Stroke Prevention: A Lifetime of Lessons

Abstract

In 44 years of practicing stroke prevention, I have learned many lessons; in this article, I hope to impart some of them. Three areas of my research are discussed. Controlling resistant hypertension is markedly improved by physiologically individualized therapy based on renin/aldosterone phenotyping; this is particularly important in black patients. Measurement of carotid plaque burden strongly predicts cardiovascular risk and is useful for genetic research and for a process called treating arteries instead of risk factors. Doing so in high-risk patients with asymptomatic carotid stenosis was associated with a >80% reduction in the 2-year risk of stroke and myocardial infarction. It also permitted the identification of extremes of atherosclerosis that are useful for studying both the genetics and the biology of atherosclerosis. Patients with very high plaque burden despite low levels of risk factors have an unexplained phenotype; those with little or no plaque despite high levels of risk factors are protected. Patients with unexplained atherosclerosis have higher plasma levels of toxic metabolites produced by the intestinal microbiome largely from egg yolk, red meat, and protein, and those metabolites are renally excreted. This has important dietary implications for stroke prevention. Lowering of plasma total homocysteine with B vitamins significantly reduces the risk of stroke. That was not apparent in early studies because harm from cyanocobalamin among participants with renal failure obscured the benefit among those with good renal function. We should be using B vitamins to prevent stroke but should use methylcobalamin or oxocobalamin instead of cyanocobalamin.

Keywords: aldosterone; atherosclerosis; homocysteine; hypertension; renin.