 men in the Multiple Risk Factor Intervention Trial (MRFIT). Those men who died of lung cancer (n = 119) were either cigarette smokers at entry or ex-smokers; no lung cancer deaths occurred among the 1,859 men who reported never smoking cigarettes. The risk of lung cancer for smokers, adjusted for selected baseline variables using a Cox proportional hazards model, increased as the number of cigarettes smoked increased (B = 0.0203, SE = 0.0076). There was not the same graded response for CHD among smokers at entry. The risk of CHD death was greater among smokers than nonsmokers (RR = 1.57) (B = -0.0034, S.E. = 0.0048). After one year of cessation, the relative risk of dying of CHD for the quitters as compared to non-quitters (RR = 0.63) was significantly lower even after adjusting for baseline differences and changes in other risk factors. The relative risk for smokers who quit for at least the first three years of the trial was even lower compared to non-quitters (RR = 0.38). However, the relative risk for lung cancer for quitters versus non-quitters was close to 1 both for quitters at 12 months and at three years. These data support the benefits of cessation in relation to CHD and are consistent with other epidemiologic studies which suggest that the lag time for a beneficial effect of smoking cessation on lung cancer may be as long as 20 years.

Relation of forced expiratory volume in one second (FEV1) to lung cancer mortality in the Multiple Risk Factor Intervention Trial (MRFIT).

For men participating in the Multiple Risk Factor Intervention Trial, the authors evaluated the relation between the baseline forced expiratory volume in one second and lung cancer mortality among smokers between the third and tenth years of follow-up (1973-1974 to 1984). This measure of ventilatory function was a powerful predictor of lung cancer deaths, with rates that increased from 3.02 per 1,000 person-years in the lowest quintile of forced expiratory volume to 0.43 in the highest quintile. This relation was not weakened by adjustments for smoking dose, including number of cigarettes smoked per day, tar and nicotine content, duration of smoking, or age at onset of smoking. Nor was forced expiratory volume related to time between its determination and lung cancer death. If these observations can be verified in other studies, the forced expiratory volume in one second may identify smokers at very high risk of lung cancer and, hence, in need of more aggressive preventive approaches.

The influence of oral potassium chloride on blood pressure in hypertensive men on a low-sodium diet.

Clinical and epidemiologic studies suggest that the intake of potassium chloride lowers blood pressure. To investigate whether supplemental potassium chloride (96 mmol of microcrystalline potassium chloride a day) reduced the need for antihypertensive medication in hypertensive men on a restricted-sodium diet, we conducted a randomized, placebo-controlled, double-blind clinical trial. A total of 287 men 45 to 68 years of age, 142 given potassium chloride and 145 given placebo, were followed for an average of 2.2 years after the withdrawal of their antihypertensive medication. Men in both groups received instructions on following a low-sodium diet. Overnight urinary sodium excretion fell from 63 mmol per eight hours at base line to an average of 45 mmol per eight hours during follow-up. Participants given supplemental potassium chloride had significantly higher (P less than 0.001) serum potassium levels and urinary potassium excretion (averaging 4.5 mmol per liter and 42.5 mmol per eight hours, respectively) during follow-up than participants given placebo (4.2 mmol per liter and 20.0 mmol per eight hours). Seventy-nine participants in each group required reinstitution of antihypertensive medication according to strict indications defined by the protocol. No significant differences in systolic or diastolic blood pressure were observed between the two groups. During follow-up, systolic and diastolic blood pressure averaged 130.6 and 82.5 mm Hg, respectively, for participants given supplemental potassium, and 132.5 and 83.1 mm Hg for participants given placebo. We conclude that supplemental potassium chloride does not reduce the need for antihypertensive medication in hypertensive men on a restricted-sodium diet.

An examination of the efficiency of some quality assurance methods commonly employed in clinical trials.

The cost and efficiency of training clinical centre staff and of duplicate data entry in clinical trials is reviewed. Training is an essential component of quality assurance programmes and it is usually carried out at regular intervals in long-term clinical trials. Initial training of staff and regular retraining is important to assure standardization and it can lead to reduced trial costs. Interim training for new staff and for remedial purposes is less efficient than regularly scheduled training sessions. Regional centres for training and the use of computer aided instruction are two ways such interim training can be made more efficient and standardized. Duplicate data entry or verification can result in a substantial reduction in data entry errors depending on the nature of the data being keyed. Selective verification should especially be considered for important fields for which consistency checks cannot be performed, that are alphabetic or that are several characters in length. Quality assurance procedures should be implemented to monitor data entry accuracy in clinical trials.

Effect of potassium supplementation combined with dietary sodium reduction on blood pressure in men taking antihypertensive medication.

It has long been suspected that sodium and potassium intake influence blood pressure. Since both these electrolytes can be modified by diet, attention has focused on decreasing sodium intake and increasing potassium intake as a potential way of treating and preventing hypertension. Several short-term controlled clinical trials have examined the effect of supplemental potassium intake on blood pressure, but with inconsistent results. The Minnesota Mount Sinai Hypertension Trial (MSHT) is a double-blind study comparing placebo with potassium supplementation for controlling blood pressure in hypertensive men on a sodium-restricted diet over a 2-3 year follow-up period. At the time of randomization to placebo or supplemental potassium and through 12 weeks of follow-up, the patients were taking antihypertensive medication. This preliminary report compares blood pressure changes between the placebo and supplemental potassium groups over the first 12 weeks of the trial.

Effects of passive smoking in the Multiple Risk Factor Intervention Trial.

The Multiple Risk Factor Intervention Trial (MRFIT), conducted in 1973-1982, provided a unique opportunity to study the effect of passive smoking on men whose wives smoke. MRFIT participants who reported at entry that they had never smoked tobacco products were classified according to the smoking status of their wives. Men with wives who smoked had similar mean levels of serum thiocyanate (54.3 vs. 53.9 mumol/liter, p = 0.83) but higher mean levels of expired carbon monoxide (7.7 vs. 7.1 ppm, p = 0.001). Lower levels of pulmonary function (by maximum forced expiratory volume in one second) were also observed in these men (3,493.1 vs. 3,591.9 ml, p = 0.04). The relative risks, for men whose wives smoked compared with men whose wives did not smoke, for the endpoints coronary heart disease death, fatal or nonfatal coronary heart disease event, and death from any cause were 2.11 (p = 0.19, 95% confidence interval (CI) 0.69-6.46), 1.48 (p = 0.13, 95% CI 0.89-2.47), and 1.96 (p = 0.08, 95% CI 0.93-4.11), respectively. When smokers who quit prior to entry were included in the analyses, the relative risks, for men whose wives smoked compared with men whose wives did not smoke, for the above endpoints were 1.45 (p = 0.25, 95% CI 0.77-2.73), 1.19 (p = 0.29, 95% CI 0.85-1.65), and 1.72 (p = 0.01, 95% CI 1.12-2.64), respectively. These relative risk estimates did not change appreciably after adjusting for other baseline risk factors. The results suggest that passive exposure to cigarette smoke may have a deleterious impact on the health of nonsmokers and that nonsmokers may be at an increased risk of death through passive exposure to cigarette smoke.

A new clamping and stretching procedure for determination of collagen fiber stiffness and strength relations upon maturation.

Clamping of tendon fibers is a major concern in connective tissue biomechanics. We present here a new clamping method. Also the stretching procedure is different from the conventional extension until the point of failure. Thus we have used a procedure of interval stretches, where 0.01 extensions during 2.5 s are succeeded by periods of relaxation. This procedure reduces the stress on clamps and transducers which causes serious problems in conventional extensions of some older specimen. The influence of stretching rate and periods of relaxation on the observed values of stiffness has been tested and discussed. The fibers from rat tail tendons only show a minor increase in stiffness between 40 day and 90 day old animals, and do not show significant changes from the age of 90 to 240 days. The values of stiffness expressed as Young's modulus of elasticity, had maximal values of 1.2, 1.8 and 1.9 kNmm-2 at the three ages investigated. The fiber strength, however, increases dramatically, thus the ultimate value was 18 Nmm-2 for 40 day old fibers, while at 90 days and 240 days it had increased to 102 Nmm-2 and to 106 Nmm-2, respectively.

X-ray diffraction evidence of collagen molecular packing and cross-linking in fibrils of rat tendon observed by synchrotron radiation.

X-ray diffraction patterns of fibres from 90 day (mature) rat-tail tendons were investigated using synchrotron radiation. The specimens were kept isometric at their corresponding in vitro rest length, and effects of pH and ionic strength were studied during short X-ray exposures. The results indicate that fibrils, equilibrated in physiological Ringer prior to exposure, have segregated lateral regions of well ordered collagen molecular packing. Lowering the ionic strength or the pH to 4.0 causes an order/disorder transition during which the fibril crystallinity decreases. At pH 3.5 a dramatic increase in the lateral swelling was observed. This effect was absent for fibres pretreated with sodium borohydride. The results are interpreted on the basis of cross-linking phenomena whereby the aldimine cross-link seems to be a controlling component of the lateral packing arrangement of collagen molecules.