Review Course: Continued Laragh’s Lessons in Pathophysiology and Clinical Pearls for Treating Hypertension Introduction to Lessons X to XII

Last month, we presented the evidence implicating plasma renin-angiotensin excesses (ie, excess plasma renin activity levels) as the cause of malignant hypertension and of its cardiac, cerebral, and renal vessel damage, which lead rapidly to fatal heart attack or stroke, or heart or kidney failure. We also showed that milder but inappropriate excesses of plasma renin angiotensin directly sustain part or all of the hypertension of patients with medium and high renin essential hypertension but plays little or no role in causation of the other 30% of patients who have low renin essential hypertension, in whom a sodium volume excess instead sustains the hypertension. Accordingly, this hypertension is correctable instead by sodium depletion and is not responsive to anti-renin system drugs. This month in Lessons 10, 11 and 12 we present clinical and experimental evidence indicating that the milder excesses of plasma renin, which cause and sustain most essential hypertension, are also highly associated with later more gradual occurrences of heart attacks and strokes, not observed in patients with low renin hypertension. These differences occur even though the low-renin patients are older by some 12 years and had even higher blood pressures. These findings implicating plasma renin levels in subsequent vascular injury are buttressed by our experiments in genetic hypertensive animal models and by many large clinical trials in the worlds of cardiology and nephrology, in all of which progression of coronary or of diabetic or nondiabetic small vessel renal diseases are uniquely arrested by treatment with specific anti-renin system drugs.