Relationship between insulin resistance and nonmodulating hypertension - Linkage of metabolic abnormalities and cardiovascular risk

Insulin resistance is a feature common to patients with diabetes and to som e with hypertension. It is assumed that this feature confers the increased metabolic risk in hypertension. However, the state of the renin-angiotensin system might contribute to cardiovascular risk, although there is no clear mechanistic explanation. Our recent observation that insulin levels are in creased in a specific subset of patients with normal/high-renin hypertensio n, the nonmodulators, provided the background for the current hypothesis: t o ascertain whether abnormalities in lipid and carbohydrate metabolism are observed in the same patients in whom alterations in sodium transport, sodi um homeostasis, and the renin-aniotensin system response have been identifi ed. Exploration of a family history of cardiovascular risk was a secondary goal. Insulin sensitivity (assessed by a 75-g oral glucose load), lipid lev els, and two defects in the renin-angiotensin system were assessed in 62 hy pertensive and 14 normotensive subjects placed on a high (210 mmol/l) and a low (10 mmol/l) sodium intake for 2 weeks, to classify them as low-renin, nonmodulator, or modulating hypertensive subjects. Only in nonmodulators we re the following cardiovascular risk factors significantly increased: fasti ng insulin (P < 0.01); increment in post-glucose load insulin (P < 0.01); t otal, LDL, and VLDL cholesterol and triglyceride levels (P < 0.05); and ery throcyte Na+/Li+ countertransport activity (P < 0.001). Both nonmodulators and low-renin hypertensive subjects had a significantly (P < 0.01) increase d frequency of a family history of hypertension by questionnaire compared w ith subjects with intact modulation. However, only nonmodulators had a sign ificantly (P < 0.02) higher frequency of a family history of myocardial inf arction. Thus, there is a clustering of metabolic abnormalities in a discre te subset of the essential hypertensive population with a specific dysregul ation of the renin-angiotensin system-nonmodulation. The absence of this cl uster in low-renin hypertensive subjects may explain their relatively dimin ished cardiovascular risk. Its presence in nonmodulators likely contributes to the increased cardiovascular risk observed in normal/high-renin hyperte nsion.