Effect of the Blood Pressure and Antihypertensive Drugs on Cerebral Small Vessel Disease: A Mendelian Randomization Study.
Stroke
; 55(7): 1838-1846, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38818733
ABSTRACT
BACKGROUND:
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.METHODS:
We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757â 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18â 381), cerebral microbleed (3556 cases, 22â 306 controls), white matter perivascular space (9317 cases, 29â 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29â 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29â 708 controls), and lacunar stroke (6030 cases, 248â 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis.RESULTS:
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 (ß=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 (ß=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 (ß=-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).CONCLUSIONS:
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Pressão Sanguínea
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Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Análise da Randomização Mendeliana
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Doenças de Pequenos Vasos Cerebrais
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Anti-Hipertensivos
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article