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Rational Medical Therapy Is the Key to Effective Cardiovascular Disease Prevention.

In an era in which medicine personalized on the basis of genotyping is being proposed, it is timely to recognize that existing therapies could be markedly improved if they were on the basis of more effective application of principles on the basis of available phenotyping. Blood pressure control, which is poor on a worldwide basis, is a major opportunity to reduce cardiovascular risk. There are many genetic variants that have a small effect on blood pressure, but specific therapies are not available for most of them. Individualized therapy for hypertension using plasma renin and aldosterone to identify the physiological drivers of hypertension might markedly improve blood pressure control. For patients with a high renin/high aldosterone phenotype, angiotensin receptor blockers are indicated. For those with a high aldosterone/low renin (primary aldosteronism) phenotype, aldosterone antagonists are best; for those with low renin/low aldosterone (a Liddle phenotype), amiloride is best. Effective antiplatelet therapy and anticoagulation, particularly with the new oral anticoagulants, can markedly reduce the risk of stroke. Metabolic B12 deficiency is very common, usually missed, and easily treated; B vitamins to lower homocysteine levels might be able to reduce the risk of stroke, particularly among elderly patients with atrial fibrillation. A particularly useful phenotype is carotid plaque burden. In high-risk patients, intensive lipid-lowering therapy aimed to prevent progression of carotid plaque can reduce the risk of stroke or myocardial infarction by > 80%. Available therapies, used more rationally on the basis of clinical pharmacology and phenotyping of our patients, could have a bigger effect than genome-based personalized medicine.

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