An evaluation of the intervention against smoking in the multiple risk factor intervention trial

The results of the Multiple Risk Factor Intervention Trial showed no significant difference in mortality from coronary heart disease between intervention and control groups despite an apparent success of the intervention against cigarette smoking. A reanalysis of the published data indicates that the effectiveness of the smoking intervention may have been overestimated. The researchers counted those who smoked pipes or cigars at screen as nonsmokers and attempted to classify cigarette smokers who switched to pipes or cigars during the trial as successes whether or not they continued to inhale the smoke. It is unreasonable to assume a priori that inhaling pipe or cigar smoke is less dangerous than cigarette smoke. Moreover, attempting to include pipe and cigar smokers, who may have been inhaling smoke, among the successes makes biochemical validation of claims of abstinence overly lenient. When levels of serum thiocyanate are used to obtain an objective index of smoking reduction, it appears that the effect of intervention was considerably smaller than has been reported, and failed to reach design goals over the first 4 years. This could help to explain the disappointing mortality results.     

Relationship between baseline risk factors and coronary heart disease and total mortality in the multiple risk factor intervention trial

The relationship between selected baseline risk factors and subsequent coronary heart disease (CHD) death and total mortality among participants in the Multiple Risk Factor Intervention Trial (MRFIT) was studied in order to determine (a) whether the three risk factors used to identify high-risk men for the trial were associated with CHD death; (b) whether other risk factors measured at baseline, especially lipoprotein cholesterol levels, were associated with CHD and total mortality; and (c) whether there were any differences between special intervention (SI) and usual care (UC) participants in the relationship of the specific levels of risk factors to CHD or total mortality. The three main risk factors (blood cholesterol, cigarette smoking, and diastolic blood pressure) and age were significantly associated with CHD mortality; age, diastolic blood pressure, and cigarette smoking were associated with total mortality. The risk score based on the multiple logistic equation developed from the Framingham Study was also strongly associated with CHD mortality. When the joint associations of selected baseline risk factors with CHD and total mortality were considered, age, diastolic blood pressure, cigarette smoking, and low- and high-density lipoprotein cholesterol were significantly associated with CHD mortality; age, cigarette smoking, and low-density lipoprotein cholesterol were positively associated with total mortality. Systolic blood pressure significantly improved the prediction of CHD mortality for SI and UC men when it was added to a regression model that included age, diastolic blood pressure, cigarettes smoked per day, body mass index, and lipoprotein levels, but improved the prediction of total mortality only for SI men. In similar analyses, serum thiocyanate improved the prediction of both CHD and total mortality for UC men. Among SI men the improved prediction gained by considering serum thiocyanate was less pronounced and not significant for CHD death. This latter finding may be due in part to the changes made in smoking behavior by SI participants during the course of the study. The estimated regression coefficients for CHD and total mortality endpoints were not significantly different between the SI and UC groups.     

The multiple risk factor intervention trial (MRFIT): I. Historical perspectives

The beginnings of the Multiple Risk Factor Intervention Trial (MRFIT) for the primary prevention of coronary heart disease (CHD) are chronicled. Over the period 1960–1970, various scientific panels had urged the undertaking of primary CHD prevention trials but with limited consensus on the specific type of study needed. The Task Force on Arteriosclerosis convened by the National Heart and Lung Institute (NHLI) in 1971 recommended that a national diet-heart trial not be supported but, instead, that the NHLI undertake multiple risk factor intervention trials in individuals at high risk of CHD due to combinations of elevated serum lipids, hypertension, and cigarette smoking. Late in 1971, the NHLI invited proposals for MRFIT. Its primary purpose was to determine whether a special risk factor intervention program directed at the reduction of elevated serum cholesterol, elevated diastolic blood pressure, and cigarette smoking in men at high risk of death from CHD (but still free of clinical evidence of CHD) would result in a significant reduction in CHD mortality; nonfatal myocardial infarction or CHD mortality; cardiovascular mortality; and mortality from all causes—over a 6-year period. In 1972–1973, funds to conduct such a study among 12,000 randomized men were awarded to 22 clinical centers, a coordinating center, central laboratory, standardization laboratory, ECG centers, and a drug distribution center. The evolution of the organization of this research undertaking is described.     

Feasibility and acceptability of a multiple risk factor intervention: The Step Up randomized pilot trial

Background  

Interventions are needed which can successfully modify more than one disease risk factor at a time, but much remains to be learned about the acceptability, feasibility, and effectiveness of multiple risk factor (MRF) interventions. To address these issues and inform future intervention development, we conducted a randomized pilot trial (n = 52). This study was designed to assess the feasibility and acceptability of the Step Up program, a MRF cognitive-behavioral program designed to improve participants' mental and physical well-being by reducing depressive symptoms, promoting smoking cessation, and increasing physical activity.     

The multiple risk factor intervention trial (MRFIT). VII. A comparison of risk factor changes between the two study groups

Risk factor changes over 4 years for MRFIT Special Intervention (SI) participants are compared with risk factor changes made by Usual Care (UC) participants. Differences between the two study groups are compared with original design assumptions. After 4 years of follow-up, serum cholesterol differences averaged 50% of what was predicted; diastolic blood pressure differences between the two study groups averaged 67% of that predicted; cigarette smoking reductions in the Special Intervention group relative to the Usual Care group have exceeded what was predicted each year based on reported histories. When serum thiocyanate is used to verify reported cessation the SI-UC difference is reduced but still averages greater than the reductions predicted in the third and fourth years of follow-up.     

The multiple risk factor intervention trial (MRFIT): V. Intervention on smoking

The development, implementation, and results of the smoking cessation program of the Multiple Risk Factor Intervention Trial (MRFIT) are presented. The MRFIT is a 6-year clinical trial designed to investigate the effects of reducing cardiovascular risk factors—elevated cholesterol, hypertension, and cigarette smoking—in a group of asymptomatic men at high risk of cardiovascular disease. The men participated in an integrated intervention program that offered both group and individual formats, a structured maintenance program for those who stopped smoking, and an extended intervention program for those unable to quit initially. Results among the original 4,103 smokers included a 47.3% quit rate 4 months after program initiation and a 45.9% quit rate after 4 years. Of those reporting no smoking at 4 months, 56% were abstinent at all visits through 48 months. Most recidivism occurred soon after initial cessation, with 17% of the men who reported quitting at 4 months reporting smoking 4 months later. The quit rates were strongly associated with the initial level of smoking, with light smokers reporting higher quit rates and lower recidivism rates at all visits through 4 years. Results exceed trial goals whether measured by self-reports or by thiocyanate levels, an objective assessment of smoking behavior. Discussion focuses on understanding the variables contributing to smoking cessation and to achieving the goals of reduction of risk of cardiovascular disease.     

The multiple risk factor intervention trial (MRFIT).: II. The development of the protocol

The detailed development of the MRFIT protocol is discussed, beginning with the general plan outlined by the National Heart and Lung Institute in the initial solicitation of contract proposals. The protocol is designed to test the hypothesis that lowering serum cholesterol by diet, reducing high blood pressure by diet and drugs, and cessation of cigarette smoking will result in a reduced risk of (a) death from coronary heart disease (CHD), (b) combined fatal CHD and nonfatal myocardial infarction, (c) deaths from all cardiovascular disease, and (d) death from all causes, over a period of 6 years among men aged 35–57 without initial evidence of CHD. After screening 361,662 men, from 1974 to early 1976, 12,866 from the upper end of the risk spectrum of CHD on the basis of serum cholesterol, blood pressure, and smoking habits, were randomly assigned either to a program of Special Intervention (SI) directed toward altering these risk factors or to their usual source of medical care (UC). Men in the UC group have been evaluated once each year in the clinic without direct intervention on the risk factors. Men in the SI group participated in an initial intensive series of group sessions designed to assist in modification of behavior relating to the three risk factors. The SI men have since been invited to the clinic at least three times each year to maintain and increase risk factor change. Changes in the intervention protocol have resulted mainly from difficulty in achieving the expected response in serum cholesterol. These changes have included greater emphasis on control of body weight, the recommendation of more rigorous dietary specifications for those with persistently elevated levels of serum cholesterol, and advice to increase physical activity.     

The multiple risk factor intervention trial (MRFIT): IV. Intervention on blood lipids

The results are presented for the first 4 years of the Multiple Risk Factor Intervention Trial (MRFIT) nutrition intervention program. Study participants were at high risk (upper 10–15%) for Coronary Heart Disease (CHD). The Special Intervention (SI) group reached and sustained the goals of an eating pattern originally designed to limit cholesterol intake to less than 300 mg/day, with less than 10% of calories as saturated fat and not more than 10% as polyunsaturated fat. By the end of the first year, mean serum total cholesterol had fallen by 6.3% from the mean initial value of 254 mg/dl. The magnitude of the decrease became slightly greater in the ensuing years, reaching 7.4% by the fourth annual visit. Substantially larger decreases in mean serum cholesterol level were observed in the subgroups with the highest baseline level, greatest weight loss, in those who did not smoke, and in those who had normal blood pressure on entry. The changes in cholesterol level were accompanied by parallel changes in mean plasma LDL cholesterol, which also fell by 6.6% over the 4 years, but mean HDL cholesterol was not substantially altered. Comparison with earlier population data suggests that the overall responses to the MRFIT eating pattern were limited by the apparent fact that participants had already made self-initiated changes toward the fatcontrolled dietary pattern before they entered the study.     

The multiple risk factor intervention trial in the U.S. a summary of results at four years in special intervention and usual care men

Four-year results of the Multiple Risk Factor Intervention Trial indicate that an integrated approach to lifestyle modification of multiple risk factors is feasible and achieves significant lowering of risk factors compared with a group referred to usual medical care. The greatest changes and differences were in cigarette smoking. The hypertension treatment result met design predictions in the Special Intervention (SI) group. However, at 4 years the difference between groups was less than predicted, primarily due to unanticipated effectiveness of treatment of elevated pressures in the Usual Care (UC) group, reflecting recent secular changes in hypertension detection and control in the U.S. Similarly, the serum cholesterol net fall in the SI compared to UC group was 59% of goal, in part because of an unanticipated reduction in the UC group. The risk factor differences between groups were considerable, even though in some areas short of initial design expectations. The most serious consequence of a less than anticipated difference in risk characteristics between groups is an effective loss of power to detect significant differences in major disease endpoints. A further major benefit from the study has been the demonstration of the ability to have diverse scientific disciplines work effectively together in the long-term preventive management of healthy but high-risk men.     

Predictors of outcome in a risk factor intervention trial using behavior modification

To evaluate factors related to successful completion of a behavior modification program aimed primarily at eating habits, 100 volunteers, 82 women and 18 men, 40 ± 1 ($\text{x ±}\text{SEM}$) years in age took part in a 20-week program in groups of 12–14 subjects. In the 65 subjects who completed the program, significant (P < 0.05) decreases in weight, skinfold thickness, systolic and diastolic blood pressure, total serum cholesterol, and uric acid were observed. Changes in HDL cholesterol and triglycerides were not significant. In both univariate and multivariate analysis, attrition was significantly associated with factors identified at entry—cigarette smoking, higher body weight, larger desired weight loss, and psychiatric history. Actual weight loss in subjects who completed the program was significantly greater in those with a modest weight loss goal, and in married subjects perceiving their spouse as supportive or overweight. Decreases in total serum cholesterol were significantly smaller in subjects with a family history of cardiovascular disease. Thus factors that predict the outcome of a behavior modification intervention program for cardiovascular risk factor reduction can be identified at entry. Other strategies should be developed for poor responders; this strategy may be encouraged for use in potentially good responders.     

Randomized controlled trial of a web-based primary care intervention for multiple health risk behaviors

BACKGROUND: Physical inactivity, low fruit and vegetable intake, hazardous drinking, and smoking are leading risk factors for disease and injury. The aim of this study was to obtain estimates of efficacy in reducing the first three of these behaviors. METHOD: The design was a randomized controlled trial: 218 patients (17-24 years) attending a student health service at a New Zealand university in 2003 were assigned to: (A) web-based assessment and personalized feedback (n = 72); or (B) assessment only (n = 74); or (C) minimal contact (n = 72). Outcome measures were the proportion meeting recommendations for fruit and vegetable consumption, physical activity, and alcohol consumption 6 weeks later. RESULTS: Follow-up assessments were attained for 86% of participants, with no evidence of differential attrition. There were significant differences in the proportion meeting recommendations for fruit and vegetable consumption and physical activity in group A relative to C. Hazardous drinking prevalence did not vary significantly by group. CONCLUSIONS: Differences appear attributable to the intervention. The intervention could be routinely provided in primary care, and its efficacy could be assessed in a large randomized controlled trial.     

Multiple risk factor intervention trial (MRFIT).: VI. Intervention on blood pressure

The MRFIT blood pressure data derived from the Special Intervention (SI) group of men over the first 4 years are presented, and the results of the hypertension treatment program are reviewed. A therapeutic goal diastolic blood pressure (DBP) was established for each man determined to be hypertensive which included men with DBP ?90 mm Hg and men who were already taking antihypertensive drugs. A stepped care protocol was used to guide the drug treatment. At the fourth annual examination, 63.8% of the 5,790 SI men seen had been previously declared hypertensive. The mean baseline blood pressure (BP) for the hypertensive group was 140.3 mm Hg, systolic, and 94.5 mm Hg, diastolic, and at the 48-month visit, the mean BP was 120.7 mm Hg, systolic, and 82.5 mm Hg, diastolic. Of the hypertensive men seen at 48 months, 87.3% were taking antihypertensive drugs, 65.4% were at or below their goal pressure, and 83.5% had a DBP <90 mm Hg. Most men on antihypertensive drug therapy were at protocol Step 1 or Step 2, receiving a diuretic agent alone (32.9%), or in combination with an antiadrenergic drug (40.4%). Data for specific drug regimens are presented. Older men and men with higher BP levels at entry had a better response. The MRFIT BP results, achieved within a context of a multiple-risk-factor intervention program, compare favorably with the results from recently reported trials that focused solely on the treatment of mild hypertension.     

脑动脉瘤介入治疗策略及危险因素研究

目的探讨脑动脉瘤介入治疗的策略及危险因素。方法将46例行开颅夹闭术患者设置为对照组,将29例行脑动脉瘤介入术的患者设置为研究组,比较分析两组患者的疗效;对脑动脉瘤介入术的危险因素进行Logistic分析。结果研究组患者的疗效与对照组相比差异显著,P﹤0.05;单因素分析显示,动脉粥样硬化、糖尿病、动脉瘤大小、血管痉挛为动脉瘤破裂的影响因素,吸烟史、动脉瘤大小、血管痉挛、瘤颈特征为血栓形成的影响因素P值均﹤0.05;多因素Logistic回归分析显示动脉粥样硬化和血管痉挛为动脉瘤破裂的独立危险因素,瘤颈特征为血栓形成的唯一独立危险因素,P﹤0.05。结论脑动脉瘤介入术的疗效优于开颅夹闭术;动脉粥样硬化、血管痉挛和瘤颈特征是影响动脉瘤介入术并发症的主要危险因素。     

Composite cardiovascular risk outcomes of a work-site intervention trial.

OBJECTIVES: Two composite outcome measures were used to assess the efficacy of work-site risk factor interventions: the Framingham multiple logistic function and a standardized composite equation that was an unweighted combination of risk factors. METHODS: Twenty-eight work sites in Sydney, Australia, were randomly assigned to health risk assessment, risk factor education, behavioral counseling, or behavioral counseling plus incentives. RESULTS: Over 12 months, scores on the multiple logistic function increased for the behavioral counseling plus incentives condition relative to the other conditions. Standardized scores decreased for behavioral counseling relative to the incentive condition and the average of all other conditions. CONCLUSIONS: Behavioral counseling produces larger changes in the life-style behaviors contributing to coronary heart disease risk than other commonly used interventions.     

Social desirability trait influences on self-reported dietary measures among diverse participants in a multicenter multiple risk factor trial

Data collected at 4 Behavioral Change Consortium sites were used to assess social desirability bias in self-reports derived from a dietary fat screener (PFat), a dietary fruit and vegetable screener (FVS), and a 1-item question on fruit and vegetable intake. Comparisons were made with mean intakes derived from up to 3 24-h recall interviews at baseline and follow-up (at 12 mo in 3 sites, 6 mo in the fourth). A social-desirability-related underestimate in fat intake on the PFat relative to the 24HR (percentage energy as fat) was evident in women [baseline b = -0.56 (P = 0.005); follow-up b = -0.62 (P < 0.001)]. There was an overestimate in FVS-derived fruit and vegetable consumption (servings/week) in men enrolled in any intervention at follow-up (b = 0.39, P = 0.05) vs. baseline (b = 0.04, P = 0.75). The 1-item fruit and vegetable question was associated with an overestimate at baseline in men according to SD score (b = 0.14, P = 0.02), especially men with less than college education (b = 0.23, P = 0.01). Women with less than college education expressed a similar bias at follow-up (b = 0.13, P = 0.02). Differences in the magnitude of bias according to gender, type of instrument used, and randomization condition are comparable to what has been seen for other instruments and have important implications for both measuring change in studies of diet and health outcomes and for developing methods to control for such biases.     

Methods of quantifying change in multiple risk factor interventions

OBJECTIVE: Risky behaviors such as smoking, alcohol abuse, physical inactivity, and poor diet are detrimental to health, costly, and often co-occur. Greater efforts are being targeted at changing multiple risk behaviors to more comprehensively address the health needs of individuals and populations. With increased interest in multiple risk factor interventions, the field will need ways to conceptualize the issue of overall behavior change. METHOD: Analyzing data from over 8000 participants in four multibehavioral interventions, we present five different methods for quantifying and reporting changes in multiple risk behaviors. RESULTS: The methods are: (a) the traditional approach of reporting changes in individual risk behaviors; (b) creating a combined statistical index of overall behavior change, standardizing scores across behaviors on different metrics; (c) using a behavioral index; (d) calculating an overall impact factor; and (e) using overarching outcome measures such as quality of life, related biometrics, or cost outcomes. We discuss the methods' interpretations, strengths, and limitations. CONCLUSION: Given the lack of consensus in the field on how to examine change in multiple risk behaviors, we recommend researchers employ and compare multiple methods in their publications. A dialogue is needed to work toward developing a consensus for optimal ways of conceptualizing and reporting changes in multibehavioral interventions.     

The impact of behavioural screening on intervention outcomes in a randomised,controlled multiple behaviour intervention trial

Background  

With an increasing research focus on multiple health behaviour change interventions, a methodological issue requiring further investigation is whether or not to employ pre-trial behavioural screening to exclude participants who are achieving a pre-specified level of one or more behaviours. Behavioural screening can be used to direct limited resources to participants most in need of a behaviour change intervention; but may reduce the representativeness of the sample and limit comparability with trials that do not employ pre-trial behavioural screening. Furthermore, the impact of this type of screening on intervention participation and intervention effects is unknown.     

多(双)胎脑瘫儿童高危因素及预后分析

目的:探讨多(双)胎脑瘫儿童高危因素与脑瘫发生率之间的关系,以及早期综合康复治疗对患儿预后的影响。方法:采用回顾性调查分析的方法,对32个家庭60例多(双)胎儿童产前母体因素、产时及新生儿危险因素进行调查分析,同时应用Gesell发育量表进行测查,并对结果进行综合分析。结果:60例多(双)胎儿童脑瘫发生率为81.6%,其中有1种、2种、3种及4种以上高危因素的脑瘫发生率分别为73.3%、80.0%、85.7%、100.0%(t=12.976,P=0.011)。脑瘫高危因素依次为低出生体重(88.3%)、早产(73.3%)、窒息(21.6%)、先兆流产(21.6%)、高胆红素血症(15.0%)、缺氧缺血性脑病(13.3%)、蛛网膜下腔出血(8.3%)、早破水(13.3%)、孕早期感染(11.6%)、低血糖(10.0%)、妊高征(10.0%)、宫内窘迫(3.3%)、器械助娩(3.3%)。所有脑瘫患儿均给予综合康复治疗,其中6月以内进行综合康复治疗的患儿总有效率为100.0%,1岁以后开始综合康复治疗的总有效率仅为45.0%(t=21.103,P=0.000)。结论:多(双)胎儿易发生早产及低出生体重等高危因素,且所合并的高危因素越多其脑瘫发生率越高(P<0.05)。早期发现和早期康复治疗可显著降低脑瘫发生率。