Sodium depletion increases platelet and plasma catecholamines in hypertensive men.

The catecholamine content in blood platelets is considerably higher than that in plasma, and platelet catecholamines must be taken up from plasma, since blood platelets lack enzymes for catecholamine synthesis. However, it is unknown whether platelets take up and store catecholamines during physiological in vivo increments in plasma catecholamines. Previously untreated 50-year-old men (n = 17) with mild to moderate essential hypertension were given a low sodium diet for 2 weeks. Urinary excretion of sodium decreased from 201 +/- 11 (SE) to 24 +/- 5 and 19 +/- 4 mmol/24 hr after 1 and 2 weeks, respectively. During the first week, the blood platelet concentration of norepinephrine increased from 27.2 +/- 2.9 to 39.6 +/- 4.7 pg/mg (p less than 0.005) and venous plasma norepinephrine increased from 3.7 +/- 0.4 to 5.6 +/- 0.5 pg/ml (p less than 0.005), and venous plasma dopamine increased from 26 +/- 4 to 41 +/- 5 pg/ml (p less than 0.05). During the second week, both plasma and platelet norepinephrine and dopamine remained elevated. Platelet epinephrine showed a small increase from baseline to the second week (p less than 0.05), but no concomitant increase in plasma epinephrine occurred. Thus, sodium depletion increases both platelet and plasma catecholamines and blood platelets may take up catecholamines in vivo. Platelet catecholamine content may be an integrated measure of plasma catecholamine concentrations during variations caused by sodium depletion.

Increased plasma vasopressin in low renin essential hypertension.

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lovastatin alone and in combination with cholestyramine on serum lipids and apolipoproteins in heterozygotes for familial hypercholesterolemia.

We have studied the effect of lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl coenzyme A reductase), alone and in combination with the bile acid sequestrant cholestyramine on lipid parameters in 30 heterozygous patients with familial hypercholesterolemia (FH) during a 20-week open trial. Lovastatin 40 mg bid (twice daily) decreased significantly total serum cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides and apolipoprotein B by 36%, 45%, 29% and 11%, respectively, while high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I were increased significantly by 16% and 37%, respectively. These data are consistent with a reduction in both the number of LDL particles and in their cholesterol content. Addition of cholestyramine 4 g bid caused a significant further decrease in total serum cholesterol and LDL-cholesterol to a total of 43% and 61%, respectively. The addition of 4 g bid or 8 g bid of cholestyramine caused only minor changes in the other lipid parameters. No effect was found by these drugs on Lp(a) lipoprotein level. We conclude that lovastatin alone or in combination with a small dose of cholestyramine normalizes the lipid profile in most FH heterozygotes.

Comparison of effects on lipid metabolism of antihypertensive drugs with alpha- and beta-adrenergic antagonist properties.

Elevated blood cholesterol levels are a major cause of coronary heart disease. High-density lipoprotein cholesterol is regarded as a protective cholesterol fraction that is negatively associated with the incidence of coronary heart disease. Thus, the ratio of high-density lipoprotein to total cholesterol levels is an expression of the total atherogenicity--the higher the ratio, the lower the risk of coronary heart disease. There is a sharp contrast between alpha- and beta-adrenergic blockers with regard to their effect on the profile of blood lipids. In most studies, alpha blockers increased high-density lipoprotein cholesterol levels and decreased serum triglyceride levels. In addition, alpha blockers generally reduce total serum cholesterol levels. On the other hand, most beta blockers reduce serum levels of high-density lipoprotein cholesterol and increase serum triglyceride levels. European clinical trials recently investigated the effects of alpha blockers and beta blockers on blood lipids in a total of 104 and 281 patients with hypertension, respectively. On the average, selective alpha blockade increased the high-density lipoprotein cholesterol:total cholesterol ratio by 11.3 percent and reduced serum triglyceride levels by 11.4 percent. In contrast, the selective and nonselective beta-adrenergic blockers atenolol, metoprolol, and propranolol reduced that ratio by 11.7 percent and increased serum triglyceride levels by 25.8 percent. This difference between alpha and beta blockers may significantly influence the risk profile of coronary heart disease and should be given strong consideration when choosing drug therapy for hypertensive patients.

Effect of alpha- and beta-blocker therapy on blood lipids: European experience.

Although hypertension is a well-established coronary risk factor, controlled, randomized hypertension drug trials have failed to show a definite preventive effect on the incidence of coronary heart disease. Possible adverse metabolic effects, particularly on blood lipids, of some commonly used antihypertensive drugs have been investigated. During the Oslo Study on the treatment of mild hypertension, which was not specifically designed to study the effect on lipids, a decrease in serum high-density lipoprotein cholesterol and an increase in serum triglycerides was observed with a combination of propranolol and hydrochlorothiazide. Therefore, special trials were designed specifically to study the effect of various antihypertensive drugs on blood lipids. Propranolol reduced serum high-density lipoprotein cholesterol (13 percent) and the cholesterol ratio [high-density lipoprotein cholesterol:(low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol)] by 15 percent and increased total serum triglycerides by 24 percent. Prazosin significantly (p less than 0.01) reduced total serum cholesterol, (9 percent) low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol (10 percent), and total triglycerides (16 percent), whereas the cholesterol ratio increased by 7 percent. The reduction in high-density lipoprotein cholesterol with propranolol plus prazosin was less than that with propranolol alone. Pindolol (with a high sympathomimetic activity) did not significantly change total cholesterol, low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or total triglycerides. Prazosin plus pindolol reduced serum low-density lipoprotein cholesterol plus very low-density lipoprotein cholesterol. The observed reductions in serum high-density lipoprotein cholesterol and the cholesterol ratio with oxprenolol were 11.5 percent and 13.7 percent, respectively, and with atenolol 16.7 percent and 19.2 percent, respectively, whereas total serum triglycerides were increased by 14.9 percent with oxprenolol and 17.9 percent with atenolol. Data provided by other European groups comparing the effect of antihypertensive treatment on lipid metabolism are also reviewed.

Coronary heart disease and treatment of hypertension. Some Oslo Study data.

The Oslo Hypertension Study began in 1972; patients were followed for an average of 66 months (range: 60 to 78). A total of 785 healthy men, aged 40 to 49, with mild hypertension was randomly assigned to either a drug-treated group or to an untreated control group. Hydrochlorothiazide was used alone in 36 percent of patients, in combination with propranolol in 26 percent, and with methyldopa in 20 percent. Other drugs, including combinations with hydrochlorothiazide, were used in 18 percent. A total of 95 percent of patients in the drug-treated group received hydrochlorothiazide. Complications of hypertension such as stroke and aneurysm occurred only in the control group. Coronary events were more numerous in the drug-treated group; thus, the total incidence of cardiovascular complications did not significantly differ between the treated and untreated groups. After five and 10 years, total mortality was the same in both groups. However, the coronary heart disease mortality rate at 10 years was significantly greater in the drug-treated group than in the untreated control group (14 versus three, p less than 0.01). This article presents possible reasons for the failure of antihypertensive drug therapy to prevent coronary heart disease. The adverse effect of diuretics and beta-adrenergic blockers, both on lipid and carbohydrate metabolism, is contrasted with the effect of the alpha-adrenergic blocker prazosin, which has been shown to have no adverse effect on the blood lipid profile. In a short-term trial that was part of the Oslo Study, prazosin was found to reduce total serum cholesterol by 9 percent, low-density lipoprotein and very-low-density lipoprotein cholesterol by 10 percent, and total triglycerides by 16 percent. All these changes are statistically significant.

Oslo Study Diet and Antismoking Trial. Results after 102 months.

The five year (60-month) results from the Oslo Study Diet and Antismoking Trial were published in the Lancet in December 1981. The trial involved 1,232 healthy men, aged 40 to 49 years, at high risk for coronary heart disease, with serum cholesterol values in the range of 7.5 to 9.8 mmol/liter (enzymatic method: 6.9 to 9.0, mean value 7.8 mmol/liter). Eighty percent of the men were daily cigarette smokers at the start of the study, and all participants were normotensive, i.e., systolic blood pressure was less than 150 mm Hg. Subjects were randomly assigned to either a control or intervention group. Follow-up visits were scheduled every six months for the intervention group and yearly for the control group. Once the trial was completed, the regular six-month follow-up visits were discontinued, but eight to nine years (96 to 108 months) after the start of the trial, participants were called for a new follow-up. Risk factors were recorded, and clinical events were diagnosed according to the same procedure as during the trial. The mean serum cholesterol levels in the intervention group remained unchanged three years after the end of the trial, but the cholesterol levels in the control group declined. Daily cigarette smoking increased in the intervention group but remained stable in the control group. At the new follow-up, the difference in incidence of fatal and nonfatal myocardial infarction and sudden coronary death was the same as at the end of the trial three years earlier, yielding significant differences between the two groups for sudden death, total coronary death, and total coronary events. Although the study was not designed to show differences in total mortality, this difference became marginally significant, with 19 deaths in the intervention group and 31 in the control group. It is concluded that although net differences in risk factors between the two groups had been reduced during the three years after the regular intervention period, the significant difference in coronary events and sudden death was maintained.

Serum triglycerides and serum uric acid in untreated and thiazide-treated patients with mild hypertension. The Oslo study.

Levels of serum lipids, uric acid and body weight are reported from a controlled trial of drug treatment of middle-aged men with uncomplicated mild hypertension. The results come from 300 men after three years of follow up; 150 men in the treatment group and 150 men in the control group. The treatment has been standardized starting with hydrochlorothiazide alone and adding alpha methyldopa when necessary. In case of side effects, alpha methyldopa was replaced with propranolol. Pretreatment results demonstrated a strong covariation among body weight, uric acid and triglycerides. In the entire treatment group, there was no significant change in triglycerides after three years (increase from 1.85 to 2.02 mM/liter, P greater than 0.05). Cholesterol was also unchanged. Further analysis showed that certain patients reacted with an increase in triglycerides during treatment: those prone to a distinct increase in uric acid and those gaining weight. Those who needed combination therapy (having the highest pretreatment blood pressure) showed most of the increase in triglyceride and uric acid. In the group treated with hydrochlorothiazide alone, the triglycerides were unchanged. However, those selected from this group with a distinct increase in uric acid also showed an increase in triglycerides. The treatment increased the pretreatment positive correlation between uric acid and triglycerides.

Serum glucose levels during long-term observation of treated and untreated men with mild hypertension. The Oslo study.

Serum glucose levels, triglyceride levels, and body weight are reported from a controlled drug trial in men, aged 40 to 49, with uncomplicated mild hypertension. The drug treatment started with hydrochlorothiazide alone, and methyldopa was added when necessary. If side effects occurred, methyldopa was replaced by propranolol. No detailed advice about diet, smoking, or weight reduction was given to any group. The untreated control subjects had a small increase in serum glucose levels during five years, from 6.08 to 6.21 mmol/liter. Those treated with hydrochlorothiazide alone and those treated with hydrochlorothiazide plus methyldopa had a small increase in serum glucose levels of the same order as that in the control subjects. However, those receiving the thiazide/propranolol combination experienced a sizeable increase in glucose levels, from 5.96 to 6.53 mmol/liter (p less than 0.001). This increase was significantly greater than the increase in the other groups (p less than 0.001). The thiazide/propranolol group also showed a significant increase in serum triglyceride levels (p less than 0.05). There was no difference in serum potassium levels in the different drug groups. The results indicate that moderate thiazide doses do not have significant effects on serum glucose levels in this age group. Propranolol in combination with thiazide seems to increase the level of serum glucose.

Risk of fatal stroke according to blood pressure level: an 18-year follow-up of the Oslo Study.

OBJECTIVE: To determine how blood pressure level predicts the incidence of fatal stroke. DESIGN: The Oslo Study is a prospective cohort study of preventive and epidemiological aspects of cardiovascular disorders in middle-aged men. Of 25,915 men invited, 16,209 aged 40-49 years attended the screening. A 7% random sample of men aged 20-39 years were also invited to attend. METHODS: The screening started in May 1972 and the analysis presented is an 18-year follow-up for fatal strokes. Men with a history of stroke were excluded from the analyses. RESULTS: Of 16,173 men with no history of stroke 85 died from stroke. Results from Cox proportional hazards regression analysis confirm diastolic (DBP) and systolic blood pressure (SBP) as strong independent risk factors of fatal stroke, with DBP being the stronger predictor. Analyses of risk of fatal stroke by quintile values show SBP to give significantly increased risk from the third quintile (136 mmHg), and DBP from the fifth quintile (95 mmHg) relative to the first quintile. No levelling off at highest levels can be seen when analysing decile values. No J-shape of the curve was evident. Men on drug treatment for hypertension with no stroke history (n = 440) had 4.7-fold (crude) and 2.8-fold (adjusted for age and DBP) the rate of stroke mortality of men not on drug treatment for hypertension. CONCLUSION: DBP was a stronger predictor than SBP, with increasing risk from the fifth quintile of DBP and the third quintile of SBP. Men on drug treatment for hypertension at screening were at increased risk during the follow-up period, indicating that their treatment did not sufficiently reduce their risk of stroke.

Decreased platelet-free dopamine and unchanged noradrenaline and adrenaline in essential hypertension.

The content of free-catecholamines in blood platelets is much higher than in plasma and platelet catecholamines must be taken up from plasma, since platelets lack the enzymes for catecholamine synthesis. There is some evidence that platelet catecholamine content under certain circumstances may be an integrated measure of plasma catecholamine concentrations over time. Platelet-free catecholamines were therefore assayed in 18 untreated patients with essential hypertension and in 16 normotensive control subjects. Mean platelet-free dopamine in the hypertensive group was 3.7 +/- 0.4 pg/mg platelet weight, i.e. significantly less than the 6.5 +/- 0.9 pg/mg found in the normotensive (p less than 0.005). Platelet contents of noradrenaline and adrenaline did not differ. Decreased platelet-free dopamine and unchanged platelet noradrenaline and adrenaline persisted after adjustment for increased body weight in the hypertensive group. Although the reasons for decreased platelet-free dopamine in the hypertensive group remain unknown, this finding may add to previous result showing facilitated release of granular contents from blood platelets in patients with essential hypertension. Our data do not support platelet levels of free-catecholamines to be a marker of increased sympathetic tone in essential hypertension.

Does increased platelet release normalize during anti-hypertensive treatment?

Blood platelet function was evaluated in 10 men, all 50 years old, with untreated, mild hypertension. Each patient was examined four times: At the beginning of the study, after 5 weeks on placebo treatment, after the following 5 weeks on propranolol 160 mg daily, and finally after a second period of 5 weeks on placebo. At baseline the plasma level of the platelet release product beta-thromboglobulin (BTG) was 41.6 (30.5-57.0) micrograms/l (median and 95% confidence interval). During the first placebo period BTG was normalized to 21.0 (14.1-25.9) micrograms/l. While systolic blood pressure and heart rate fell during beta-adrenergic receptor blockade, BTG remained unchanged throughout the rest of the observation periods. Platelet size increased significantly during treatment with beta-blocker. The present study indicates that the normalization of elevated platelet function which previously has been reported to occur during anti-hypertensive drug therapy, may be explained by patient adaptation to the blood sampling procedure.

Increased plasma noradrenaline during severe sodium restriction does not stimulate platelet release in essential hypertension.

Seventeen 50-year old hypertensive men, previously untreated with blood pressure 157 +/- 4/110 +/- 2 mmHg (means +/- SE) were given a low sodium diet for 2 weeks. During the second week, the diet was supplemented with potassium. The urinary Na+/K+ excretion ratio changed from 2:1 to 1:4 and 1:11, respectively. Sympathetic noradrenergic tone increased considerably during the first week. Thus, venous plasma noradrenaline increased from 254 +/- 22 to 347 +/- 28 pg/ml (p less than 0.001) and arterial concentration from 253 +/- 36 to 317 +/- 42 pg/ml (n = 10, p less than 0.001). No significant change was observed in sympathetic adrenal tone as reflected by normal plasma adrenaline in venous (42 +/- 5 vs 43 +/- 6 pg/ml, ns) or arterial blood (71 +/- 10 vs 82 +/- 15 pg/ml, n = 10, ns) or in venous plasma concentration of the blood platelet release product beta-thromboglobulin (BTG) (50 +/- 8 vs 43 +/- 5 ng/ml, ns). During the second week sympathetic noradrenergic tone remained highly significantly elevated compared to baseline but still no change in plasma adrenaline or plasma BTG was found. Thus, whereas sodium depletion did increase plasma noradrenaline concentration markedly in these hypertensive men, no change in adrenaline concentration was observed, and blood platelet release reaction was unchanged. Plasma noradrenaline within the physiological concentration range does not seem to serve as a regulator of in vivo platelet function.

Coronary risk factors and their pathway of action through coronary raised lesions, coronary stenoses and coronary death. Multivariate statistical analysis of an autopsy series: the Oslo Study.

From 1972 to 1973, 16,202 Oslo men, aged 40 to 49 years, were examined for cardiovascular disease and coronary heart disease (CHD) risk factors. This report describes the results of autopsy examinations from 204 of 471 men who died in this cohort with regard to associations between selected risk factors and (1) raised coronary atherosclerotic lesions (RL), (2) coronary artery stenosis, and (3) CHD death. Total serum cholesterol and blood pressure levels were positively associated with all 3 measures of coronary atherosclerosis and its complications, both in univariate and multivariate analyses, whereas high-density lipoprotein (HDL) cholesterol was highly and inversely related. Triglyceride levels, cigarette smoking, social class and physical activity at work and at leisure were not significantly associated with either of the 3 measures. When RL was added to the model with stenosis as the dependent variable, the risk factors no longer appeared as independent; this is consistent with the hypothesis that these factors, when significant, work through the development of RL to produce stenosis. HDL cholesterol was the only risk factor independently and significantly associated with CHD death when RL or stenosis or both were put into the model for CHD. This points to the possibility of HDL cholesterol also working through mechanisms other than the prevention of RL and stenosis toward CHD death.

Oslo Hypertension Study.

The Oslo Hypertension Study started in 1972 and lasted for 66 (range 60-78) months. A total of 785 healthy men, aged 40 to 49 years, with mild hypertension were randomised to a drug-treated group and to an untreated, control group. The drugs used for treatment were hydrochlorothiazide alone in 36%, hydrochlorothiazide and propranolol in 26%, hydrochlorothiazide and methyldopa in 20%, and other drugs in 18%. A total of 95% in the drug-treated group received hydrochlorothiazide. Pressure complications, such as stroke and aneurysms, only occurred in the control group. Coronary events were more numerous in the drug-treated group, so that the total incidence of cardiovascular complications did not significantly differ between the treated and untreated groups. After 5 and 10 years, total mortality was found to be the same in both groups. However, the 10-year coronary heart disease mortality was significantly higher in the drug-treated group than in the untreated controls (14 v 3, p less than 0.01). Possible reasons for the failing effect of drug treatment of hypertension on coronary heart disease is discussed, and attention is drawn to the adverse effect of diuretics and beta-adrenergic blockers, both on lipid and carbohydrate metabolism. This is in contrast to the alpha-adrenergic blocker, prazosin, which has been shown to improve the blood lipid profile.

Mortality in relation to smoking history: 13 years' follow-up of 68,000 Norwegian men and women 35-49 years.

A total of 44,290 men and 24,535 women aged 35-49 have been followed with respect to different causes of death during 13.3 years on average. A detailed history of smoking, together with other important risk factors, were recorded in a standardized way. Compared with the classical American and British studies, the excess mortality for the smokers was largely the same for the majority of causes. The exceptions were cerebrovascular mortality and suicides and accidents, which were more strongly related to smoking in this study. Furthermore, men who smoked only pipe, had nearly the same coronary heart disease mortality as men who smoked only cigarettes. The same applies to lung cancer mortality. Among men who had quit cigarette smoking, the coronary heart disease mortality decreased with time since quitting to almost the level of the never cigarette smokers after 5 years or more.

Quality-adjusted meta-analysis of the hypertension/coronary dilemma.

Primary investigators of randomized drug trials in hypertension were invited to rate quality of such trials. The intention of the survey was to ask if antihypertensive drug therapy reduces incidence of coronary heart disease (CHD) in hypertensive patients. Response was obtained for 7 of the 11 invited investigators, covering 69% of patients and 75% of CHD cases. Principal component analysis was used to construct a quality score based on answers to 12 questions along visual analog scales. The score correlated well with the answer to a global question of overall quality given by the raters. No systematic tendency toward favoring one's own trial could be demonstrated, therefore, all raters have contributed to the rating. The trials with the highest rated quality to answer the research question were Systolic Hypertension in the Elderly Program (SHEP), Australian National Blood Pressure Study, Medical Research Council, Veterans Administration, and European Working Party of Hypertension in the Elderly. The large Heart Detection and Follow-up Program (HDFP) trial was rated at 11th place among the trials with a score of < 40% of the SHEP. The small trials performed in the 1960s were placed at the bottom of the ranking list. Because SHEP is the only trial without diastolic hypertension, results were given with and without SHEP results. When incorporating the quality score into a meta-analysis of CHD outcome, results were dependent on whether SHEP was included or not. For diastolic hypertension only, the effect of therapy was estimated to be about 8% for all higher quality studies, whereas inclusion of the lower quality HDFP changed it to 14%. When isolated systolic hypertension trial was pooled with the others, no major relation to quality rating was observed. A 14% CHD preventive efficacy was established when pooling the three top quality studies. This stayed unchanged until HDFP at rank 11 was included raising this estimate to 16%. Inclusion of the two latest published trials in the elderly, the Medical Research Council trial of treatment of hypertension in older adults and the Swedish Trial in Old Patients with hypertension, did not change this overall estimate of 16% (standard error = 3.8%). It is concluded that if all randomized drug trials in hypertension had the same treatment efficacy, the estimated CHD prevention would be in the range of 15%. Subgroup analyses revealed no relationship to age, but a difference in efficacy was shown depending on whether the trials were performed in the United States or elsewhere. Also, patients at higher risk levels showed better benefit than lower risk patients.

Increased erythrocyte magnesium in never treated essential hypertension.

In the present study we aimed at evaluating the intracellular concentrations of magnesium, potassium and sodium in 50-year-old, otherwise healthy white men with never treated, essential hypertension (n = 12) and in normotensive control subjects (n = 12) matched for age, sex, race, height, weight and smoking habits. Intraerythrocyte magnesium was significantly increased in the hypertensive group (P less than .001) and correlated positively and significantly to blood pressure in the total group (P less than .01). The intracellular potassium to sodium ratio tended to be lower in the hypertensive group (P less than .05). Thus, the present study supports increased intracellular magnesium probably unrelated to intracellular potassium-sodium imbalance in never treated, essential hypertension.

Effects of oral antihypertensive agents on blood lipid levels.

The Lipid Research Clinic trials established conclusively that lowering serum cholesterol reduces the incidence of coronary heart disease. Yet a number of clinical trials have demonstrated that many pharmacological agents commonly used to lower blood pressure also adversely affect serum lipid levels. Recent studies of prolonged use of beta-blockers and diuretics have failed to show that these agents have any clear primary preventive effect on coronary heart disease; in a few cases, these agents were believed to pose a greater risk of coronary heart disease than no antihypertensive treatment at all. These observations suggest that a reappraisal of current therapeutic schemes is in order. Because coronary heart disease is known to have many causes, primary preventive therapy must logically go beyond the relatively simple goal of lowering blood pressure. The metabolic effects of antihypertensive drugs, particularly on blood lipids, should also be taken into account. These effects could be of special clinical significance in relatively young patients, for whom the long-term risk of developing coronary heart disease is of major concern. This review discusses recent clinical trials examining the effects on lipids of diuretics, beta-blockers, and selective alpha-adrenoceptor blocking agents.

Effects of antihypertensive drugs on lipid metabolism.

Despite the well-established correlation between coronary heart disease (CHD) and hypertension, conventional antihypertensive therapy with diuretics and beta-adrenergic blockers has failed to provide protection against CHD. A possible explanation for this failure is the unfavorable effect such drugs have on lipid metabolism. To compare the lipid profiles of commonly used antihypertensive drugs, a survey was made of selected studies from the literature. Diuretics and selective and nonselective beta-blockers were found to have adverse effects on blood lipids. Beta-blockers with intrinsic sympathomimetic activity, labetalol, methyldopa, and calcium channel blockers are lipid neutral, whereas alpha-adrenergic blockers seemed to have a favorable effect on lipid metabolism. Controlled clinical trials with drugs that have no adverse effects on lipid metabolism are needed to establish the long-term clinical importance of such agents.