Hypertension: are beta-blockers and diuretics appropriate first-line therapies?

OBJECTIVE: To review the existing data on the use of diuretics or beta-blockers as first-line therapy for the treatment of mild to moderate hypertension, and to examine the issues surrounding the impact of these classes as well as the angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers (CCBs), alpha-blockers, and alpha-beta-blockers on cardiovascular risk factors and cardiovascular morbidity and mortality. DATA SOURCES: A MEDLINE search of applicable articles on antihypertensive therapies and their impact on morbidity and mortality. In addition, a MEDLINE search of relevant articles regarding cardiovascular risk factors and the influence of the various antihypertensive therapies on these parameters. DATA SYNTHESIS: The literature was evaluated with regard to outcome. Trials examining the impact of antihypertensive pharmacotherapy, primarily with diuretics and beta-blockers, have shown them to decrease the incidence of stroke by 33-50 percent. However, their effect on coronary heart disease has been disappointing, showing only a 14 +/- 5 (mean +/- SD) percent decrease. Examination of numerous clinical trials assessing the impact of the various antihypertensive therapies on cardiovascular risk factors, including blood pressure, plasma lipids, diabetic control/insulin sensitivity, and left ventricular hypertrophy was done. The classes included beta-blockers, diuretics, alpha-blockers, ACE inhibitors, and CCBs; the results show a diversity of effect. Diuretics and beta-blockers tend to worsen cardiovascular risk status, whereas the alpha-blockers, ACE inhibitors, and CCBs all show a beneficial effect. CONCLUSIONS: Diuretics and beta-blockers can effectively reduce cerebrovascular morbidity and mortality, but have a limited effect on reducing cardiovascular disease, especially myocardial infarction. This may be explained, at least in part, by the negative, or lack of positive, effect on individual patients' overall cardiovascular risk status.     

ON THE CHOICE OF REGRESSION VARIABLES IN NONLINEAR DATA RECONCILIATION

Reconciliation of process data constrained by multicomponent material balance equations can be accomplished by a regression calculation in which either total flow rates and compositions (primary variables) or total and component flow rates (secondary variables) are used as the regression variables. It is shown by means of computer simulation experiments that the choice of secondary variables for regression can adversely affect the performance of an associated gross error detection algorithm. The principal effect is an increased tendency of the algorithm to make Type I errors     

Issues surrounding tight glycemic control in people with type 2 diabetes mellitus

OBJECTIVE: To review the prospective evidence surrounding the issue of tight glycemic control in people with type 2 diabetes mellitus and resultant long-term complications. DATA SOURCE: Conference proceedings and a MEDLINE search (1966-February 1998) identified pertinent English-language publications on type 2 diabetes in humans. Key search terms included insulin resistance, diabetes mellitus, non-insulin-dependent, macrovascular complications, microvascular complications, and intensive glycemic control. STUDY SELECTION: Selection of prospective epidemiologic and clinical studies were limited to those focusing on the management of type 2 diabetes. All articles with pertinent information relevant to the scope of this article were reviewed. DATA SYNTHESIS: The pathophysiology of type 1 and type 2 diabetes differ; however, both share chronic complications that significantly affect morbidity and mortality. People with type 1 diabetes have an absolute deficiency of insulin, whereas people with type 2 diabetes have varying degrees of insulin resistance and an inadequate compensatory insulin secretory response. The Diabetes Control and Complications Trial (DCCT) has clearly indicated that intense control of blood glucose in type 1 diabetes prevents and slows the progression of microvascular (i.e., retinopathy, nephropathy) and neuropathic complications. The Kumamoto study showed similar results in nonobese patients with type 2 diabetes. Intense insulin therapy in both populations has proven advantageous, thus supporting a common pathophysiologic process for the microvascular and neuropathic complications. Trends were seen toward fewer macrovascular (atherosclerotic disease) complications in the intensive insulin arm of the DCCT. Conversely, trends were seen toward an increase in macrovascular complications in the VA Cooperative study in people with type 2 diabetes using intensive insulin therapy. This may suggest a discordance in the pathophysiology of macrovascular disease between type 1 and type 2 diabetes. Additionally, it remains uncertain whether tight glycemic control prevents the onset or slows the progression of macrovascular disease. Two studies (the University Group Diabetes Program and the Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes) to date have examined pharmacotherapy options for patients with type 2 diabetes and resultant macrovascular complications. It has yet to be determined whether any therapeutic intervention will decrease the morbidity and mortality of macrovascular disease in this population. CONCLUSIONS: In type 2 diabetes, limited prospective evidence does support tight glycemic control to help prevent or slow the progression of microvascular and neuropathic complications. It is uncertain whether tight glycemic control decreases macrovascular complications and which pharmacotherapeutic agent(s) is/are the best options. However, therapy that improves glucose control in combination with aggressive risk factor management should be initiated and enforced in patients with type 2 diabetes in an effort to reduce long-term complications.