Certain inflammation markers seem to be related to increased risk of ischemic heart disease (angina pectoris and heart attack), according to three studies conducted by Cand.med. Inga Thorsen Vengen at the Department of Laboratory Medicine, Children’s and Women’s Health, NTNU.
The motivation behind the research has been to identify more potential risk factors for heart disease, especially in light of the fact that many of those admitted with acute heart attack (myocardial infarction) do not feature the traditional risk factors such as smoking, high blood pressure, high cholesterol, overweight, etc.
It is known that the inflammation defense is activated in atherosclerosis, and the three studies aim to increase the understanding of the disease processes, and thereby find new risk markers.
Diabetes increases risk
The first two studies are based on diabetics, which is a high-risk group for ischemic heart disease, amongst other things, because high blood sugar triggers the inflammation defense. Vengen used data from the HUNT 1 study, where 200 individuals with newly discovered diabetes were followed over a 20-year period. Blood test results were linked to cause of death ischemic heart disease.
Four inflammation makers were measured: C-reactive protein (CRP), neopterin, lactoferrin, and myeloperoxidase (MPO).
Vengen found that diabetics with high levels of neopterin and CRP had increased risk of dying of ischemic heart disease independently of traditional risk factors.
Neopterin is a marker that appears to have a clear link to bursting plaque and the restriction of blood vessels (see fact box for Atherosclerosis). Neopterin seemed to be a more specific marker than CRP, which reflects a more general state of inflammation in the body (and is therefore probably not as closely linked to atherosclerosis).
In the second study form the same material, researchers looked into markers from neutrophil granulocytes, which are central cells in plaque and which do not function optimally in people with diabetes. The results show that those with high lactoferrin levels had an increased risk of dying of ischemic heart disease. MPO did not have the same effect.
In the third study Vengen looked at whether genetic changes leading to variations in the inflammation defense could be related to the risk of atherosclerosis.
Variations in the gene controlling the protein mannose-binding lectin (MBL) were studied, and those with a genetic variation leading to a lack of MBL had doubled risk of heart attack.
This study is based on results from HUNT 2, where the 370 youngest (aged 29-62) admitted for heart attack were matched against 370 controls.
Vengen says it is still a long way to go before these results can be used clinically:
“There’s a big difference between finding associations – things occurring simultaneously – with heart attack, and finding a cause. But what we find could lead to new hypotheses about causes.”
The results of the study involving the diabetics have already lead to researchers starting a larger study with all diabetics in HUNT 2 to do some of the same analyses, but also to see if new findings emerge. With a larger study, the results may also lead to larger generalizations.
The thesis “Inflammation and risk atherosclerosis – Risk associations in the HUNT surveys” will be defended at 12.15 on 15. June 2012. The trial lecture “Cardiovascular disease prevention in diabetes mellitus” will be held at 10.15 in LA21.
Atherosclerosis and ischemic heart disease
Atherosclerosis is an inflammation process in the blood vessel wall where lipids and cholesterol gather, triggering the inflammation defense. The defense is not able to remove the cause, however, and there is a constant activation of the inflammation system which leads to a vicious circle where more lipids and inflammatory cells are attracted, which again leads to plaque. When the blood vessel becomes too restricted and/or the plaque bursts, a clot develops which can lead to heart attack (myocardial infarction).
Ischemic heart disease is caused by atherosclerosis in the blood vessels leading to the heart, as seen in heart attack and angina pectoris (heart cramps).
- Mannose-binding lectin deficiency is associated with myocardial infarction: the HUNT2 Study in Norway. Vengen IT et.al. (Submitted)
- Lactoferrin is a novel predictor of fatal ischemic heart disease in diabetes mellitus type 2: Long-term follow-up of the HUNT 1 study. Vengen IT et.al. Atherosclerosis 2010.
- Neopterin predicts the risk for fatal ischemic heart disease in type 2 diabetes mellitus. Long-term follow-up of the HUNT 1 study. Vengen IT et. al. Atherosclerosis 2009.
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