The diagnosis and treatment of metabolic vitamin B12 deficiency, and B vitamins to lower homocysteine, can reduce the risk of stroke by approximately 30%. about 80%. With recent advances, we should be able to do even better. (aldosterone synthase); the latter includes mutations of ENac itself ( = 0.0001); diastolic control in 36% of UC vs. 67% of PhysRx ( = 0.003). Control was significantly worse in Kenya. When only the sites in Nigeria and South Africa were considered, systolic control was obtained in 15% of UC vs. 79% of PhysRx ( 0.0001), diastolic control in 45% vs. 71% ( = 0.04), and control of both in 15% vs. 67% ( = 0.0001). If only the Nigerian site (where patients were randomized to the two treatment strategies, = 0.0001), diastolic control in 45% vs. 75% ( = 0.11), and control of both systolic and diastolic pressure in 15% vs. 75% ( 0.0001) even though the renal function was worse at that site. Thus, it is clear that if diagnostic inertia can be overcome, there is a marked improvement in blood pressure control. The cost of the two blood assessments (around $50) is very low compared with the cost of high doses of the wrong medication and the cost of events such as stroke, renal failure, and heart failure from S5mt uncontrolled hypertension. This approach should be tested in a randomized trial in the US. Nutrition Mediterranean diet Diet is far more important than most physicians (and the public) suppose. In the Lyon Diet Heart Study 21, there was a greater than 60% reduction of stroke and myocardial infarction over 4 years in secondary prevention. This was approximately twice the effect of simvastatin in the contemporaneous Scandinavian Simvastatin Survival Study 22 (a 40% reduction of recurrent myocardial infarction in 6 years). In the US, the worst of the lifestyle and risk factor issues is diet: only 0.1% of Americans consume a healthy diet, and only 8.3% consume even a moderately healthy diet 3. Adherence to a Mediterranean diet reduces the risk of ischemic stroke 23, adherence to a healthy diet and other way of life factors reduced myocardial infarction in Swedish men by 80% 24, and a healthy diet and other way of life factors reduced stroke in Swedish women by 62% 25. In 2013, it was already clear that, compared to a low-fat diet, a Mediterranean diet significantly reduced stroke in primary prevention: there was a 47% reduction of stroke in the Mediterranean arm of the study fortified with mixed nuts 26. Since then, it has been reported that this Mediterranean diet improved the metabolic syndrome 27 and reduced age-related cognitive decline 28. B vitamin therapy to lower homocysteine In 2004, the Vitamin Intervention in Stroke (VISP) trial 29 reported no benefit of folic acid 2.5 mg, pyridoxine 25mg, and cyanocobalamin 400 g daily compared with low-dose vitamins. In 2006, when the Norwegian Vitamin Trial (NORVIT) 30 and the Heart Outcomes Prevention Evaluation (HOPE-2) trial 31 were published, the cant was homocysteine is usually dead. Loscalzo hypothesized 32 that harm from unmetabolized folic acid may have accounted for the null results. However, in NORVIT, there HG-14-10-04 was harm from B vitamins in the arm of the study that included cyanocobalamin, and in HOPE-2 there was actually a 23% reduction of stroke with B vitamins. In the French SU.FOL.OM3 trial 33, there was also a 43% reduction of stroke in a study in which renal function HG-14-10-04 was better than in earlier studies: mean serum creatinine in SU.FOL.OM3 was 78 mmol/L compared with 99.9 mmol/L in VISP, 91 mmol/L in NORVIT, and 88.4 mmol/L in HOPE-2. Some meta-analyses also indicated a reduction of stroke with B vitamins HG-14-10-04 34, 35. Importantly, the form of vitamin B12 used in all of these studies was cyanocobalamin, a form that contains cyanide, which must be decyanated to become active. Cyanide is usually converted to thiocyanate before renal elimination occurs, consuming hydrogen sulfide (H 2S), a gasotransmitter 36 that is an endothelium-derived relaxing factor, in the process, and thiocyanate is usually a powerful oxidant, accelerating the oxidation of LDL cholesterol (LDL-C) 37. It accumulates in renal.