Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
Stroke. 2010 Apr;41(4):607-12. doi: 10.1161/STROKEAHA.109.558742. Epub 2010 Feb 11.
Natural immunoglobulin M antibodies specific for phosphorylcholine (anti-PC) have been implicated in atherosclerosis. We have shown previously that high levels of anti-PC predict a slower progression of atherosclerosis in humans and that low levels of anti-PC are associated with higher risk for cardiovascular disease. Here we determine the association between anti-PC and the incidence of stroke.
Using a nested case control study design, we examined 227 incident cases (125 men and 102 women) of first-time stroke and 455 age- and sex-matched controls identified during a 13-year time period (1985 to 1999) within the population-based cohorts of the Västerbotten Intervention Project (VIP) and the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) project in Northern Sweden. Odds ratios of stroke with 95% CIs with adjustments for age, gender, smoking, serum cholesterol, diabetes, body mass index, and blood pressure were determined. Anti-PC levels were measured using ELISA.
A significant association between low levels of anti-PC at baseline and incident stroke was seen for the whole group of anti-PC levels below the 30th percentile (multivariately adjusted odds ratio, 1.62; CI, 1.11 to 2.35). Analyses of gender-specific associations indicated fairly strong associations for females, especially at the lowest 30th percentile (multivariately adjusted odds ratio, 2.65; CI, 1.41 to 4.95). No associations were noted for men.
Low anti-PC is a novel independent risk marker for development of stroke. Measurements of anti-PC could be used to identify immunodeficient subjects at an increased risk for stroke. The possibility that such subjects might be targets for novel modes of treatment such as immunotherapies deserves further investigation.
针对磷酸胆碱的天然免疫球蛋白 M 抗体(抗 PC)已被证实与动脉粥样硬化有关。我们之前的研究表明,高水平的抗 PC 可预测人类动脉粥样硬化的进展速度较慢,而低水平的抗 PC 与心血管疾病风险增加相关。在此,我们确定抗 PC 与中风发病之间的关联。
采用巢式病例对照研究设计,我们检测了在 13 年时间内(1985 年至 1999 年)于基于人群的维斯特博滕干预研究(VIP)和世界卫生组织监测心血管疾病趋势和决定因素(WHO MONICA)项目中发现的 227 例首发中风病例(125 例男性和 102 例女性)和 455 例年龄和性别匹配的对照者。使用调整年龄、性别、吸烟、血清胆固醇、糖尿病、体重指数和血压后,确定具有 95%置信区间的中风比值比(OR)。使用 ELISA 法测定抗 PC 水平。
在整个抗 PC 水平低于第 30 百分位数的组中,基线时低水平的抗 PC 与中风发病显著相关(多变量校正 OR,1.62;95%CI,1.11 至 2.35)。性别特异性关联分析表明,女性关联较强,尤其是在最低的第 30 百分位数(多变量校正 OR,2.65;95%CI,1.41 至 4.95)。未观察到男性的关联。
低抗 PC 是中风发病的新的独立危险因素。抗 PC 的测量可用于识别免疫功能低下的中风高危人群。这些人群是否可能成为新型治疗模式(如免疫疗法)的治疗靶点,值得进一步研究。