Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
PLoS Med. 2019 Nov 12;16(11):e1002933. doi: 10.1371/journal.pmed.1002933. eCollection 2019 Nov.
Variation in blood pressure may relate to dementia risk via autonomic disturbance or hemodynamic mechanisms, but the long-term associations are unclear. We aimed to determine whether blood pressure variation over a period of years, considering both magnitude and direction, is associated with the risk of dementia.
In a prospective cohort study ongoing since 1989 in the Netherlands, 5,273 dementia-free participants (58.1% women; mean [SD] age, 67.6 [8.0] years) were included. As of 2016, 1,059 dementia cases occurred during a median follow-up of 14.6 years. Absolute variation in systolic blood pressure (SBP) was assessed as the absolute difference in SBP divided by the mean over two sequential visits every 4.2 (median) years, with the first quantile set as the reference level. The direction was the rise or fall in SBP, with the third quantile set as the reference level. We estimated the risk of dementia in relation to SBP variation measured at different time windows (i.e., at least 0, 5, 10, and 15 years) prior to dementia diagnosis, with adjustments for age, sex, education, apolipoprotein E (APOE) genotype, vascular risk factors, and history of cardiovascular disease. We repeated the above analysis for variation in diastolic blood pressure (DBP). A large SBP variation was associated with an increased dementia risk, which became more pronounced with longer intervals between the assessment of SBP variation and the diagnosis of dementia. The hazard ratio (HR) associated with large variation (the highest quintile) increased from 1.08 (95% confidence interval [CI] 0.88-1.34, P = 0.337) for risk within 5 years of SBP variation measurement to 3.13 (95% CI 2.05-4.77; P < 0.001) for risk after at least 15 years since the measurement of SBP variation. The increased long-term risk was associated with both large rises (HR for the highest quintile, 3.31 [95% CI 2.11-5.18], P < 0.001) and large falls in SBP (HR for the lowest quintile, 2.20 [95% CI 1.33-3.63], P = 0.002), whereas the higher short-term risk was only associated with large falls in SBP (HR, 1.21 [95% CI 1.00-1.48], P = 0.017). Similar findings were observed for variation in DBP. Despite our assessment of major confounders, potential residual confounding is possible, and the findings on blood pressure variability over periods of years may not be generalizable to variability over periods of days and other shorter periods.
Results of this study showed that a large blood pressure variation over a period of years was associated with an increased long-term risk of dementia. The association between blood pressure variation and dementia appears most pronounced when this variation occurred long before the diagnosis. An elevated long-term risk of dementia was observed with both a large rise and fall in blood pressure.
血压变化可能通过自主神经紊乱或血流动力学机制与痴呆风险相关，但长期关联尚不清楚。我们旨在确定多年来血压变化的幅度和方向是否与痴呆风险相关。
在一项自 1989 年以来在荷兰进行的前瞻性队列研究中，纳入了 5273 名无痴呆症参与者（58.1%为女性；平均[SD]年龄为 67.6[8.0]岁）。截至 2016 年，在中位随访 14.6 年后，发生了 1059 例痴呆病例。收缩压（SBP）的绝对变化通过两次连续就诊时 SBP 的绝对差值除以两次就诊的平均 SBP 来评估，每 4.2（中位数）年一次，第一分位数设为参考水平。方向是 SBP 的上升或下降，第三分位数设为参考水平。我们根据年龄、性别、教育程度、载脂蛋白 E（APOE）基因型、血管危险因素和心血管疾病史，估计了在痴呆诊断前不同时间窗口（即至少 0、5、10 和 15 年）测量的 SBP 变化与痴呆风险之间的关系。我们重复了上述舒张压（DBP）变化的分析。较大的 SBP 变化与痴呆风险增加相关，且随着 SBP 变化评估与痴呆诊断之间的间隔时间延长，风险更为显著。与 SBP 变化测量后 5 年内的风险相比，与大变化（最高五分位组）相关的风险比（HR）从 1.08（95%置信区间[CI]0.88-1.34，P=0.337）增加到 15 年以上的风险增加到 3.13（95%CI2.05-4.77；P<0.001）。长期风险增加与 SBP 较大升高（最高五分位组的 HR，3.31[95%CI2.11-5.18]，P<0.001）和较大下降（最低五分位组的 HR，2.20[95%CI1.33-3.63]，P=0.002）相关，而短期风险增加仅与 SBP 较大下降相关（HR，1.21[95%CI1.00-1.48]，P=0.017）。DBP 变化也有类似的发现。尽管我们评估了主要混杂因素，但仍可能存在潜在的混杂因素，且多年期间血压变化的结果可能无法推广到数天或其他较短时间内的变化。
本研究结果表明，多年来血压变化幅度较大与痴呆的长期风险增加相关。当这种变化发生在痴呆诊断很久以前时，血压变化与痴呆之间的关联最为明显。血压的大幅升高和下降都与痴呆的长期风险升高有关。
