Plan and operation of the NHANES I Epidemiologic Followup Study, 1992

OBJECTIVES: The NHANES I Epidemiologic Followup Study (NHEFS) is a longitudinal study that uses as its baseline those adult persons 25-74 years of age who were examined in the first National Health and Nutrition Examination Survey (NHANES I). NHEFS was designed to investigate the association between factors measured at baseline and the development of specific health conditions. The three major objectives of NHEFS are to study morbidity and mortality associated with suspected risk factors, changes over time in participants' characteristics, and the natural history of chronic disease and functional impairments. METHODS: Tracing and data collection in the 1992 Followup were undertaken for the 11,195 subjects who were not known to be deceased in the previous surveys. No additional information was collected in the 1992 NHEFS for the 3,212 subjects who were known to be deceased before the 1992 NHEFS data collection period. RESULTS: By the end of the 1992 NHEFS survey period, 90.0 percent of the 11,195 subjects in the 1992 Followup cohort had been successfully traced. Interviews were conducted for 9,281 subjects. An interview was conducted for 8,151 of the 8,687 surviving subjects; 551 interviews were administered to a proxy respondent because the subject was incapacitated. A proxy interview was conducted for 1,130 of the 1,392 decedents identified in the 1992 NHEFS. In addition, 10,535 facility stay records were collected for 4,162 subjects reporting overnight facility stays. Death certificates were obtained for 1,374 of the 1,392 subjects who were identified as deceased since last contact. Approximately 32 percent of the NHEFS cohort is known to be deceased with a death certificate available for 98 percent of the 4,604 NHEFS decedents.     

Effectiveness of interventions to improve patient compliance: a meta-analysis

OBJECTIVES: This article summarizes the results of 153 studies published between 1977 and 1994 that evaluated the effectiveness of interventions to improve patient compliance with medical regimens. METHODS: The compliance interventions were classified by theoretical focus into educational, behavioral, and affective categories within which specific intervention strategies were further distinguished. The compliance indicators broadly represent five classes of compliance-related assessments: (1) health outcomes (eg, blood pressure and hospitalization), (2) direct indicators (eg, urine and blood tracers and weight change), (3) indirect indicators (eg, pill count and refill records), (4) subjective report (eg, patients' or others' reports), and (5) utilization (appointment making and keeping and use of preventive services). An effect size (ES) r, defined as Fisher's Z transformation of the Pearson correlation coefficient, representing the association between each intervention (intervention versus control) and compliance measure was calculated. Both an unweighted and weighted r were calculated because of large sample size variation, and a combined probability across studies was calculated. RESULTS: The interventions produced significant effects for all the compliance indicators (combined Z values more than 5 and less than 32), with the magnitude of effects ranging from small to large. The largest effects (unweighted) were evident for refill records and pill counts and in blood/urine and weight change studies. Although smaller in magnitude, compliance effects were evident for improved health outcomes and utilization. Chronic disease patients, including those with diabetes and hypertension, as well as cancer patients and those with mental health problems especially benefited from interventions. CONCLUSIONS: No single strategy or programmatic focus showed any clear advantage compared with another. Comprehensive interventions combining cognitive, behavioral, and affective components were more effective than single-focus interventions.     

Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study

BACKGROUND: There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses. METHODS AND RESULTS: The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (chi2 P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women. CONCLUSIONS: In our large, population-based sample, there is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women. Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted.     

The optimal blood pressure reduction

OPTIMAL BLOOD PRESSURE REDUCTION: The optimal blood pressure reduction when treating arterial hypertension is obviously the one which causes the maximum achievable prevention of hypertension-associated cardiovascular morbidity and mortality. This goal has not yet been reached by present approaches to antihypertensive treatment. Several large intervention trials in hypertension have shown that treated hypertensive patients still have an increased risk of cardiovascular morbidity and mortality in spite of receiving antihypertensive treatment. One possible explanation for this is that treated blood pressure is rarely, if ever, reduced to strictly normotensive levels. Another explanation, favored by proponents of the J-curve argument, is that excessive lowering of blood pressure may increase cardiovascular risks. DATA AVAILABLE FROM INTERVENTION TRIALS: So far, two prospective intervention trials have addressed this problem, the Swedish BBB (Treat Blood Pressure Better) study, for which results have been published, and the much larger Hypertension Optimal Treatment (HOT) study, which is still under way. Moreover, new epidemiological data from the Framingham Heart Study and the study of 50-year-old men in Gothenburg suggest that active intervention against arterial hypertension may change the pattern of blood pressure distribution in the population towards lower levels, also in untreated subjects, suggesting an additional and unexpected benefit from antihypertensive treatment.     

Diurnal variation in plasma ethanol levels of TO and CBA mice on chronic ethanol drinking or ethanol liquid diet schedules

Data accumulated from epidemiological observations, intervention trials and studies on experimental animals provide a growing body of evidence of the influence of various dietary components on blood pressure. Dietary sodium, usually taken in the form of sodium chloride (common salt), is positively associated with blood pressure, and in many hypertensive patients reduction in sodium intake lowers blood pressure. On the other hand, in certain patients potassium, calcium and magnesium may be protective electrolytes against hypertension. Dietary fats, especially n-3 polyunsaturated fatty acids, may also influence blood pressure, whereas the possible role of other macronutrients, such as proteins and carbohydrates, or vitamins in the regulation of blood pressure is less well understood. Occasional ingestion of coffee transiently increases blood pressure, but the effects of habitual coffee consumption are controversial. Excessive use of alcohol on a regular basis has been associated with elevated blood pressure. It has also been shown in case reports that large amounts of liquorice lead to the development of hypertension. Thus, with appropriate dietary modifications, it is possible to prevent the development of high blood pressure and to treat hypertensive patients with fewer drugs and with lower doses. In some patients antihypertensive medication may not be at all necessary.     

Hypertension, coronary artery and cerebrovascular diseases in the population. Has epidemiology changed in the last decades?

Life expectancy has significantly increased in the last decades in many western populations, due to the fall of total and cardiovascular death rate. However, morbidity from cardiovascular diseases has decreased to a smaller extent. The overall population risk profile has improved, but it is still unsatisfactory. This is true for blood pressure control (with only 20% of hypertensive patients achieving normotension with antihypertensive drugs), hypercholesterolemia (with borderline-high serum cholesterol levels in 50% of the population), and smoking habits. Other potential causes of the poor cardiovascular prevention are: 1) a limited knowledge of the optimal blood pressure goal with antihypertensive treatment, 2) scanty information on the long term effects of antihypertensive drugs on cerebral and coronary circulation. Finally, little is being done to improve primary prevention in youth, when the slowly progressing atherosclerotic plaque formation is already on the way. To improve the cost / effectiveness of cardiovascular prevention, efforts must concentrate on the early identification of the subjects at the highest risk and on health promotion among youngsters. Large epidemiological trials conducted from the early 50s have provided convincing evidence of the multifactorial origin of cardiovascular diseases and encouraged the implementation of population based primary and secondary preventive measures, including antihypertensive treatment, as well as dietary and life-style modifications. It is now time to start asking ourselves whether or not we are satisfied with the results obtained in terms of reduced morbidity and mortality, whether these results are the direct consequence of these measures and whether or not we can do even better. The present work reviews some of the most recent comparative reports on the epidemiology of cardiovascular diseases in different populations, and some intervention trials to answer these questions and to help in identifying the most cost-effective approach to cardiovascular disease prevention in the next few years.     

Type II diabetic nephropathy: its clinical course and therapeutic implications

Type II diabetes is responsible for more end-stage renal disease in the United States than any other single condition. Until recently, the majority of research in diabetic nephropathy has focused on patients with type I diabetes despite the fact that type II nephropathy is a more prevalent condition. The notion that there are major differences between the nephropathy of these two types of diabetes is not supported by recent literature. The biggest difference appears to be related to ethnic risk. Histopathologic differences are now being described as well. Clinical interventional trials are few compared to type I diabetes; however, it seems that maneuvers that improve renal prognosis in patients with type I diabetes (blood pressure control, blood glucose control, and the use of angiotensin-converting enzyme inhibitors) apply to the type II population as well. Some of the calcium channel blockers lower proteinuria to a degree that suggests renoprotection and may further improve outcome.     

Deficient health knowledge, diet, and other lifestyles in smokers: is a multifactorial approach required?

BACKGROUND: Data from the Scottish Heart Health Study, a random cross-sectional sample of middle-aged men and women, are used to compare health knowledge, behavior, and lifestyles between 4896 smokers and 4595 nonsmokers. METHODS: Smokers are identified from self-reports with biochemical validation. They are compared with nonsmokers using analysis of covariance and logistic regression, adjusting for age and social class. RESULTS: Smokers are found to have poorer dietary knowledge than nonsmokers, although both groups are well-informed on some aspects of diet. Knowledge of personal risk modifiers for coronary heart disease and recent intention to improve lifestyle are both worse among smokers. Smokers have lower intakes of the antioxidant vitamins and fiber, but higher intakes of dietary cholesterol and alcohol than nonsmokers. They also tend to have higher salt intake and eat a greater proportion of saturated fat, butter, or hard margarine, and full-fat milk. High-density lipoprotein cholesterol levels are lower, but triglycerides, fibrinogen, and, for women only, total serum cholesterol levels are higher among smokers. On the other hand, body mass index and diastolic blood pressure are lower among smokers. CONCLUSIONS: In addition to advice to give up smoking, smokers should be counseled to improve their diet. The positive message to eat more fresh fruit and vegetables would be particularly helpful.     

Menopause and hormone replacement therapy

Menopause is a normal part of life of most women and can be made easier with appropriate information about the events that occur. For those women who desire help for bothersome menopausal symptoms, effective therapy can be offered. The use of HRT for prevention is more complex. Several large randomized clinical trials, including the Women's Health Initiative (WHI) and the Heart and Estrogen Replacement Therapy Study (HERS) in the United States, are currently underway. These trials, which have as end points clinical events such as myocardial infarction, sudden death, fractures, and cancer, will provide answers to many of the questions raised in this discussion. Until the results of these trials are available, clinicians must be prudent in their recommendations and should keep their patients apprised of the relevant uncertainties of preventive HRT.     

High blood pressure and end-organ damage

BACKGROUND: Findings from numerous epidemiologic and clinical studies worldwide attest to a strong, graded, consistent relationship between blood pressure level and cardiovascular-renal diseases, subclinical and clinical, nonfatal and fatal. OBJECTIVE: This review summarizes results from selected prospective observational studies, primarily from US populations, and from randomized clinical trials. Review Analyses from the Multiple Risk Factor Intervention Trial (MRFIT) subjects (middle-aged men) and the Framingham Heart Study (middle-aged and elderly men and women) clearly establish that systolic blood pressure is a more powerful predictor of cardiovascular events than diastolic pressure. Wherever the full range of blood pressure has been examined, for example for systolic pressure in the MRFIT subjects and for diastolic pressure in pooled data from nine epidemiologic studies, the associations for coronary heart disease and stroke are seen to extend over the whole range, including 'normotensive' levels. In MRFIT, this continuous relationship has also recently been shown for end-stage renal disease and both systolic and diastolic pressure. Data from Framingham document further associations with peripheral vascular disease, congestive heart failure, and both electrocardiographic and echocardiographic left ventricular hypertrophy. Several studies are row available demonstrating a relationship between hypertension and carotid wall intimal-medial thickness. Finally, the causal nature of the relationships with major cardiovascular events is supported by the results of 17 large-scale randomized trials of blood-pressure-lowering using primarily diuretic- and beta-blocker-based drug regimens. CONCLUSIONS: These trials have demonstrated highly significant reductions in fatal and nonfatal stroke and major coronary heart disease. There are few trial data, however, on health benefits from further reducing blood pressure among normotensive persons.     

Hypertension and endstage renal disease

OBJECTIVE: To review current literature regarding the development of hypertensive renal disease, its epidemiology, and its pathophysiology. This review focuses on strategies to slow or halt the progression of endstage renal disease (ESRD) in hypertension, including the role of blood pressure control, different types of antihypertensive agents, early treatment, and dietary considerations. DATA SOURCES: Information was retrieved from searching the MEDLINE database for articles consisting of epidemiologic studies, clinical studies, and review articles pertaining to hypertension and ESRD. Information also was obtained from the US Renal Data System annual data reports. STUDY SELECTION: Emphasis was placed on clinical trials in the English language addressing issues in hypertension and ESRD. Clinical trials reporting relationships between blood pressure control and ESRD, as well as those comparing different antihypertensive agents, were evaluated. DATA EXTRACTION: The methodology and results from clinical trials were evaluated. Studies were assessed according to the measures of renal function used, baseline data collected, degree of blood pressure control, and antihypertensive therapy. DATA SYNTHESIS: Clinical trials including patients with essential hypertension, diabetes mellitus, and renal insufficiency of various etiologies were evaluated. The recommendations from these evaluations were based on study design and the types of populations used (i.e., blacks vs. whites, diabetics vs. nondiabetics). CONCLUSIONS: Blood pressure control is currently the most important strategy to slow or halt the progression of renal insufficiency in hypertensive individuals. Whether specific antihypertensives are renal protective is still controversial, but results from clinical trials are promising.     

Therapeutic approach in arterial hypertension with renal artery stenosis

Screening for renal artery stenoses in hypertensive patients aims at detecting lesions whose treatment (renal revascularization) will normalize or reduce blood pressure and correct or prevent reduced glomerular filtration. Consequently, screening tests such as renal artery duplex Doppler scanning, renal scintigraphy or digital-subtraction angiography are used in patients in whom hypertension is severe, drug-resistant or associated with renal failure. Surgical repair or transluminal angioplasty is not warranted for all stenoses, however, particularly in atheromatous stenoses where these procedures have a 1% mortality, a 10% morbidity and a 30% failure rate to improve blood pressure despite adequate anatomical outcome. Predictors of favourable blood pressure outcome following revascularization are aetiological (fibrous dysplasia rather than atheroma), historical (young age, short duration of hypertension), physiological (renal ischaemia confirmed by scintigraphy, lateralizing renal vein renin ratio) and anatomical (truncal rather than ostial or branch stenoses). Outcome of surgery and transluminal angioplasty has only been documented in retrospective, uncontrolled reports in which blood pressure improvement is overestimated via the placebo effect, habituation to blood pressure readings and optimization of drug treatment, the latter being frequently required despite adequate revascularization. The first prospective randomized trials evaluating angioplasty in atheromatous stenoses are underway and should provide objective information concerning the risk/benefit ratio of this procedure.     

Pathophysiological roles of human chymase

Angiotensin (Ang) II plays an important role in cardiovascular homeostasis such as regulation of blood pressure and tissue remodeling. Alternative Ang II-forming pathways, independent of Ang I converting enzyme (ACE), have been reported. Several serine proteinases including kallikrein, cathepsin G and chymase appear to be involved in ACE-independent Ang II formation in vivo. Among them, biochemical analysis revealed that chymase is a highly efficient Ang II-forming enzyme with a high substrate specificity against Ang I and is rich in various human tissues. However, the pathophysiological roles of chymase have not yet been clarified. Recent reports from us and others indicated that chymase seems to be related to development of atherosclerosis, cardiomyopathy, remodeling of cardiovascular tissues, rheumatoid arthritis and etc. In this review article, the recent findings for chymase related to cardiovascular diseases are summarized.     

Salt and hypertension at the close of the millenium

"Can that which is unsavory be eaten without salt?" This question was directed at none other than God by Job, who also had other important problems to ponder. The question posed in this review is the notion that essential hypertension is induced and/or sustained by an unnecessarily high salt intake. If this is indeed the case, then a reduction of salt intake might prevent or effectively treat essential hypertension. A cross-sectional epidemiological study of salt intake in populations showed a positive association of sodium excretion with median blood pressure and the prevalence of hypertension; however, when four disparate populations were deleted, the associations disappeared. A Scottish report on a similarly large population minimized the importance of dietary sodium. A recently analysis of the National Health and Nutrition Examination Survey (NHANES) data base does not support the idea that lower salt intake improves all-cause or cardiovascular mortality; however, the analysis is not without weaknesses. Salt-sensitivity is based on the idea that some persons might be more susceptible to salt-induced effects on blood pressure than others. Indeed, several monogenic syndromes exhibit marked salt-sensitivity and their clarification has facilitated our understanding of basic mechanisms. Allelic variants of several genes may be important in salt-sensitive patients with essential hypertension. Meta-analyses of intervention trials in patients with essential hypertension show about a 5 mm Hg decrease in blood pressure with salt restriction. Among the normotensive, this decrease is less than 2 mm Hg. In terms of efficacy, salt restriction has not been shown superior to weight loss or a "vegetable" diet. Nonpharmacological approaches in hypertensive patients should be based on a comprehensive approach.     

Ambulatory blood pressure monitoring is a useful clinical tool in nephrology

Hypertension is a key factor in the genesis and deterioration of many renal diseases and is also a risk factor for death in patients with end-stage renal disease. However, the standard methods of measurement are prone to variability, especially in patients undergoing dialysis. The technique of ambulatory blood pressure monitoring allows a better assessment of overall blood pressure levels and promises to assume a bigger role in the care of renal patients. Ambulatory blood pressure monitoring is widely used in hypertension trials, and the reports of several consensus meetings on the clinical uses of ambulatory blood pressure monitoring have been published. Two similar validation protocols now exist for ambulatory blood pressure monitors, and tables of population-based normal blood pressures for age and gender are available. The available evidence suggests that ambulatory blood pressure compared with blood pressure measured in the physician's office is better correlated to left ventricular mass in subjects with chronic renal disease. Furthermore, studies in subjects with chronic renal disease and those undergoing renal replacement therapy show that blood pressure control is suboptimal in many patients and that nocturnal blood pressure is generally higher than in control subjects. Further insights into overall blood pressure behavior in this population will certainly emerge in the future.     

Knowledge of the utilization of preventive practices through a telephone survey

OBJECTIVES: To determine knowledge and use of preventive practices (cervical cytology, mammography and taking blood pressure) through a telephone survey. DESIGN: Crossover study. SETTING: Billabona Health Centre (Guipúzcoa). PARTICIPANTS: People over 15 in the Health Centre's catchment area. MAIN RESULTS: The sample size was 800 people. It reached 80% telephone coverage with a reply rate of 86.09% (278 men and 273 women). 76.5% of women stated they had heard of cervical cytology; and 80.2% mammography. 87.5% had had their blood pressure taken on some occasion. CONCLUSIONS: Both cervical cytology and mammography are well-known preventive procedures, although they could always be improved, whereas taking blood pressure is a widespread practice in all age-groups.     

Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension

OBJECTIVES: The primary objective of the International Verapamil SR/Trandolapril Study (INVEST) is to compare the risk for adverse outcomes (all-cause mortality, nonfatal myocardial infarction [MI] or nonfatal stroke) in hypertensive patients with coronary artery disease (CAD) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy. BACKGROUND: Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent, for which reductions in morbidity and mortality are documented from randomized trials but are less than expected from epidemiologic data. For this reason, recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors. While these agents reduce blood pressure, outcome data from large randomized trials are lacking, but some case-control data, dominated by short-acting dihydropyridines, suggest an increased risk of cardiovascular events. These studies had methodologic limitations and did not differentiate among calcium antagonist types and formulations. Several studies differentiating among calcium antagonist types and an overview of published randomized trials show no increased risk with verapamil and suggestion for benefit in CAD patients. METHODS: A total of 27,000 CAD patients with hypertension will be randomized at 1,500 primary care sites to receive either a calcium antagonist-based (verapamil) or beta-blocker/diuretic-based (atenolol/hydrochlorothiazide) antihypertensive care strategy. The study uses a novel, electronic "paper-less" system for direct on-screen data entry, randomization and drug distribution from a mail pharmacy linked to the coordination center via the Internet. RESULTS: Contract negotiations with the United States and international sites are ongoing. Patients being enrolled are predominantly elderly (72% aged 60 years or older) men (54%), with either an abnormal coronary angiogram or prior MI (71%). In addition to hypertension, CAD and elderly age, most patients (89%) have one or more associated conditions (diabetes, dyslipidemia, smoking, cerebral or peripheral vascular disease, etc.) contributing to increased risk for adverse outcome. While 26% have diabetes, most of these are noninsulin dependent. Using the protocol strategies, target blood pressures (according to JNC VI) have been reached in 58% at the fourth visit, and as expected most (89%) are requiring multiple antihypertensive drugs. CONCLUSION: The design and baseline characteristics of the initial patients recruited for a prospective, randomized, international, multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described.     

Development of a perioperative nursing diagnoses flow sheet

Traditionally, health care professionals in the preoperative, intraoperative, and postoperative phases of care have used perioperative records that focus on the technical aspects of the care provided (eg, blood pressure, pulse measurements; equipment used) and leave room for only short narratives to document nursing care. Such formats often do not document the multitude of activities or interventions perioperative nurses provide. The question raised at the DePaul Health Center, St Louis, was: "Where do we document our nursing diagnoses and plan of care?" The response was to create a nursing diagnosis task force that investigated the feasibility of a form professional nurses could use in all phases of patient care. This investigation led to the development, implementation, and universal use of a perioperative nursing diagnoses flow sheet within the surgical services department.     

Quantitation of change in the medullary compartment in renal allograft by ultrasound

PURPOSE: This study was completed to determine the current knowledge and documentation patterns of nursing staff in the prevention of pressure ulcers and to identify the prevalence of pressure ulcers. METHODS: This pre-post intervention study was carried out in three phases. In phase 1, 67 nursing staff members completed a modified version of Bostrom's Patient Skin Integrity Survey. A Braden Scale score, the presence of actual skin breakdown, and the presence of nursing documentation were collected for each patient (n = 43). Phase II consisted of a 20-minute educational session to all staff. In phase III, 51 nursing staff completed a second questionnaire similar to that completed in phase I. Patient data (n = 49) were again collected using the same procedure as phase I. RESULTS: Twenty-seven staff members completed questionnaires in both phase I and phase III of the study. No statistically significant differences were found in the knowledge of the staff before or after the educational session. The number of patients with a documented plan of care showed a statistically significant difference from phase I to phase III. The number of patients with pressure ulcers or at risk for pressure ulcer development (determined by a Braden Scale score of 16 or less) did not differ statistically from phase I to phase III. CONCLUSION: Knowledge about pressure ulcers in this sample of staff nurses was for the most part current and consistent with the recommendations in the Agency for Health Care Policy and Research guideline. Documentation of pressure ulcer prevention and treatment improved after the educational session. Although a significant change was noted in documentation, it is unclear whether it reflected an actual change in practice.     

Microalbuminuria is not rare before 5 years of IDDM. EURODIAB IDDM Complications Study Group and the WHO Multinational Study of Vascular Disease in Diabetes Study Group

Microalbuminuria is thought to be rare in people with insulin-dependent diabetes mellitus (IDDM) for less than 5 years. We measured its prevalence in 733 clinic-attending IDDM patients with diabetes duration of 1-5 years in two large multicenter studies [EURODIAB IDDM Complications Study and the World Health Organization (WHO) Multinational Study]. We also compared characteristics of microalbuminuric patients with IDDM for 1-5 years versus more than 5 years' duration. Albumin excretion rate was measured from a timed 24-h urine collection in the EURODIAB Study. Proteinuria was measured by the salicylsulphonic acid test in the WHO Study. The prevalence of microalbuminuria (20-200 micrograms/min, EURODIAB) was 18% [95% confidence interval (CI) 13%-22%)]. The prevalence of light proteinuria was 15% (9%-20%, WHO study). Raised protein excretion was a consistent finding in 34 of the 36 centers. The increased cardiovascular risk (raised blood pressure and total cholesterol) associated with microalbuminuria in patients with IDDM for more than 5 years was also apparent in those with diabetes for 1-5 years. However, repeat urine testing suggested that microalbuminuria before 5 years was more likely to be transient or reversible. In conclusion, these two studies in 36 centers, which used different methods more than 10 years apart, show consistently that raised urinary albumin excretion occurs before 5 years of IDDM. The clinical significance of this needs to be examined by prospective observation.