■关于血压(BP)和抗高血压治疗对脑小血管疾病的影响,先前的研究得出了相互矛盾的结果。这里,我们进行了一项孟德尔随机研究,以研究血压和降压药物对脑小血管疾病的影响.
■我们从全基因组关联研究(N=757601)中提取了收缩压和舒张压的单核苷酸多态性,并筛选了与钙通道阻滞剂相关的单核苷酸多态性,噻嗪类,血管紧张素转换酶抑制剂,血管紧张素受体阻滞剂,和来自公共资源的β受体阻滞剂作为工具变量。然后,我们选择了白质高强度的全基因组关联研究(WMH;N=18381),脑微出血(3556例,22306控件),白质血管周围间隙(9317例,29281个控件),基底神经节血管周围间隙(BGPVS;8950例,29953个控件),海马血管周围间隙(HIPPVS;9163例,29708控件),和腔隙性中风(6030例,248929个对照)作为结果数据集。随后,我们进行了2个样本孟德尔随机化分析.
■我们发现收缩压升高会显著增加BGPVS的风险(比值比[OR],1.05[95%CI,1.04-1.07];P=1.72×10-12),HIPPVS(或,1.04[95%CI,1.02-1.05];P=2.71×10-7),和腔隙中风(或,1.41[95%CI,1.30-1.54];P=4.97×10-15)。有暗示性证据表明收缩压升高与WMH体积增加相关(β=0.061[95%CI,0.018-0.105];P=5.58×10-3),并导致脑微出血风险增加(OR,1.16[95%CI,1.04-1.29];P=7.17×10-3)。舒张压升高与WMH体积升高显著相关(β=0.087[95%CI,0.049-0.124];P=5.23×10-6),并显著增加BGPVS的风险(OR,1.05[95%CI,1.04-1.06];P=1.20×10-16),HIPPVS(或,1.03[95%CI,1.02-1.04];P=2.96×10-6),和腔隙中风(或,1.31[95%CI,1.21-1.41];P=2.67×10-12)。使用钙通道阻滞剂降低血压与降低WMH体积显着相关(β=-0.287[95%CI,-0.408至-0.165];P=4.05×10-6),并显着降低BGPVS的风险(OR,0.85[95%CI,0.81-0.89];P=8.41×10-19)和HIPPVS(OR,0.88[95%CI,0.85-0.92];P=6.72×10-9)。
■我们的发现有助于更好地理解脑小血管病的发病机制。此外,利用钙通道阻滞剂降低血压可有效降低WMH,BGPVS,和HIPPVS。这些发现为脑小血管病的管理和预防提供了有价值的见解。
UNASSIGNED: Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease.
UNASSIGNED: We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18 381), cerebral microbleed (3556 cases, 22 306 controls), white matter perivascular space (9317 cases, 29 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29 708 controls), and lacunar stroke (6030 cases, 248 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis.
UNASSIGNED: We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (β=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (β=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (β=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9).
UNASSIGNED: Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.