Metabolic abnormalities of hypertension. A lesson in complexity.

In this issue, Reaven and coworkers 1 report on carbohydrate and lipid abnormalities in yet another experimental model of hypertension, the Dahl rat. Whether salt-sensitive or salt-resistant, animals of this strain are hyperinsulinemic and dyslipidemic. This finding strengthens the contention that in essential hypertension, metabolic disorders such as reduced glucose tolerance, dyslipidemia, and hyperinsulinemia/insulin resistance are inherent features rather than incidental findings. To what extent does this concept apply to human essential hypertension? The notion that in patients with high blood pressure, both carbohydrate intolerance and lipid changes are more frequent than expected on the basis of chance alone is not new and emerges consistently from shrewd clinical observation. More or less consciously, however, clinicians have written off these metabolic abnormalities as due to the obesity that so often accompanies hypertension. In the obese person, glucose tolerance tends to be worse, serum triglycerides higher, and high density lipoprotein (HDL) cholesterol lower in comparison with the lean person matched for age, gender, and body fat distribution. In addition, obesity is a classic state of hyperinsulinemia and insulin resistance. Another element is that hypertension is strongly agerelated just as are a decline in glucose tolerance and an increase in the circulating levels of total cholesterol and triglycerides. Finally, treatment with some antihypertensive drugs, in particular thiazide diuretics and /3-blockers, has repeatedly been shown to have adverse effects on the metabolic profile of the hypertensive patient. These facts suggest a paradigm in which aging, overweight, and drug-related effects are responsible for bringing hypertension and glucose/lipid disorders together. In this view, the relation of the latter to the former is extrinsic; they are parallel branches of diverse origin, which environmental factors force to overlap. The young, lean, untreated hypertensive patients with definite (and otherwise unexplained) metabolic abnormalities clearly do not fit in this view. In such patients, significant insulin resistance has been shown to be present when compared with ageand weight-