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Analysis of the available evidence indicates that diuretics do not increase coronary heart disease morbidity and mortality. The multiclinic trials supporting the cardiotoxicity hypothesis are few in number and flawed in design. The majority of the trials, including the well designed trials, indicate no excess of coronary heart disease (CHD) events in diuretic-treated patients compared with those given other drugs or placebo. Recent studies indicate no increase in cardiac arrhythmias after diuretic treatment. Also, although depletion of intracellular potassium and magnesium occurs in patients with congestive heart failure even without diuretics, intracellular concentration of these ions is not significantly reduced by diuretics in patients with uncomplicated hypertension. Modest elevations of serum cholesterol may occur during the first 6 to 12 months of treatment with thiazide diuretics. However, after this time these elevations fall to or below the pretreatment level. The fall may be greater in patients receiving other drugs but the differences are small and their clinical significance is questionable. The incidences of hyperglycaemia and diabetes were only minimally increased in long term clinical trials while the importance of hyperinsulinism and insulin resistance in causing CHD remains unproven in patients. Thiazides remain, therefore, a safe and effective treatment for patients with hypertension.
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PMID:Adverse effects of diuretics. 141 93

To understand the content of ambulatory family practice and find effective ways to improve clinical service, education and research in the Department of Family Medicine of Kaohsiung Medical College Hospital, we surveyed 14,064 patients from Jan. 1984 to Feb. 1991 and analysed (a) their basic demographic data including sex, age, insurance type, source and residential district and (b) clinical health problems covering 25,679 diagnoses and 148,994 diagnostic visits. Clinical health problems were recorded by the ICHPPC-2 code system. Results of basic demographic survey were as follow: 49.1% of patients was male and 50.9% female; 58.9% fell in the age group of 16-40 years and 22.4%, 12.0% and 6.7% of patients fell into the age groups of 41-65, under 16 and over 65 years respectively; 62.8% was insured usually by labor insurance and 26.9% had no insurance; the commonest referrals were other patients, colleagues, company personnel, doctors, media ... etc.; 58.8% lived in Kaohsiung City and 19.6% in Kaohsiung county. As for clinical health problems, the data showed that the commonest thirty diagnoses encountered at our clinic accounted for 69.3% of 25,679 diagnoses and the commonest ten diagnoses in descending order were medical health examination, acute URI, abdominal pain, uncomplicated hypertension, prophylactic immunization, hepatitis B carrier, back pain, anxiety disorder, viral hepatitis and irritable bowel syndrome. By calculating the average value of each diagnosis in a sample of 148,994 diagnostic visits to evaluate the habits of practice, we found that the commonest ten diagnostic visits at clinic in descending order were diabetes mellitus, hypertension involving target organ, uncomplicated hypertension, gout, hyperthyroidism, duodenal ulcer, tuberculosis, lipid metabolism disorder, other peptic ulcer and depressive disorders; all were chronic diseases. We concluded it was very important and helpful for the development of family medicine program and primary care unit to understand the content of their own ambulatory practice.
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PMID:[The content of ambulatory family practice in Kaohsiung Medical College Hospital]. 156 Apr 75

Careful consideration of all relevant scientific evidence and a critical assessment of data quality show that thiazide diuretics are not cardiotoxic. Of 12 reported trials only two recorded more coronary heart disease events in thiazide-treated patients than in controls. One of these two was a subgroup of a larger study (Heart Attack Prevention in Primary Hypertension, HAPPHY) which found no difference between thiazide-treated and beta-blocker-treated patients. The other, the Oslo study, was too small to allow valid conclusions. Results from a subgroup in the Multiple Risk Factor Intervention Trial (MRFIT) that appeared to supply evidence for thiazide-related cardiotoxicity are suspect when examined critically. Further evidence from 24- to 28-h ECG monitoring does not support the hypothesis that thiazide diuretics, either in the presence or absence of hypokalemia, increase the frequency or severity of ventricular arrhythmias. Reports of a thiazide-induced intracellular magnesium deficiency as a cause of ventricular arrhythmias have also not been confirmed; the development of arrhythmias in acute myocardial infarction appears to be due to an increase in catecholamine levels rather than hypokalemia. There appears to be little evidence to support the assumption that long-term use of thiazide diuretics aggravates or accelerates atherosclerosis of the coronary arteries; any fall in serum cholesterol appears to be transient. For the great majority of patients with uncomplicated hypertension, without a previous myocardial infarction, congestive heart failure, diabetes mellitus or gout, thiazide diuretics appear to be both safe and effective antihypertensive agents.
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PMID:The cardiotoxicity of thiazide diuretics: review of the evidence. 221 84

Hypertension is a major modifiable risk factor for cardiovascular diseases. After decades of improvement, population surveys demonstrate disturbing downward trends in the rates of awareness, treatment, and control of this disorder in recent years. Over this same time period, there has been a slight increase in the incidence of strokes, and a steady rise in the incidence of end-stage renal disease and the prevalence of congestive heart failure, conditions in which hypertension plays a prominent role. Results of recent studies support the possibility that lifestyle modifications may be effective for prevention of hypertension. Treatment of established hypertension involves lifestyle modifications and drug therapies designed to control blood pressure and reduce overall cardiovascular risk. Both threshold blood pressure levels for initiating drug therapy and goal blood pressure levels with treatment are individually determined based on the presence or absence of additional cardiovascular risk factors and hypertension target organ injury or clinical cardiovascular disease. Recent clinical trials support the value of lower goal blood pressures for patients with diabetes, heart failure, and renal disease. The presence or absence of comorbid conditions often determines specific drug choices. Diuretics and beta-blockers remain the drugs of choice in uncomplicated hypertension. Additional studies confirm the benefits of treating isolated systolic hypertension in the elderly. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provides a practical, evidence-based resource to help health care providers meet the public health challenges of preventing and controlling hypertension.
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PMID:A review of the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 1019 76

Hypertension is a significant and prevalent risk factor for the development of cardiovascular disease and target organ damage. The urgency of treatment of high blood pressure depends on the level of blood pressure elevation and the presence of coexistent risk factors for cardiovascular disease. Likewise, the level to which blood pressure is reduced is not restricted to the definition of high blood pressure but instead depends on the underlying disease. Diabetes and renal insufficiency, for example, require blood pressure goals below those that are traditionally defined. In the absence of contraindications, beta-blockers and diuretics are still recommended as first-line agents for treatment of uncomplicated hypertension. Calcium channel antagonists also may reduce mortality. In patients with diabetes, ACE inhibitors are effective first-line agents in type 1 and type 2 diabetic patients who are hypertensive or have microalbuminuria. ACE inhibitors may be beneficial in patients with nondiabetic renal insufficiency as well. Calcium channel antagonists may have some effect in retarding progression of diabetic nephropathy although a recent trial found a higher incidence of death as a secondary endpoint in hypertensive diabetic patients who were treated with calcium channel antagonists. Beta-blockers seem to be safe and well tolerated in patients with mild to moderate intermittent claudication, although patients with rest pain or limb ischemia have not been studied. Beta-blockers should not be used in patients with asthma. Dihydropyridine calcium channel antagonists are the preferred treatment of hypertension in patients with Raynaud's but should be avoided in patients with severe gastroesophageal reflux disease. NSAIDs, particularly piroxicam and indomethacin, raise mean blood pressure by approximately 5 mm Hg, enough to consider a change of either NSAID or antihypertensive to one that is not as affected by NSAIDs. Cyclosporine A can induce hypertension by its vasoconstrictive effects, particularly on the kidney. Calcium channel antagonists may antagonize this vasoconstriction while allowing the clinician to reduce the dose of cyclosporine A required to achieve its immunosuppressive effect.
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PMID:Evaluation and treatment of hypertension. 1046 27

The goals of antihypertensive therapy are to lower blood pressure and prevent end-organ damage without side effects, which affect quality of life. The antihypertensive drugs, regardless of class, all lower blood pressure, but they vary in their mechanisms of action, side-effect profiles, suitability for patients with other comorbid conditions, and ability to protect against the long-term sequelae of hypertension. The Sixth Report of the Joint National Committee on Prevention, Evaluation, and Treatment of High Blood Pressure (JNC-VI) recommends diuretics and beta-blockers as first-line therapy for uncomplicated hypertension, with diuretics also being strongly preferred for patients with isolated systolic hypertension or hypertension and heart failure and beta-blockers being strongly preferred for patients who have had a myocardial infarction (MI) and those with hypertension and angina, atrial tachycardia, or atrial fibrillation. Because angiotensin-converting enzyme (ACE) inhibitors have been shown to be cardioprotective and renoprotective in patients with diabetes or impaired left ventricular (LV) function, the JNC-VI recommends them as first-line therapy in patients with diabetes with proteinuria, heart failure, and MI complicated by LV dysfunction. It recommends calcium channel blockers for hypertensive patients with angina, long-acting dihydropyridines for those with isolated systolic hypertension, and the nondihydropyridines for those with atrial tachycardia or fibrillation, diabetes, and proteinuria. The angiotensin II receptor blockers (ARBs) share many of the organ-protective effects of ACE inhibitors when studied in animal models. They are effective in lowering blood pressure and have a very benign side-effect profile; however, these agents have not been available long enough to ascertain their efficacy in protecting against long-term complications.
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PMID:Clinical overview of antihypertensive classes--clinically relevant differences: myths or facts? Based on a presentation by Alan H. Gradman, MD. 1097 60

Therapeutic goals for the treatment of hypertension and the ability of various angiotensin-converting-enzyme (ACE) inhibitors to meet these goals are presented. The 1997 Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) does not recommend ACE inhibitors for first-line therapy in the treatment of hypertension; however, these guidelines do identify compelling indications for ACE inhibitor therapy, including diabetes mellitus (type 1) with proteinuria, heart failure, or previous myocardial infarction with systolic dysfunction. Since the JNC-VI guidelines were developed, the results of a prospective randomized clinical trial in patients with uncomplicated hypertension have demonstrated that ACE inhibitor therapy is as effective as conventional treatment in the prevention of cardiovascular morbidity and mortality. In hypertensive patients with diabetes, therapy with captopril, enalapril, fosinopril, or ramipril has resulted in significant reductions in cardiovascular events. In addition, tight blood pressure control with an ACE inhibitor has resulted in a greater reduction in the risk of macrovascular and microvascular complications of diabetes than was seen with less tight control. Recent study results support broader use of ACE inhibitors for hypertension than was recommended in the JNC-VI guidelines.
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PMID:Role of angiotensin-converting-enzyme inhibitors in the treatment of hypertension. 1103 17

Both the Joint National Committee and the British Hypertension Society recommend b-blockers and diuretics as first-line therapy in the treatment of uncomplicated hypertension. As a result, many clinicians will also prescribe these drugs in the treatment of patients with hypertension and coexistent disease (unless they are specifically contraindicated), even though they may not always be the most beneficial choice. This review aims to examine factors that should be taken into consideration when choosing appropriate antihypertensive therapy. Particular attention is given to treatment options in two special patient groups, the elderly and patients with co-morbid diabetes, as these groups have an increased risk of developing cardiovascular complications. In response to the increasing evidence base from large-scale trials, the article concludes that cardiovascular risk factors, coexisting disease, concomitant medication and age should all be taken into account when choosing antihypertensive therapy.
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PMID:Considerations for drug therapy in hypertension. 1121 16

More than 50% of patients with mild uncomplicated hypertension will need combination therapy to reach target blood pressure, as defined by the Joint National Committee. This percentage is even higher in hypertensive patients with diabetes, renal impairment and congestive heart failure in whom target blood pressures are lower. Combination therapy of angiotensin converting enzyme inhibitor and low dose diuretic offers distinct advantages in the treatment of essential hypertension. The two drug classes may have a synergistic effect on hypertensive target organ disease and blood pressure. Triple therapy with a calcium antagonist may be needed to achieve blood pressure control in more severely hypertensive patients.
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PMID:The choice of first-line therapy: rationale for low-dose combinations of an angiotensin converting enzyme inhibitor and a diuretic. 1171 46

Despite dramatic improvements in the management of hypertensive cardiovascular disease, much remains to be accomplished. Arterial stiffness, through its effects on central aortic pressure, is a key determinant of increased cardiovascular risk. Increased pulse pressure is a late manifestation of increased arterial stiffness. What is needed is a simple, reliable, non-invasive method of detecting early disturbances in central artery stiffness at a time when therapeutic intervention can be most beneficial. Currently, intervention studies support initiating antihypertensive therapy in uncomplicated hypertension when systolic blood pressure > or = 160 mmHg, whereas the benefit of treating systolic blood pressure of 140-159 mmHg, the largest subset of persons with hypertension, has yet to be tested in controlled trials. Further studies are needed to determine the optimal target goal for blood pressure reduction in both uncomplicated hypertension and in hypertension complicated by diabetes, coronary heart disease, or renal disease. Angiotensin converting enzyme inhibitors may provide selective cardiac and renal protection beyond their blood pressure-lowering effect in the presence of specific cardiovascular disease and/or diabetes. In contrast, there is as yet no definitive answer as to the relative benefit of blood pressure lowering versus specific drug effects in minimizing cardiovascular events in uncomplicated hypertension. Although there has been a recent increase in hypertension awareness and treatment, only a small percentage of affected individuals are being treated to goal. Hypertensive cardiovascular disease represents a world-wide public health challenge that can be solved only by new innovative measures aimed at both prevention and treatment.
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PMID:Blood pressure and cardiovascular disease: what remains to be achieved? 1171 48


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