Fujiyoshi Akira, Jacobs David R, Fitzpatrick Annette L, Alonso Alvaro, Duprez Daniel A, Sharrett A Richey, Seeman Teresa, Blaha Michael J, Luchsinger José A, Rapp Stephen R
From the Department of Public Health, Shiga University of Medical Science, Japan (A.F.); Division of Epidemiology and Community Health, School of Public Health (A.F., D.R.J.) and Cardiovascular Division, Department of Medicine (D.A.D.), University of Minnesota, Minneapolis; Departments of Family Medicine, Epidemiology, and Global Health, University of Washington, Seattle (A.L.F.); Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (A.A.); Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD (A.R.S.); Departments of Medicine and Epidemiology, University of California, Los Angeles (T.S.); The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD (M.J.B.); Departments of Medicine and Epidemiology, Columbia University Medical Center, New York, NY (J.A.L.); and Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC (S.R.R.).
Circ Cardiovasc Imaging. 2017 May;10(5). doi: 10.1161/CIRCIMAGING.116.005349.
Studies suggest a link between vascular injuries and dementia. Only a few studies, however, examined a longitudinal relation of subclinical vascular disease with dementia. We tested whether baseline coronary artery calcium (CAC), a biomarker of subclinical vascular disease, is associated with incident dementia independent of vascular risk factors and APOE-ε4 genotype in a community-based sample.
We analyzed 6293 participants of MESA (Multi-Ethnic Study of Atherosclerosis), aged 45 to 84 years at baseline (2000-2002), initially free of cardiovascular disease and noticeable cognitive deficit. Dementia cases were identified using hospital and death certificate International Statistical Classification of Diseases and Related Health Problems codes. Cox models were used to obtain hazard ratios according to CAC category, or per 1 SD log2[CAC+1], adjusted for vascular risk factor, APOE-ε4, with or without exclusion of interim stroke or cardiovascular disease. We observed 271 dementia cases in a median follow-up of 12.2 years. Baseline CAC had a graded positive association with dementia risk. Compared with no CAC, CAC score of 1 to 400, 401 to 1000, and ≥1001 had increased risk of dementia by 23%, 35%, and 71%, respectively, (=0.026) after adjustment. 1 SD higher log2[CAC+1] was associated with 24% (95% confidence interval, 8%-41%; =0.002) increase in dementia risk. Although the association was partially explained by interim stroke/cardiovascular disease, it remained significant even after excluding the interim events, or regardless of baseline age.
Higher baseline CAC was significantly associated with increased risk of dementia independent of vascular risk factor, APOE-ε4, and incident stroke. This is consistent with a hypothesis that vascular injuries play a role in the development of dementia.
研究表明血管损伤与痴呆之间存在联系。然而，仅有少数研究探讨了亚临床血管疾病与痴呆的纵向关系。我们在一个基于社区的样本中测试了基线冠状动脉钙化（CAC）这一亚临床血管疾病的生物标志物，是否独立于血管危险因素和APOE-ε4基因型与痴呆的发生相关。
我们分析了动脉粥样硬化多民族研究（MESA）的6293名参与者，基线时（2000 - 2002年）年龄在45至84岁，最初无心血管疾病且无明显认知缺陷。使用医院和死亡证明的国际疾病分类及相关健康问题编码来确定痴呆病例。采用Cox模型根据CAC类别或每1个标准差的log2[CAC + 1]获得风险比，并对血管危险因素、APOE-ε4进行调整，包括或不包括排除中期中风或心血管疾病的情况。在中位随访12.2年期间，我们观察到271例痴呆病例。基线CAC与痴呆风险呈分级正相关。调整后，与无CAC相比，CAC评分为1至400、401至1000以及≥1001时，痴呆风险分别增加23%、35%和71%（P = 0.026）。log2[CAC + 1]每增加1个标准差，痴呆风险增加24%（95%置信区间，8% - 41%；P = 0.002）。尽管这种关联部分可由中期中风/心血管疾病解释，但即使排除中期事件或不考虑基线年龄，其仍具有显著性。
较高的基线CAC与痴呆风险增加显著相关，独立于血管危险因素、APOE-ε4和中风事件。这与血管损伤在痴呆发生中起作用的假设一致。
