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Coronary heart disease and treatment of hypertension. Some Oslo Study data
Insights
Antihypertensive drug therapy in the Oslo Hypertension Study showed increased coronary heart disease mortality. Alpha-adrenergic blockers like prazosin may offer a safer alternative by improving lipid profiles.
Area of Science:
- Cardiology
- Pharmacology
- Public Health
Background:
- The Oslo Hypertension Study, initiated in 1972, followed 785 healthy men aged 40-49 with mild hypertension.
- Participants were randomized into a drug-treated group or an untreated control group, with an average follow-up of 66 months.
Purpose of the Study:
- To evaluate the long-term effects of antihypertensive drug therapy on cardiovascular complications and mortality.
- To explore reasons for the potential failure of certain antihypertensive drugs to prevent coronary heart disease.
Main Methods:
- Randomized controlled trial comparing drug treatment versus no treatment for mild hypertension.
- Analysis of cardiovascular events, including stroke, aneurysm, and coronary events, and total mortality over 10 years.
- Investigation into the metabolic effects of different antihypertensive drug classes on lipid and carbohydrate metabolism.
Main Results:
- Complications like stroke and aneurysm were exclusively observed in the untreated control group.
- The drug-treated group experienced more coronary events, leading to no significant difference in overall cardiovascular complications.
- Coronary heart disease mortality was significantly higher in the drug-treated group after 10 years (14 vs. 3).
Conclusions:
- Standard antihypertensive drug therapy, particularly diuretics and beta-blockers, may not prevent coronary heart disease and could potentially increase mortality.
- Adverse effects on lipid and carbohydrate metabolism by diuretics and beta-blockers are implicated.
- Alpha-adrenergic blockers, such as prazosin, show promise due to their neutral or beneficial effects on blood lipid profiles, reducing cholesterol and triglycerides.
Abstract:
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.