Homocysteine – does it predict heart disease?

Yesterday I got a press release headed ‘High blood homocysteine levels are not linked with coronary heart disease’ based on a meta-analysis, a study of studies, published in the Public Library of Science Medicine journal.

The authors, headed by Robert Clarke from the University of Oxford, who has been consistently dismissive of the homocysteine heart connection, looked at the difference between coronary heart disease risk between those whose inherit a variation of a gene that makes an enzyme that lowers homocysteine. Since having this potential genetic disadvantage, called the TT genotype, generally raises homocysteine levels by about 18 per cent, the authors were testing the theory that, consequently those with the TT genotype should have a significantly raised risk for heart disease. It should be pointed out, however, that most of the people studied had not had their homocysteine levels measured, and of those that did, most were not outside of the normal range.

There’s a lot of hoohaa in the paper about ‘eliminating confounding variables and publication bias’ to try and explain away the fact, also stated in the paper, that analysis of published studies actually show that those with the TT genotype do have an increased risk of CHD, ranging from 12 to 18%. Unlike the headline of the press release ‘high homocysteine levels are not linked to CHD’ an editorial in the journal summarises ‘ these findings indicate that circulating homocysteine levels within the normal range are not causally related to CHD risk.” Who inserted this word ‘high’ in the press release title, ambiguous in that one might think that the people studies did have an above normal level of homocysteine? Here’s a corollary. Imagine getting a press release stating ‘high cholesterol not linked to heart disease’, relating to a paper showing that people with cholesterol levels in the normal range, but with a genotype that is expected to slightly raise cholesterol, did not have a greater risk of heart disease.

The point I make consistently is that there is going to be a threshold of homocysteine, and of cholesterol for that matter, above which risk for certain diseases occur. For example, for Alzheimer’s in appears to be 10mcmol/l. For cardiovascular disease maybe it is higher. Studies using high dose B vitamins in patients with homocysteine above 15mcmol/l have consistently shown reduction in risk. In relation to strokes a study, published in 2001, showed that a raised homocysteine level is a better predictor of cardiovascular problems than a stroke victim’s age (each additional year adds only a 6 per cent risk), blood pressure, cholesterol level or whether or not they smoked. It involved 1,158 women and 789 men aged 60 years or older who had already taken part in studies investigating homocysteine levels as a predictor for stroke.

After seven years, those who had had a homocysteine score above 14 mcmol/l had an 82 per cent increased risk of total stroke, compared to those with less than 9.2. If your level is slightly raised (5 points higher than normal) you’ll increase your risk of a heart attack by 42 per cent, of deep vein thrombosis by 60 per cent and of a stroke by 65 per cent, according to a meta-analysis of 92 studies in the British Medical Journal. ‘These results provide strong evidence that the association between homocysteine and cardiovascular disease is causal,’ said the lead author David Wald, Clinical Research Fellow in Cardiology at the Wolfson Institute of Preventive Medicine at Barts in London. In another study published in the British Medical Journal, the best predictor by far was homocysteine: a level above 13mcmol/l predicted no fewer than two-thirds of all deaths five years on.

Another finds that having a homocysteine above 15mcmol/l more than doubles your risk or both cardiovascular disease, having or dying from a cardiovascular event. Wald, who has criticised this recent analysis, also argues that the “appropriate analysis” to perform would be to combine the published data from the 86 studies and the new data used in this study from the 19 unpublished studies, “not present them separately and then ignore the published ones.” He says “A combined analysis, not presented by the authors, supports a causal association that is consistent with previously published estimates, with about a 10% increased risk of heart disease rather than the 15% reported.” Don’t throw the baby out with the bathwater. Homocysteine is still a predictor of heart disease, and important to lower if it is high. In this context ‘high’ might be somewhere between 13 and 15mcmol/l. With an average homocysteine level in the UK of around 11mcmol/l that’s a lot of people at risk who could be helped by supplementing much higher than RDA amounts of B6, B12 and folic acid. (To test and lower your homocysteine with a nutritional strategy read my Special Report.

It is a shame that these authors don’t make this point in their fervour to dismiss homocysteine as a potential contributor to heart disease risk. This kind of biased reporting discourages doctors from screening for this important and neglected risk factor.