Inflammation-Sensitive Proteins: Another Ingredient in Stroke?
When Swedish researchers monitored >6000 men for nearly 20 years after measuring levels of cholesterol and 5 inflammation-sensitive plasma proteins (fibrinogen, Α1-antitrypsin, haptoglovin, ceruloplasmin, and orosomucoid), they found that high levels of these compounds were associated with hypercholesterolemia, increasing the risk of cardiovascular diseases. A report of their work appears in this week’s issue of Circulation (Circulation. 2002;105:2632–2637).
Defining high levels of inflammation-sensitive plasma proteins as levels of at least 2 in the upper quartile, the researchers, led by Gunnar Engström, MD, PhD, of the University of Malmo in Sweden, found that hypercholesterolemia was associated with an increased incidence of ischemic stroke, cardiac events, and reduced incidence of intracerebral hemorrhage in these groups. However, they also discovered that levels of inflammation-sensitive proteins changed this association. Men with hypercholesterolemia and high levels of inflammation-sensitive proteins had a significantly higher risk of ischemic stroke and cardiovascular mortality and events than did men with normal levels of cholesterol and inflammation-sensitive proteins. When the levels of inflammation-sensitive proteins were not high, hypercholesterolemia was associated with a moderately high risk of cardiovascular death and events, but not with ischemic stroke. They concluded that hypercholesterolemia is associated with high levels of the inflammation-sensitive proteins, which increase cholesterol-related incidence of ischemic stroke and heart attack.
In an accompanying editorial (Circulation. 2002;105:2583–2585), Paul M. Ridker, MD, MPH, of The Brigham and Women’s Hospital and Harvard Medical School in Boston, noted, “A central paradox of the cholesterol hypothesis is that long-term treatment with statins reduces the risk of stroke, yet LDL (low-density lipoprotein) cholesterol is not a strong risk factor for stroke.” This finding has encouraged research into the effects of statins other than lipid lowering, as well as research of inflammatory markers that might be associated with stroke, he said.
He noted that in this paper, the Swedish authors suggested that their observational data might support the hypothesis that inflammation may play a larger role in stroke than in heart attack and other cardiovascular disease. Finding a way to predict patient risk of heart disease and stroke is an increasingly important problem, Dr Ridker notes, because of the mortality and morbidity associated with the 1.5 million myocardial infarctions and 700 000 strokes that will occur in the United States alone this year.
“If an inexpensive method to detect vascular risk can improve physician compliance with established prevention guidelines, as well as increase patient motivation for diet, exercise, blood pressure control, and smoking cessation, then the goal of preventing atherothrombotic disease will be one step closer,” Dr Ridker concluded.
Your Mother Was Right
Eating at least 5 servings daily of fruit and vegetables can reduce your risk of heart disease and cancer, according to British researchers in the May 28, 2002, online edition of The Lancet (Available at: http://image.thelancet.com/extras/01art9006web.pdf).
Andrew Neal, MD, and colleagues from the University of Oxford, found that a 6-month intervention to increase the fruit and vegetable consumption among 345 people from the primary care health center in the United Kingdom decreased blood pressure and increased concentrations of Α-carotene, β-carotene, lutein, β-cryptoxanthin, and ascorbic acid. Levels in a control group of the same size remained the same.
Dr Neal concluded, “The falls in blood pressure in our study would be expected to produce small clinical effects, but would substantially reduce cardiovascular disease at the population level. A reduction of 2 mm Hg in diastolic blood pressure results in a decrease of about 17% in incidence of high blood pressure, 6% in the risk of coronary artery disease, and 15% in the risk of stroke and transient ischemic attack.”
Another Bad Mark Against Homocysteine
Two studies in the May 28, 2002, issue of Neurology (Neurology. 2002;58:1471–1475; Neurology. 2002;58:1539–1541), the journal of the American Academy of Neurology, link high levels of homocysteine to brain atrophy and vascular disease—2 conditions known to be related to dementia of all kinds, including Alzheimer’s disease.
In a study led by Perminder Sachdev, MD, PhD, of the University of New South Wales in Sydney, Australia, researchers tested the homocysteine levels of 36 healthy, elderly people. They then measured the amount of brain atrophy or loss of volume with the use of a magnetic resonance imaging scan. Those who had the greatest amount of brain atrophy were twice as likely to have high homocysteine levels as those whose brains had less atrophy, they reported.
Researchers, led by Joshua W. Miller, PhD, of the University of California at Davis, measured homocysteine levels in 37 healthy patients as well as in 43 patients with Alzheimer’s disease. Those with high levels of the amino acid were 10 times more likely to have vascular disease, Dr Miller said.
“The study didn’t find a relationship between high homocysteine levels and Alzheimer’s disease per se—as has been reported previously—but rather suggests that in studies that did demonstrate this association, the effect may be mediated by vascular disease,” he said in a released statement. He and his colleagues found that patients with Alzheimer’s were much more likely to have low levels of the vitamin B6 than were healthy people.