THE LANCET • Vol 354 • September 18, 1999 1029 hope in next year’s reports to contribute to the long-term goal of many in hypertension research. 1 Meanwhile, the placebo-controlled data from several long-term trials supports three of the four classes we studied, and the Captopril Prevention Project (CAPPP) trial provides reassurance for ACE inhibitor therapy on patients for whom they are the most effective class at lowering blood pressure. 2 Although most clinicians do not need reminding that the rationale for antihypertensive treatment is prevention of stroke, doctors should be able to measure and audit the goals for treatment. Therefore, to regard tangible targets as only “some ideal” seems ironic. Since the Hypertension Optimal Treatment (HOT) study banished fears about a J-shaped curve response to blood pressure reduction, there has been little doubt that blood pressure on treatment is the major predictor of outcome. 3 To see a patient with a stroke in sinus rhythm with a systolic blood pressure below 140 mm Hg is rare. Is there a contest, then, between the recommendations either to reduce systolic blood pressure to 140 mm Hg or to prescribe a thiazide diuretic (60% of hypertensive patients in England receive a thiazide, but only 6% meet the blood pressure target 4 )? Most previous comparisons of antihypertensives suggest that, even if the current outcome trials show significant differences in mean event rates between classes, they will not outweigh the differences in blood pressure reductions we saw in an individual between the classes. The value of the trials will probably be in reassuring us that the best antihypertensive treatment is indeed that which lowers blood pressure the most. We have speculated, further, that trials may confirm one extension of our AB/CD rule. 5 Angiotensin-suppressing and -blocking drugs (the AB pair) may be found more effective in preventing myocardial infarction, the principal risk in younger patients, whereas calcium channel-blockers and diuretics (the CD pair) may be preferable in older patients at higher risk of stroke. This difference may reflect their greater blood pressure reduction in high and low renin hypertension, respectively. Morris Brown Clinical Pharmacology Unit, University of Cambridge, Cambridge CB2 2QQ, UK (e-mail: m.j.brown@cai.cam.ac.uk) 1 Brown MJ, Castaigne A, De Leeuw PW, et al. Study population and treatment titration in the International Nifedipine GITS Study: intervention as a goal in hypertension treatment (INSIGHT). J Hypertens 1998; 16: 2113–16. 2 Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting- enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999; 353: 611–16. 3 Hansson L, Zanchetti A. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998; 351: 1755–62. 4 Colhoun HM, Dong W, Poulter NR. Blood pressure screening, management and control in England: results from the survey for England 1994. J Hypertens 1998; 16: 747–52. 5 Brown J, Brown MJ. CAPPP trial. Lancet 1999; 353: 1795–96. Surprisingly, patients with large vessel disease and without SVE had normal serum homocysteine concentration. The researchers concluded that homocysteine injures the small penetrating cerebral arteries and arterioles rather than larger arteries that supply the brain. Previous studies about the association between hyperhomocysteinaemia and cerebro- vascular disease have mainly focused on extracranial carotid artery stenosis and have always found higher homocysteine concentration in patients with large-vessel disease. 4 Prospective studies are needed to address whether hyperhomo- cysteinaemia is implicated in the development of SVE, but are difficult to do for this disease. Decreased incidence of SVE with the fortification of enriched grain products by folic acid might provide indirect evidence on the role of hyperhomocysteinaemia in the pathogenesis of SVE. * Didie r Ducloux, Je an-Marc Chalopin Department of Nephrology and Renal Transplantation, Saint Jacques Hospital, 25000 Besançon, France (e-mail: adjusy@ wanadoo.fr) 1 Faßender K, Mielke O, Bertsch T, Nafe B, Fröschen S, Hennerici M. Homocysteine in cerebral macroangiopathy and microangiopathy. L anc e t 1999; 353: 1 5 8 6 –8 7 . 2 Wollesen F, Brattström L, Refsum H, Ueland PM, Berglund L, Berne C. Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus. Kidney Int 1999; 55: 1 0 2 8 –3 5 . 3 Oshaug A, Bugge KH, Refsum H. Diet, and independent determinant for plasma total homocysteine. A cross sectional study of Norwegian workers on platforms in the north sea. Eur J Clin Nutr 1998; 52: 7 –1 1 . 4 Selhub J, Jacques PF, Bostom AG, et al. Association between plasma homocysteine concentrations and extracranial carotid- artery stenosis. N Engl J M ed 1995; 332: 2 8 6 –9 1 . Authors’ reply Sir—Didier Ducloux and Jean-Marc Chalopin argue that renal dysfunction could be responsible for raised homocysteine concentrations in patients with SVE, a cerebral microangiopathy that causes dementia. Age and hypertension, which are associated with this cerebral microangiopathy, can affect GFR— which is known to alter homocysteine blood concentrations. 1 , 2 Since Ducloux and Chalopin suggest that creatinine concentrations should be measured, we quantified this indicator of GFR in remaining fractions in 79 of 8 2 patients with SVE and in 132 of 144 patients with cerebral macroangiopathy. We saw no significant differences (Mann-Whitney Homocysteine in cerebral ma c roa ngiopa t hy and mic roa ngiopa t hy Sir—Klaus Faßbender and colleagues (May 8, p 1586) 1 report that patients with subcortical vascular encephalo- pathy (SVE) show significantly higher serum homocysteine concentration than patients with carotid artery disease and patients without any cerebrovascular disease. This result might be of interest in the understanding and prevention of SVE. However, we have some concerns about the results and conclusions drawn by the investigators. Logistic regression analysis showed that, beside hyperhomocysteinaemia, hypertension and age were also associated with SVE. Both long-term hypertension and age may affect renal function, which is a major determinant of homocysteine concentration. 2 Wollesen and colleagues 2 have shown that the age-related increase in serum homocysteine concentration is explained by declining glomerular filtration rate (GFR). Nevertheless, they do not mention serum creatinine concentration nor creatinine clearance. A difference in GFR between the three groups may be a serious bias in interpreting the study. Nor do they mention duration of disease. Serum homocysteine concen- trations are likely to have been measured a long time after the diagnosis of SVE, allowing changes in plasma homocysteine concentrations over time in response to different factors (ie, changes in diet). Many studies have shown the influence of diet on serum homocysteine co n cen t r a t io n . 3 Faßbender and colleagues do not assess whether SVE and progressive dementia could have modified diet.