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[Hypertrophy of left ventricular myocardium as modifiable risk factor: novel possibilities of correction].

Hypertrophy of left ventricular myocardium observed in 15-20% of patients with arterial hypertension is an independent factor which elevates considerably risk of complications of hypertension (ischemic heart disease, chronic heart failure, ventricular arrhythmias). Regression of left ventricular hypertrophy (LVH) at the background of hypotensive therapy is associated with additional lowering of cardiovascular risk. This should be taken into consideration in selection of a hypotensive preparation. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are believed to have most pronounced ability to cause reverse development of LVH. It has been shown in recently finished PIXEL trial that administration of fixed combination of ACEI perindopril and diuretic indapamide reduced LVH more effectively than monotherapy with high doses of ACEI enalapril and provided better blood pressure control. Therefore in a patient with hypertension and LVH it is expedient to consider combined therapy with ACEI and diuretic including use of their fixed combinations as treatment of choice.

Angiotensin-Converting Enzyme Inhibitors↗

[Variations of the cardiac rhythm during drug treatment. Presuppositions of cardiac protection].

In the present study, the authors assessed the therapeutic efficacy of three drugs, each representing a different pharmacological class; i.e. indapamide as diuretic, doxazosin as alpha 1-blocker, and slow-release nifedipine as calcium blocker. The action of these drugs on blood pressure and on the reduction of both atrial and ventricular ectopic beats was observed taking into account the dynamic evolution of the heart as a result of increased blood pressure. This evolution goes from normal heart to hypertrophic and subsequently to dilated heart with attendant alterations of cardiac rhythm.

Adrenergic alpha-Antagonists↗

[Home blood pressure monitoring in addition to office blood pressure determination is useful in patients with systolic hypertension before their inclusion into a drug trial].

OBJECTIVE: In patients with uncontrolled systolic hypertension, to estimate the value of home blood pressure monitoring in addition to office blood pressure for inclusion in a trial. METHODS: 80 patients with systolic hypertension, defined as SBP > or =140 mmHg and pulse pressure > or =60 mmHg, were treated for 4 weeks with a thiazide diuretic at usual dose (25 mg HCTZ or 1.5 mg indapamide or methyclothiazide 5 mg). Blood pressure was measured using an automatic monitor (Omron M6) at office and at home in the 3 days prior the visit. Subjects with an uncontrolled hypertension were included in the second part of the trial only if there fulfilled inclusion criteria: office SBP > or =140 mmHg and home SBP > or =135 mmHg (mean of 18 measurements obtained on 3 consecutive days) and office pulse pressure > or =60 mmHg. RESULTS: After 4 weeks with diuretic treatment, 62% of patients fulfilled 3 criteria and were included in the second part of the trial. It was observed 76% of patients with office SBP > or =140 mmHg, 72% with office pulse pressure > or =60 mmHg and 70% with both office SBP and PP criteria. However, only 67% of patients had home SBP > or =135 mmHg. Discrepancy between office and home SBP was observed and subjects with a white coat hypertension was noticed in 14% and masked hypertension in 5%. CONCLUSION: If patients with systolic hypertension have to be included into a drug trial because there are uncontrolled, home blood pressure monitoring in addition to office blood pressure is a very useful criteria for inclusion because misclassifications due to white coat or masked hypertension is frequent in these patients.

Aged↗

[Noliprel efficiency in patients with hypertension].

Monotherapy prevailing nowadays in the treatment of essential hypertension is one of the causes of not sufficiently effective hypotensive therapy. Combination of antihypertensive drugs is a more efficient strategy as synergism of applied medications may be reached and not high doses may develop less adverse effects. 30 patients (17 men and 13 women, average age is 51 years) with hypertension which have not taken antihypertensive drugs from different reasons have been prescribed Noliprel being a combination of Perindopril and Indapamid in low doses (2.00 mg and 0.625 mg accordingly) for 3 months. The study conducted by the author differs from the trials on Noliprel effectiveness by its more profound investigation of the echocardiography parameters and cardial hemodynamics. The measurement of left ventricular myocardium mass index, wall and interventricular septal thickness and many other echocardiographic parameters have been studied. Noliprel has already demonstrated good antihypertensive activity in 83.3% of patients after one month therapy. 16.7% of patient increased dose intake to two pills per day and after 3 months of the therapy their arterial pressure reached the target level. The author considered in details the dynamics of echocardiography parameters during therapy with Noliprel. Noliprel is a highly effective and safe medication which positively influences on processes of myocardium remodeling and is metabolically neutral. No side effects have been seen during the treatment with this medication by the patients having been treated.

Adult↗

The diuretic effect of metipamide and its relationship to body weights in rats.

Metipamide [M], a new Czechosclovak diuretic with a hypotensive effect, was administered in a dose of 20 mg/kg (about 500-fold the therapeutic dose) I. for three weeks to rats of both sexes kept under normal conditions in groups of five, and II, for eight days to single male rats in metabolic cages. The animals' body weight and food and water consumption were studied and in the second series their daily faeces, urine and urinary sodium and potassium excretion were measured. Rats kept in individual cages were also given indapamide (I), the first diuretic with a separate hypotensive effect used in other countries, in a dose of 20 mg/kg. The experimental animals' body weight was significantly lower than that of controls with the same food consumption and their water intake and urine flow were much higher, especially after M. Sodium (and to a lesser extent potassium) excretion was raised at the outset of administration of both the test substances and again after the 5th to 8th dose, but only after M. After three weeks' administration of M. SNa, SK and S(osm) values were within normal limits. but after eight days the serum electrolytes and the osmolality of the serum were markedly reduced. After I. these values were normal. We conclude that the strong diuretic effect of M is not the only cause of lower body weight in rats.

Animals↗

[Diuretic and antihypertensive activity of azosemide].

The results of a study conducted using a new loop diuretic, Azosemide, on a group of 45 patients suffering from hypertension and oedema are reported. Thirty patients were studied in an open trial and in association with other drugs. The remaining 15 exclusively hypertensive patients, were studied in a controlled trial against Indapamide. The patient's standing and recumbent arterial pressure was monitored and all were given periodic weight checks. In the 1st group, Azosemide brought about a significant reduction in arterial pressure, without modifying body weight, but caused considerable weight loss (from 71 to 64 kg) (P less than 0,01) in the oedema patients without altering arterial pressure. In the 2nd group of hypertensive patients, a significant fall in arterial pressure (from 166 to 138 mmHg) was observed, most notably after Azosemide treatment. None of the patients revealed side effects, or alterations in laboratory parameters. It is therefore suggested that Azosemide--given its effectiveness and ease of application--is particularly useful for the diuretic treatment of hypertensive and oedematous patients.

Body Weight↗

Different blood pressure responses to diuretic treatment in normotensive subjects with and without a family history of hypertension.

The possibility that the familial background for hypertension may influence the blood pressure response to diuretic treatment was evaluated in 14 normotensive subjects with negative and 14 normotensive subjects with positive family history of hypertension. Under control conditions, blood pressure, heart rate, body weight, urinary sodium and potassium, plasma sodium, potassium, creatinine, norepinephrine, epinephrine, renin and aldosterone levels did not differ between the two study groups. Each subject received chlorthalidone, 100 mg/day, or indapamide, 2.5 mg/day for eight weeks. Compared with control values, blood pressure was decreased during diuretic treatment in subjects with positive (P less than 0.05), but not in those with negative family history for hypertension. Diuretic-induced decreases in plasma potassium (P less than 0.005), increases in plasma renin activity and aldosterone (P less than 0.005), and a tendency towards higher plasma norepinephrine levels were not different between the two study groups. These findings suggest that the familial background of hypertension may, at least in part, determine the blood pressure response to diuretic treatment.

Adult↗

Hyperlipidemia of diuretic therapy.

Hyperlipidemia is a widely acknowledged side effect of thiazide diuretic therapy, but it is often dismissed as a short-term effect of high-dose therapy. Large clinical trials usually show no lipid change during late follow-up. These large trials use intention-to-treat analysis which masks the lipid effect. On-treatment analysis regularly reveals the persistence of hyperlipidemia during 4-5 years of treatment. Studies of low-dose thiazide therapy give conflicting results. Meta-analysis of these studies reveals hyperlipidemia of a milder degree than with high-dose thiazide treatment. However, a trade-off of effects is apparent because systolic blood pressure is lowered less well with low doses. Thus, thiazide effects on blood pressure and lipids are dose-dependent. Similar meta-analysis of indapamide 2.5 mg daily shows no adverse lipid effect and a lowering of blood pressure equivalent to 50 mg of hydrochlorothiazide. Regarding clinical events, low-dose thiazide treatment exerts primary prevention of coronary heart disease but provides less benefit against stroke and congestive heart failure than does high-dose therapy. Thus, an evidence-based therapeutic strategy for further reducing cardiovascular risk is as follows: initiate antihypertensive therapy with low-dose diuretics. Add beta-blockers and dihydropyridine-type calcium channel blockers for further antihypertensive effect, if needed. Hypertension resistant to a 3-drug regimen should be treated with high-dose thiazides. Lipids should be monitored at each step and treated with diet and statin drugs to maintain lipid goals. Risk factor control is an old concept that has yet to be effectively implemented.

Adrenergic beta-Antagonists↗

Drug-drug interactions among elderly patients hospitalized for drug toxicity.

CONTEXT: Drug-drug interactions are a preventable cause of morbidity and mortality, yet their consequences in the community are not well characterized. OBJECTIVE: To determine whether elderly patients admitted to hospital with specific drug toxicities were likely to have been prescribed an interacting drug in the week prior to admission. DESIGN: Three population-based, nested case-control studies. SETTING: Ontario, Canada, from January 1, 1994, to December 31, 2000. PATIENTS: All Ontario residents aged 66 years or older treated with glyburide, digoxin, or an angiotensin-converting enzyme (ACE) inhibitor. Case patients were those admitted to hospital for drug-related toxicity. Prescription records of cases were compared with those of controls (matched on age, sex, use of the same medication, and presence or absence of renal disease) for receipt of interacting medications (co-trimoxazole with glyburide, clarithromycin with digoxin, and potassium-sparing diuretics with ACE inhibitors). MAIN OUTCOME MEASURE: Odds ratio for association between hospital admission for drug toxicity (hypoglycemia, digoxin toxicity, or hyperkalemia, respectively) and use of an interacting medication in the preceding week, adjusted for diagnoses, receipt of other medications, the number of prescription drugs, and the number of hospital admissions in the year preceding the index date. RESULTS: During the 7-year study period, 909 elderly patients receiving glyburide were admitted with a diagnosis of hypoglycemia. In the primary analysis, those patients admitted for hypoglycemia were more than 6 times as likely to have been treated with co-trimoxazole in the previous week (adjusted odds ratio, 6.6; 95% confidence interval, 4.5-9.7). Patients admitted with digoxin toxicity (n = 1051) were about 12 times more likely to have been treated with clarithromycin (adjusted odds ratio, 11.7; 95% confidence interval, 7.5-18.2) in the previous week, and patients treated with ACE inhibitors admitted with a diagnosis of hyperkalemia (n = 523) were about 20 times more likely to have been treated with a potassium-sparing diuretic (adjusted odds ratio, 20.3; 95% confidence interval, 13.4-30.7) in the previous week. No increased risk of drug toxicity was found for drugs with similar indications but no known interactions (amoxicillin, cefuroxime, and indapamide, respectively). CONCLUSIONS: Many hospital admissions of elderly patients for drug toxicity occur after administration of a drug known to cause drug-drug interactions. Many of these interactions could have been avoided.

Aged↗

A decade of developments in diuretic drug therapy.

New diuretics introduced into clinical medicine during the past decade include potent new loop diuretics such as bumetanide and piretanide, the uricosuric indanyloxyacetic acid derivative indacrinone, and a new generation of sulfamoyl diuretics such as indapamide and xipamide, which are recommended primarily for the treatment of hypertension. Pharmacokinetic studies of individual diuretics have demonstrated that the diuretic and natriuretic responses to the newer agents generally follow the plasma drug concentration-time curves and urinary drug excretion rates. Therapeutic monitoring can therefore be achieved in most patients with edema or hypertension by close clinical observation and laboratory analysis of plasma electrolyte and creatinine concentrations and urinary electrolyte excretion rates. Interest in the mechanisms involved in the renal and extrarenal vascular actions of the newer diuretics has led to a better understanding of how changes in venous compliance, peripheral vascular resistance, and renal blood flow distribution may contribute to the overall therapeutic response to these agents, especially in patients with severe congestive heart failure, renal insufficiency with low glomerular filtration rates, and hypertension with cardiorenal complications. Adverse reactions to modern diuretics, which are mainly an extension of their renal pharmacodynamic effects, have proved to be minimal, provided that the dosage is adjusted to meet but not exceed individual patient requirements. However, the long-term consequences of prolonged periods of diuretic-induced alterations in plasma potassium levels, and metabolic effects that include elevated blood lipids, are still under investigation.

Diuretics↗

Drug-induced alteration of endothelial permeability in the rat aorta. Potential consequences on the vessel wall.

UNLABELLED: We recently reported that some diuretics affect capillary permeability in the normotensive rat. In the present study, we explore the effect of selected antihypertensive drugs administered orally during 10 days, on Evans blue (EB) extravasation within the wall of the thoracic (TA) and abdominal aorta (AA) obtained from spontaneously hypertensive rats (SHR). Description of the EB method has been previously reported. Daily doses (mg/kg) of captopril (CAP: 3.0), perindopril (PER: 0.3), nifedipine (NIF: 1.0), clentiazem (CLE: 0.1), hydralazine (HYD: 0.5), furosemide (FUR: 0.5), cicletanine (CIC: 2.0), hydrochlorothiazide (HCZ: 0.5), and indapamide (IND: 0.04) resulted in comparable blood pressure reduction. Percent changes in EB tissue concentration (measured in ug/g dry tissue) was increased by 24% in both the TA and AA in the untreated SHR. CAP reduced by half EB leakage in the TA, while PER decreased EB extravasation 16% below baseline values. Both angiotensin converting enzyme inhibitors failed to normalize EB leakage in the AA. The calcium channel blockers also normalized EB extravasation in the two segments of the aorta, except that CLE was without effect in the AA. HYD normalized EB leakage in the TA, but not in the AA. All diuretics tested reduced EB extravasation by 48 to 58% below baseline values in the TA, whereas CIC only normalized EB leakage. None of the diuretics affected EB extravasation in the AA of the SHR. IN CONCLUSION: 1-the two segments of the aorta were similarly affected in the SHR; 2-despite comparable effect on blood pressure, treatment of the SHR was associated with different responses in the TA and AA; 3-within a given class of drugs, different effects are observed on EB.

Animals↗

Stroke prevention: management of modifiable vascular risk factors.

Stroke prevention is a crucial issue because (i) stroke is a frequent and severe disorder, and (ii) acute stroke therapies that are effective at the individual level have only a little impact in term of public health. Stroke prevention consists of the combination of 3 strategies: an optimal management of vascular risk factors, associated when appropriate with antithrombotic therapies, carotid surgery, or both. Primary prevention trials have shown that reducing blood pressure in hypertensive subjects reduces their vascular risk, including stroke. The association of perindopril plus indapamide reduces the vascular risk in patients who have had a stroke or TIA during the last 5 years, irrespective of their baseline blood pressure. Lowering serum cholesterol with statins or gemfibrozil in patients with hypercholesterolemia or coronary heart disease (CHD), reduces the risk of stroke. However, no trial of cholesterol-lowering therapy has been completed in stroke patients. A strict control of high cholesterol levels should be encouraged, because of benefits in terms of CHD. Statins should be prescribed for stroke patients with CHD, or increased cholesterol levels. Cigarette smoking is associated with an increased risk of stroke and should be avoided. Careful control of all risk factors, especially arterial hypertension in type 1 and type 2 diabetics is recommended, together with a strict glycemic control to reduce systemic microvascular complications. Estrogens prescribed in hormone replacement or oral contraceptive therapies are not recommended after an ischemic stroke. It is also recommended to reduce alcohol consumption and obesity, and to increase physical activity in patients at risk for first-ever or recurrent stroke. An optimal management of risk factors for stroke is crucial to reduce the risks of first-ever stroke, recurrent stroke, any vascular event after stroke and vascular death. One of the major public health issues for the coming years will be to focus more on risk factor recognition and management.

Alcoholism↗

Atherosclerotic Risk Factors in Patients with Ischemic Cerebrovascular Disease.

Aggressive treatment of atherosclerotic risk factors can substantially reduce stroke risk in patients with a history of stroke or transient ischemic attack. Data from several recent large clinical trials provide convincing evidence of benefit for a number of specific therapies directed at this population. The authors recommend treatment with ramipril alone or perindopril plus indapamide regardless of blood pressure, provided there is no contraindication. For patients already taking a different angiotensin- converting enzyme (ACE) inhibitor, the authors do not routinely switch agents. The authors recommend use of simvastatin 40 mg per day in patients with a total cholesterol level of 135 mg/dL or greater, provided no contraindication exists. The authors also recommend consideration of gemfibrozil in patients with isolated low high- density lipoprotein levels. In patients with diabetes mellitus, tight glycemic control has not been shown to reduce macrovascular complications such as stroke, but does reduce microvascular complications. However, diabetics should receive especially aggressive treatment of other vascular risk factors. There is no role for post-menopausal hormone replacement therapy in prevention of stroke. Weight loss for overweight patients, regular exercise, and a diet rich in fruits, vegetables, cereals, and fish, as well as low in fat and cholesterol, should be a standard recommendation for this group of patients. Treatment with folic acid, B(6), and B(12) for patients with elevated homocysteine appears rational, though this is unproven. However, there is no benefit to vitamin E, vitamin C, or beta-carotene supplementation. Smokers should stop. For every 43 smokers who quit, one stroke is prevented. Moderate consumption of alcohol (one to two drinks a day) may be beneficial, but heavy alcohol use (more than five drinks a day) increases stroke risk.

Journal Article↗

Insights into intrarenal sites and mechanisms of action of diuretic agents.

Effective diuresis requires both sufficient glomerular filtrate and adequate delivery of the diuretic drug to the lumen of the renal tubule. Diuretics will not "force open" the kidney. Diuretics that work primarily in the proximal tubule include osmotic diuretics (e.g., mannitol), diuretics that interfere with the adenyl cyclase system (e.g., xanthines), and those which inhibit carbonic anhydrase (e.g., acetazolamide). Some thiazide and thiazide-like diuretics have a secondary site of action in the proximal tubule based on either carbonic anhydrase inhibition or other mechanisms, such as inhibition of sodium phosphate reabsorption. The diuretics that work primarily in the medullary diluting segment of the loop of Henle, furosemide and ethacrynic acid, block the active reabsorption of chloride and interfere with the tubular reabsorption of free water. The exact mechanism remains unknown. These diuretics tend to have a "high ceiling," to be potent and rapidly acting, and to have a short duration of effect. They are excellent for the treatment of severe fluid overload or pulmonary edema but are not ideal for the treatment of uncomplicated hypertension. Furosemide is a sulfonamide derivative; ethacrynic acid can be used in patients who are allergic to sulfa drugs. Diuretics that work primarily in the cortical diluting segment include the thiazides and thiazide-like drugs. They inhibit sodium transport by an undetermined mechanism. Most of them seem to reach a dose-response plateau beyond which little additional effect is gained by increasing the dose. Most of them appear to lose efficacy as the glomerular filtration rate decreases, except for metolazone and indapamide. The thiazides are most commonly used to treat hypertension. Diuretics that work primarily in the distal tubule and collecting tubule include the aldosterone inhibitor spironolactone and two drugs that impair tubular reabsorption of sodium by direct action, triamterene and amiloride. These drugs are primarily used for their potassium-sparing effect.

Animals↗

Vascular smooth muscle cell proliferation and its therapeutic modulation in hypertension.

The increased growth potential of vascular smooth muscle cells (VSMCs) represents one of the crucial anomalies responsible for the development of essential hypertension, diabetic macroangiopathy, and atherosclerosis. The exaggerated response to growth factors of VSMC from spontaneously hypertensive rats (SHRs) persists in culture when compared with normotensive Wistar-Kyoto control rats, indicating an intrinsic defect in the hypertension-producing mechanism. This greater proliferation is characterized by two intermediate phenotypes: (1) accelerated entry into the S phase of the cell cycle, which results from hyperresponsiveness to epidermal growth factor and platelet-derived growth factor, and (2) abnormal contact inhibition. The enhanced expression of transforming growth factor beta 1 (TGF-beta 1) messenger ribonucleic acid in SHRs precedes this altered contact inhibition, and only VSMCs from SHRs respond to exogenously added TGF-beta 1 at a high cell density, which suggests that abnormal TGF-beta 1 autoregulation may be implicated in the second phenotype. Platelets contain major growth factors for VSMC. Platelet extracts from hypertensive and diabetic patients present augmented growth-promoting activity on VSMCs, which is most evident when both diseases occur simultaneously. Growth-promoting activity may be further influenced by antihypertensive therapy. This growth-promoting activity is increased by hydrochlorothiazide but not by indapamide, atenolol, or captopril in diabetic hypertensive and nondiabetic hypertensive patients. In conclusion, VSMCs in hypertension manifest an intrinsic growth defect that is modulated by extrinsic platelet growth factors and antihypertensive drugs.

Animals↗

Pathogenesis and treatment of hypertension associated with diabetes mellitus.

The pathogenesis of hypertension associated with diabetes mellitus (DM) involves an interplay of hereditary and acquired mechanisms. A familial trait for essential hypertension appears to be a risk factor for the development of both hypertension and nephropathy in type I DM and coexists commonly with impaired insulin sensitivity, relative hyperinsulinemia, and dyslipidemia, which can already be detected before the appearance of hypertension, obesity, or upper abdominal redistribution of body fat. The latter finding helps explain the frequent development of hypertension as well as dyslipidemia and/or type II DM in given individuals. Obesity is an important factor promoting these complications. Type I or II DM but not uncomplicated essential hypertension is characteristically accompanied by excess body Na+. This abnormality complements a tendency toward vascular hyperreactivity and a presumably morphologic and functional vasculopathy, thereby promoting the pathogenesis of hypertension in diabetic patients. For the treatment of hypertension in diabetic patients, nonpharmacologic measures are indispensable. If drugs are needed, angiotensin-converting enzyme (ACE) inhibitors and some but not all calcium antagonists are the preferred agents. Monotherapy or a combination of these drug types allows effective blood pressure control in most diabetic patients without further metabolic impairment; ACE inhibitors even tend to improve glucose control. Ketanserin may be a potential alternative, and if a diuretic is also needed, the metabolically neutral indapamide is a reasonable choice. If these agents do not allow satisfactory blood pressure highly selective beta 1-blockers or alpha 1-blockers may be introduced as a second choice. In diabetic patients with nephropathy, effective antihypertensive therapy can reduce proteinuria and slow the progression of the nephropathy; ACE inhibitors may improve diabetic proteinuria even at unchanged systemic blood pressure levels. Unless diuretics are needed for reasons other than hypertension, the treatment of diabetic patients with thiazides or loop diuretics in conventional dosage should probably be avoided until clarification of their influence on prognosis. Nevertheless, whether and to what extent other agents and nonpharmacologic measures can modify the prognosis in diabetic patients is also unclear, and the approach to antihypertensive therapy is therefore still largely empiric.

Antihypertensive Agents↗

Antihypertensive strategy: a current and prospective review.

The efficacy of antihypertensive therapy in reducing cardiovascular complications has been clearly demonstrated in the last 20 years. Antihypertensives are particularly useful in the reduction of cerebrovascular complications which decrease by 60% on average in clinical trials on the treatment of mild and severe hypertension. After the first clinical trials, the 1978 World Health Organization Experts Committee recommended the classic stepped-care (SC) approach with diuretics and beta blockers as first-step agents. Other antihypertensive drugs, such as reserpine, centrally acting agents and vasodilators could be used in the next steps if blood pressure control was not achieved. Both diuretics and beta blockers have been widely used and the SC regimen has contributed to the better control of arterial hypertension in the community. The SC regimen has given general practitioners easy guidelines with which to treat hypertensive patients. There are many reasons for modifying the classic SC approach. Prescription of antihypertensive drugs at high doses should be avoided and the use of new agents, such as calcium antagonists and angiotensin-converting enzyme inhibitors, is recommended. Demographic trends have brought about an increase in the aged population and, consequently, an increase in the proportion of elderly hypertensives. These patients present particular problems in long-term management, among which are a high frequency of other associated diseases and an important number of adverse effects caused by the classic antihypertensive drugs. Nevertheless, diuretics are still useful in the treatment of hypertension, either as a monotherapy regimen or in association with other drugs. New diuretics, such as indapamide, have a very interesting pharmacologic profile with considerably fewer metabolic side effects on plasma cholesterol and glucose levels.

Adrenergic beta-Antagonists↗

Role of metabolic risk factors in cardiovascular prognosis of systemic hypertension.

There is an increasing awareness of the need to manage multiple risk factors in hypertensive patients, and of possible adverse metabolic effects of antihypertensive drugs which may counteract their ability to reduce the risk of cardiovascular disease. Data collected from the Austin Hospital Hypertension Clinic support previous observations that the incidence of cardiovascular risk factors such as plasma lipid abnormalities are high in hypertensive patients, and although it is becoming easier to control blood pressure in these patients, modification of other risk factors is difficult. The use of diuretics in doses lower than those conventionally prescribed has been advocated as a means of reducing the adverse metabolic effects. However, data from this study suggest that although low-dose hydrochlorothiazide therapy (25 to 50 mg/day) may be as effective as conventional doses of captopril in reducing blood pressure, adverse metabolic effects on plasma potassium, glucose and uric acid levels remain a problem. Indapamide, a relatively new diuretic when used at a fixed dose (2.5 mg/day), appears to be devoid of significant adverse metabolic effects and is a useful alternative to thiazide diuretics. An integrated approach to the management of multiple cardiovascular risk factors is important in hypertensive patients and should include non-pharmacologic methods and the selection of antihypertensive drugs that do not have adverse metabolic effects.

Antihypertensive Agents↗