EDUCATION AND OCCUPATION INFLUENCE RISK OF PARKINSON’S DISEASE

Individuals with a higher education level, including physicians, have an increased risk of developing Parkinson’s disease, while persons with some occupations presumed to involve high levels of physical activity have a reduced risk for the disease, according to Roberta Frigerio, MD, and colleagues. A report of their findings was published in the November 22, 2005, Neurology.

The researchers identified 202 patients residing in Olmsted County, Minnesota, who had an onset of Parkinson’s disease during a 20-year period. Each patient was individually matched by age and gender with a control who did not have Parkinson’s disease. Information about education and occupation was obtained independently by direct or proxy interview and by review of medical records. Records were available for 196 individuals (97%) in both case and control groups, and 149 cases (74%) and 129 controls (64%) were available for interviews.

Results indicated found that subjects with nine or more years of education had an increased risk of developing Parkinson’s disease compared with persons with a lower level of education, and there was a trend of increasing risk with increasing education. The reseachers also found that physicians "were at significantly increased risk using both medical records data and interview data." On the other hand, four occupational groups showed a significantly decreased risk for Parkinson’s disease—construction and extractive workers (eg, miners and oil well drillers), production workers (eg, machine operators and fabricators), metal workers, and engineers.

Dr. Frigerio and colleagues noted, "Our findings may be partly explained by a surveillance bias caused by increased recognition and earlier detection of Parkinson’s disease among educated subjects and physicians. Educated people and physicians may be more attentive to mild initial neurologic symptoms and may also have better access to specialistic care."

Furthermore, the investigators pointed out that "interpretation of the association of four occupational groups with reduced risk of Parkinson’s disease found in this study remains uncertain." They added that the findings might be due to chance, to a bias of nonparticipation in telephone interviews, or to confounding by lower education and resulting lower recognition of Parkinson’s disease.

Frigerio R, Elbaz A, Sanft KR, et al. Education and occupations preceding Parkinson disease. Neurology. 2005;65:1575-1583.

BIOMARKER LEVELS MAY PREDICT RECURRENT ISCHEMIC STROKE

Levels of soluble vascular cell adhesion molecule 1 (sVCAM-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), two biomarkers found in ischemic stroke patients, may provide prognostic information beyond traditional risk factors, according to a study in the January issue of Archives of Neurology.

Duncan J. Campbell, MD, PhD, and colleagues conducted a nested case-control study of participants in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled trial of a perindopril erbumine–based, blood pressure–lowering regimen that substantially reduced the risk of total stroke by 28% and ischemic stroke by 24%. Baseline levels of sVCAM-1, NT-proBNP, C-reactive protein, homocysteine, renin, and lipids, as well as lipoprotein particle concentration and size were measured in 252 patients who had had an ischemic stroke. Each case was matched with one to three controls, for a total of 544 controls without ischemic stroke.

The researchers found that patients "in the highest quarters for both sVCAM-1 and NT-proBNP levels had 3.6 times the risk of recurrent ischemic stroke compared with patients in the lowest quarters for both biological markers." In addition, "level of sVCAM-1 was similarly predictive of ischemic stroke in patients allocated to placebo and perindopril-based therapy."

Dr. Campbell and his colleagues also noted that "for most PROGRESS participants their increased risk of recurrent stroke was a consequence of their increased atherosclerotic plaque burden. Angiotensin II induces VCAM-1 expression in vasculature and may therefore contribute to the elevated sVCAM-1 levels in patients at increased risk of current ischemic stroke." However, "baseline plasma levels of C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size did not predict recurrent ischemic stroke risk."

The researchers pointed out several limitations to their study. "Our analyses were based on single baseline determinations that may not accurately reflect risk factor levels before enrollment or over the mean 3.9 years of follow-up," they stated. Additionally, "it is possible our grouping of ischemic strokes masked risk factors for specific ischemic stroke subtypes," and further, large studies are necessary to analyze this possibility.

"Characterization of the mechanisms of ischemic stroke pathogenesis associated with increased sVCAM-1 level may lead to development of therapies that provide benefits additional to those provided by [other] therapies," the investigators concluded.

Campbell DJ, Woodward M, Chalmers JP, et al. Soluble vascular cell adhesion molecule 1 and N-terminal pro-B-type natriuretic peptide in predicting ischemic stroke in patients with cerebrovascular disease. Arch Neurol. 2006;63:1-6.

INFLAMMATORY MARKERS MAY HELP PREDICT RISK OF ISCHEMIC STROKE

Levels of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) and C-reactive protein (CRP), in addition to traditional risk factors, may help identify middle-aged people at increased risk of ischemic stroke, according to results of a study published in the November 28, 2005, Archives of Internal Medicine.

Christie M. Ballantyne, MD, and colleagues assessed Lp-PLA₂ and CRP levels and their relation to ischemic stroke in 12,762 apparently healthy men and women ages 45 to 64 who participated in the Atherosclerosis Risk in Communities study. Lp-PLA₂ levels were assessed using a dual monoclonal antibody immunoassay standardized to recombinant Lp-PLA₂, while CRP levels were measured using an immunoturbidimetric CRP-Latex (II) high-sensitivity assay. Smoking status, alcohol consumption, BMI, waist-hip ratio, hypertension, and diabetes were also assessed.

Of 223 incident strokes, 194 were classified as ischemic strokes. Mean Lp-PLA₂ and CRP levels were higher in the 194 cases than in the 766 noncases, and low-density lipoprotein cholesterol levels were not significantly different between the two groups. Both Lp-PLA₂ and CRP levels were associated with ischemic stroke after adjustment for age, gender, and race. Participants with an Lp-PLA₂ level of 422 µg/L or higher had a 2.23-fold increased risk of ischemic stroke compared with those with an Lp-PLA₂ level lower than 310 µg/L. Participants with a CRP level higher than 3 mg/L had a 2.70-fold increased risk of ischemic stroke compared with those with a CRP level lower than 1 mg/L.

"Future studies should determine whether selective inhibition of Lp-PLA₂ or reduction and/ or inhibition of CRP reduces ischemic stroke and whether statins and/or fibrates are more effective for stroke prevention in patients with elevated levels of Lp-PLA₂," the researchers said.

However, in an accompanying editorial, Philip Greenland, MD, of Northwestern University, Chicago, and LTC Patrick G. O’Malley, MC, said, "It is unclear how useful CRP or Lp-PLA₂ level will be for improving risk prediction versus traditional risk factors alone. Simply showing statistical independence … is not adequate for demonstrating clinical utility for risk prediction."

Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Arch Intern Med. 2005;165:2479-2484.
Greenland P, O’Malley PG. When is a new prediction marker useful? A consideration of lipoprotein-associated phospholipase A2 and C-reactive protein for stroke risk. Arch Intern Med. 2005;165:2454-2456.

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