Correlates and consequences of diffuse atherosclerosis in men with coronary heart disease. Veterans Affairs High-Density Lipoprotein Intervention Trial Study Group.

BACKGROUND: Peripheral atherosclerosis is a strong and independent predictor of mortality even in patients with known coronary heart disease. However, the prevalence, correlates, and potential adverse effects on quality of life associated with combined coronary heart disease and clinically evident cerebrovascular or lower-extremity atherosclerosis are not known. Identification of patients with "diffuse atherosclerosis" may enhance treatment of modifiable risk factors and alter therapeutic strategies. METHODS: We conducted a cross-sectional analysis of 2531 men younger than 73 years with coronary heart disease, low-density lipoprotein cholesterol levels of 3.62 mmol/L (140 mg/dL) or less, and high-density lipoprotein cholesterol level of 1.03 mmol/L (40 mg/dL) or less who were participating in Department of Veterans Affairs Cooperative Study 363 (the Veterans Affairs High-Density Lipo-protein Intervention Trial. Baseline demographic, medication, comorbidity, and atherosclerotic risk factor data were assessed by means of a standardized questionnaire. All plasma lipid levels were determined after a 12-hour fast by a central standardized lipid laboratory. Health status was determined by baseline reported symptoms, medical comorbidities, and the Psychological General Well-being Index. Clinically evident diffuse atherosclerosis was defined as a documented history of lower-extremity atherosclerosis or cerebrovascular disease. RESULTS: The mean age of all participants was 63.5 years. The mean plasma lipid values were as follows: total cholesterol, 4,52 mmol/L (174.6 mg/dL); high-density lipo-protein cholesterol, 0.81 mmol/L (31.5 mg/dL); low-density lipoprotein cholesterol, 2.88 mmol/L (111.2 mg/dL); and triglycerides, 1.81 mmol/L (160.6 mg/dL). Diffuse atherosclerosis was present in 525 (21%). Lower-extremity atherosclerosis was reported in 10%, while cerebrovascular disease was present in 13%. After controlling for other variables, the following factors were associated with the presence of diffuse atherosclerosis: increased age, being unmarried, being retired, having less than a high school education, increased alcohol use, hypertension, cigarette smoking, and diabetes. There was no association between lipid levels and the presence of diffuse atherosclerosis. After adjustment for age, race, and comorbidities, men with diffuse disease still had a reduced quality of life compared with men without diffuse atherosclerosis, as defined by having a greater number of clinical symptoms, lower psychological well-being scores, and more advanced or complicated coronary heart disease. CONCLUSIONS: Clinically evident diffuse atherosclerosis is common in men with coronary heart disease and low levels of high-density lipoprotein cholesterol. Because diffuse atherosclerosis is associated with a reduced quality of life and several modifiable risk factors, early detection and aggressive risk factor intervention appear justified.

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.

Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group.

The purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2%. This prevalence increased to 18.2% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology.

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)

Distribution of lipids in 8,500 men with coronary artery disease. Department of Veterans Affairs HDL Intervention Trial Study Group.

In the present study we measured fasting lipid profiles in over 8,500 community-living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p < 0.003). With use of cut points established by the National Cholesterol Education Program, 87% of subjects had high LDL cholesterol (> or = 100 mg/dl), 38% had low HDL cholesterol (< 35 mg/dl), and 33% had high triglycerides (> 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol.

Coronary heart disease mortality and sudden death among the 35-44-year age group in Allegheny County, Pennsylvania.

Deaths among 35- to 44-year-old black and white men and women residing in Allegheny County, Pennsylvania, were investigated. All coroner-certified nontraumatic deaths and practitioner-certified deaths coded as heart, cerbrovascular, or arterial disease, diabetes mellitus, and sudden or ill-defined causes were studied. Using autopsy, coroner, hospital, physician, and/or informant information about medical history, characteristics, and circumstances of death, physicians validated the deaths as due to coronary heart disease (CHD) or another cause. In 1984 to 1989, 616 deaths were investigated, 384 of which were sudden (within 24 hours of onset). Overall CHD mortality was 35.4/100,000/y for white males, 8.4/100,000/y for white females, 61.3/100,000/y for black males, and 19.5/100,000/y for black females. Although rates varied widely, characteristics, circumstances, and disease history were similar across race-sex groups. CHD mortality was 73% higher in black than white males. Approximately 80% of CHD deaths were sudden.

A historical perspective of elevated systolic vs diastolic blood pressure from an epidemiological and clinical trial viewpoint.

The decision to use diastolic blood pressure as the basis for therapeutic intervention for hypertension was based primarily on clinical trials experience. The majority of observational studies shows as great or greater risk for elevated systolic blood pressure readings. Even many of the clinical trials in which a posteriori analyses have been performed confirm a greater effect of systolic rather than diastolic blood pressure as a predictor of coronary heart disease mortality. The current practice of using diastolic blood pressure readings as the sole treatment criterion should be reexamined in light of the observational studies and clinical trials reviewed here.

Lower extremity arterial disease in elderly subjects with systolic hypertension.

The ratio of ankle-to-arm systolic blood pressure (ankle/arm index or AAI) appears to be a non-invasive indicator of flow-significant atherosclerosis and may be a useful measure of burden of disease in a high risk population. The prevalence of lower extremity arterial disease (LEAD) was assessed by this method in the Systolic Hypertension in the Elderly Program (SHEP). Subjects were aged 60 and older with systolic blood pressure greater than 160 mmHg upon entry to the study. An AAI of 0.90 or less was considered indicative of flow-significant LEAD. The prevalence of LEAD by this method was 26.7% (50/187), while the prevalence of intermittent claudication (IC) was only 6.4% (12/187). Of those with IC, 66.7% (8/12) had confirmed LEAD. The prevalence of LEAD as measured by AAI increased with age in women and was associated with a history of current smoking and lower levels of high density lipoproteins. In this study population with systolic hypertension, LEAD, as measured by the AAI, is more prevalent than previously described in elderly populations and is associated with other risk factors for atherosclerosis.

Assessing the use of medications in the elderly: methods and initial experience in the Cardiovascular Health Study. The Cardiovascular Health Study Collaborative Research Group.

The Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary heart disease and stroke, recruited 5201 community-dwelling adults aged 65 years or older. To assess the prevalence of medication use at baseline, we used the method of medication inventory and transcribed information about drug names and doses from prescription bottles. Using a specially-written computer program, persons without a knowledge of drug nomenclature coded 10,511 (89%) of the 11,846 medicines entered. We compared the results of the medication inventory and answers to questions on specific medications for reliability and validity. The use of beta-blockers and beta-agonists assessed by the method of medication inventory, but not by the method of directed recall, was associated with a significant effect on mean heart rate. Among 5197 participants with medication data, 76.1% were taking at least one medicine, and the mean number of drugs per person was 2.28. Among those with a reported history of high blood pressure, participants with cardiovascular disease (CVD) were more likely to be treated, and they were more likely to be taking beta-blockers and calcium-channel blockers than those without CVD. Daily aspirin use was also more common among those with CVD (30.5% of women and 43.2% of men) than among those without CVD (14.0% of women and 14.0% of men). The prevalence of post-menopausal estrogen use differed significantly among the four clinical centers (range = 5.5%-22.5% of women). We conclude that this method of assessing medications was easy to use and provided estimates of exposure to drugs that may affect risk of cardiovascular disease.

Advances in management of hypertension in older persons.

Recent studies have now demonstrated that it is more important to focus on the SBP level than the DBP level in older persons. In addition, recent studies indicate that persons over age 80 still derive substantial benefit from treating ISH or DH. Also, studies now show that low-dose diuretics have a more favorable impact on subsequent coronary heart disease rates than was previously demonstrated. Finally, although caution is urged, it is unlikely the J-shaped relationship between treated DBP or SBP and subsequent mortality is due to overly aggressive treatment of high blood pressure. Table 4 provides the authors' guidelines for treating older persons with high blood pressure.

Comparison of ambulatory and clinic blood pressure and heart rate in older persons with isolated systolic hypertension.

We compared the blood pressure (BP) measurements obtained with a random-zero sphygmomanometer and an ambulatory BP monitor in older persons with isolated systolic hypertension at one site of the multicenter, randomized, double-blind clinical trial, the Systolic Hypertension in the Elderly Program (SHEP) randomized clinical trial. The subjects were community-dwelling elderly participants with isolated systolic hypertension enrolled in the SHEP study and already receiving stable doses of double-blind medication (n = 35 for active treatment group; n = 32 for placebo group). We measured seated (clinic) BP obtained with a random-zero sphygmomamanometer, pulse rate, and BP and heart rate measurements obtained with an ambulatory BP monitor (average 24 h, daytime, and nighttime BP and heart rate). Across treatment groups clinic and ambulatory systolic BPs were not significantly different, but the placebo group had higher ambulatory, but not clinic, diastolic BPs. Within each treatment group (active treatment and placebo) there were no significant differences between clinic and average 24 h, daytime, or nighttime ambulatory systolic BPs. There were also no significant differences between clinic diastolic BP and average 24 h, daytime, or nighttime ambulatory diastolic BPs in the active treatment group, but in the placebo group average 24 h diastolic BP obtained by the ambulatory monitor was 4.6 mm Hg higher than clinic diastolic BP (P = .001). The average 24 h heart rate was 6 to 7 beats/min higher as measured by the ambulatory monitor compared to clinic pulse (P < .01). In the placebo group of this study, average 24 h ambulatory diastolic BPs were consistently higher than clinic diastolic BPs.(ABSTRACT TRUNCATED AT 250 WORDS)

The association of antihypertensive medication with serum creatinine changes in older adults.

Many of the potential effects of antihypertensive therapy, including renal function, have been inadequately investigated in clinical trials in older adults. In an observational study, we examined the association between treatment with various classes of antihypertensive agents and 3-year changes in serum creatinine in 1296 older adults with treated hypertension and without prior renal disease (mean age 72.2 years; 60% female; 30% diabetic; 42% with cardiovascular disease (CVD)) from the Cardiovascular Health Study. Baseline antihypertensive medications included thiazides (HCT), beta-adrenergic blockers, angiotensin converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), vasodilators (VAS), HCT + BB, HCT + ACE-I, HCT + CCB, HCT + VAS, loop diuretics (LOOP), and other combinations. Unadjusted results indicated that minimal changes in mean serum creatinine occurred over time for all therapies and only a few changes were statistically significant (HCT: +0.02 mg/dL, ACE-I: +0.04, CCB: +0.04; all P < .05; LOOP: +0.06 mg/dL; P < .001). In multivariate analyses with HCT users as the reference group and adjusting for baseline serum creatinine, age, sex, smoking, diabetes mellitus, CVD, height, weight, common carotid intima-media thickness, and use of allopurinol, phenytoin, cimetidine, and nonsteroidal antiinflammatory drugs, all of the relative changes were small and statistically nonsignificant except for HCT + VAS users (+0.07 mg/dL; P < .05). When users of the same therapy at baseline and follow-up were restricted, only LOOP users had significant albeit small changes in serum creatinine (+0.05 mg/dL; P < .05). Although results from clinical trials are needed to confirm these findings, these observational data suggest no major differences between specific antihypertensive therapies in 3-year serum creatinine changes in older adults without prior renal disease.

Does syndrome X exist in hypertensive elderly persons with impaired glycemic control?

BACKGROUND: This report focuses on the glycemic state in relation to insulin and lipid levels of a cohort of elderly hypertensive persons to estimate the prevalence of syndrome X. METHODS: A cross-sectional study was performed at the University of Tennessee, Memphis, and the General Clinical Research Center (GCRC) on 95 participants in the Trial of Nonpharmacologic Interventions in the Elderly (TONE) study who agreed to participate in an ancillary study. A standard oral glucose tolerance test (OGTT) with insulin and C-peptide levels and a fasting lipid profile were obtained. RESULTS: In this sample of healthy elderly participants with hypertension who were taking an antihypertensive medication, 43 (45.3%) had normal glucose tolerance (NGT), 41 (43.2%) had impaired glucose tolerance (IGT), and 11 (11.6%) had undiagnosed non-insulin-dependent diabetes mellitus (NIDDM). Fasting hyperinsulinemia occurred in only one participant, who was in the IGT group. Hypertriglyceridemia and low high density lipoprotein (HDL) occurred in four persons, none of whom had hyperinsulinemia. Persons in the NIDDM and IGT groups had decreased beta cell function compared to persons in the NGT group, but did not have increased peripheral insulin resistance as estimated from the OGTT data. CONCLUSIONS: Our data demonstrated that in this cohort of elderly hypertensive participants with a high prevalence of central obesity, impaired glycemic control was common, but was not associated with fasting hyperinsulinemia or peripheral insulin resistance. Furthermore, we conclude that syndrome X essentially did not occur in these participants and postulate that the primary etiology for their impaired glycemic control is beta cell dysfunction. Further research is needed to elucidate these relationships.

A comparison of once-daily atenolol and metoprolol using office and ambulatory blood pressure monitoring.

The authors compared the relative safety and efficacy of changing treatment from once-daily atenolol to metoprolol in patients with essential hypertension. A parallel-group randomized clinical trial was conducted in two phases: a 4-week baseline single-blind phase using atenolol 50 mg, followed by a 4-week randomized double-blind treatment phase using either atenolol 50 mg or metoprolol 100 mg administered once daily at noontime. Patients with well-controlled hypertension already prescribed 50 mg of atenolol (with or without the addition of a diuretic) for control of hypertension were selected for participation from the outpatient hypertension clinic of the Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania. Seated blood pressure (BP) and pulse were obtained during the baseline phase and during the randomized treatment phase. Twenty-four-hour ambulatory BP monitoring was performed once during the baseline phase and once during the randomized treatment phase, near the end of each 4-week period. There were no within- and between-treatment differences in office systolic and diastolic BP. There was a slight increase in pulse (average = 5.2 beats/minute; P = .02) for those participants treated with metoprolol. For within-treatment groups, the ambulatory BP data showed no significant differences in systolic and diastolic BPs, except for an increase in morning diastolic BP for those randomized to metoprolol (average = 6.2 mm Hg; P = .01). For between-treatment groups, the metoprolol arm had a higher morning systolic BP (P = .01), a higher morning diastolic BP (P = .03), and a higher nighttime heart rate (P = .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension, creatinine, and plasma renin activity in heart transplant recipients.

Development of de novo hypertension in a large proportion of orthotopic heart transplant recipients receiving cyclosporine has previously been reported. This hypertension is characterized by a persistence of increased peripheral resistance, sodium retention, and loss of nocturnal decline in BP. Vascular nephropathy with plasma renin activity (PRA) elevation from cyclosporine (CsA) may also be major factor in the progress of hypertension. To investigate this hypothesis, observations of BP, creatinine (Cr), and PRA were made in 144 heart transplant recipients followed for up to four and a half years. Median Cr was 133 mumol/l. Average diastolic BP and mean PRA values were significantly higher in patients with Cr greater than or equal to the median. Cr and PRA were significantly correlated (r = 0.4; P less than 0.001) in recipients with Cr greater than or equal to 133 mumols/l but not in those with Cr less than 133 mumols/l. In a selected subsample of heart transplant recipients with repeated Cr and PRA values, Cr and PRA appeared to increase longitudinally after transplant. These data are derived from a case series of patients managed on a variety of antihypertensive agents (excluding ACE inhibitors) needed to control the persistent hypertension.

Primary care within the VA: the firm model.

Many of the VA medical centers are reorganizing total care across a continuum that includes outpatient, inpatient, long-term, and home based care, into interdisciplinary firms. The goals of reorganization are to improve patient access to care and continuity of care, to improve housestaff education by assigning a specific panel of patients for the residents to follow longitudinally in a variety of situations supervised by the same mentors, and to enhance research in primary care issues. Preliminary results show increased patient satisfaction and improvements in both quality of care and increased efficiency in its delivery. Many large health care organizations might be expected to reorganize care delivery around a similar interdisciplinary team concept.

Systolic hypertension in the elderly.

Historically diastolic blood pressure (BP) rather than systolic BP has been regarded clinically as the more important component related to subsequent hypertensive morbidity and mortality, and treatment has thus been directed towards lowering the diastolic BP. Observational studies across many different populations have related cerebrovascular disease and death more to the systolic BP, which appears selectively to increase as the population ages. Isolated systolic hypertension (ISH), therefore, may be more prevalent as westernized societies become older. Those affected with ISH suffer a two- to fivefold increase in rates of stroke and ischemic heart disease compared to normotensives. Currently no clinical trials data exist for ISH showing the efficacy of antihypertensive therapy upon final morbidity and mortality, but a large-scale multicenter clinical trial, the Systolic Hypertension in the Elderly Program (SHEP), is currently underway in the United States. Results are expected in the early 1990s. If the results of this trial confirm the efficacy of treating ISH, the therapeutic challenge of ISH will be to selectively decrease systolic BP without undue side effects.

Relative benefits of different antihypertensive drugs in the prevention of vascular complications.

Large-scale clinical trials of antihypertensive drugs that have shown a reduction in morbidity and mortality used the classic step-care treatment design, initiating treatment with a diuretic. Long-term morbidity and mortality reports comparing the newer classes of agents with the traditional antihypertensive agents have not been completed. A recent meta-analysis of 13 randomized, controlled clinical trials of hypertension showed that 18 elderly people, but two to four times as many younger people, needed to be treated for 5 years to prevent one cerebrovascular or cardiac event. Any head-to-head comparisons of one class of antihypertensive agent with another in the prevention of vascular complications will require very large cohorts, even of elderly people, to show a difference. Such trials are ongoing or being planned, but their results will not be available before the next century.

Hypertension following orthotopic cardiac transplantation.

It seems established that hypertension, to some degree, is a frequent consequence of cardiac transplantation. The hypertension occurs de novo and is not related to whether hypertension was present in association with the heart disease that led to the need for transplantation. The etiology of this hypertension is multifactorial and varies depending on the time that has ensued after transplantation. Acutely, it is primarily a problem related to intravascular volume expansion and persistently increased systemic vascular resistance. Although it may be modest in severity, it seems to be particularly resistant to therapy with most antihypertensive drugs. Moreover, the total "hyperbaric impact" of the hypertension is rendered greater because the blood pressure and heart rate in these patients with denervated hearts fails to show the usual 10 to 15 percent fall when recumbent/asleep at night, which occurs in normotensive individuals and in most with hypertension of other etiologies. The major factor in the persistence of the hypertension through the later stages post-transplantation appears to be the cyclosporine that is used as an immunosuppressive. Although cyclosporine has been the major contributor to reduced rejection in these individuals, and to their increasingly prolonged survival, it inevitably produces slowly progressive impairment of renal function. The damage to the kidney is reflected both in tubular as well as glomerular and vascular damage, with a steady fall in glomerular filtration and a rise in creatinine. From our studies it appears that the renal alterations are associated with a gradual rise in plasma renin activity and angiotensin II, which perhaps further damages the kidney and causes persistence of the increased systemic vascular resistance. The use of lower doses of cyclosporine during the ischemic phase in the kidney that immediately follows surgery and of reduced doses over time, often with azathioprine added, seems to minimize the renal damage, or at least to stabilize it and to slow progression of the renal dysfunction and hypertension. Treatment of the hypertension with conventional drugs has definite but limited value. Diuretics and vasodilators have been the mainstay of our approach during the early phases of the hypertension but our recent data indicate that ACE inhibitors may become relatively specific in management during the later phases of the post-transplantation period as PRA levels rise in response to vascular damage by cyclosporine. ACE inhibitors have inherent dangers that require careful monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)

Coronary heart disease mortality and sudden death: trends and patterns in 35- to 44-year-old white males, 1970-1990.

Trends in coronary heart disease mortality and sudden death were studied in 35- to 44-year-old white male residents of Allegheny County, Pennsylvania. Deaths coded as any cardiac or vascular disease, diabetes, unexplained sudden death, and other rubrics were eligible for investigation, and the cause of death was validated by physicians examining multiple data sources about the deaths. During 1970-1990, 1,424 white male deaths were investigated, with 903 validated as coronary heart disease. In that time span, white male coronary heart disease mortality fell from 93.4 to 36.7 per 100,000 population per year, a 60% decline. Little proportionate change was seen in characteristics of the deaths, which were predominantly sudden and out-of-hospital. Diabetes mellitus history increased proportionately over time, largely because diabetics' mortality rates, unlike those of all other subgroups, did not fall. These observations support the contention that the decline in coronary heart disease mortality relates to risk factor modification more than to improvements in the treatment of coronary heart disease. Differences in death certification practices must be considered when interpreting and comparing vital statistics data.