Effects of sartans and low-dose statins on cerebral white matter hyperintensities and cognitive function in older patients with hypertension: a randomized, double-blind and placebo-controlled clinical trial

Zhang, Hua; Chen, Yi; Zhao, Yong; Dong, Yuanli; Duan, Dandan; Wang, Juan; Shen, Lin; Ji, Tiantian; Zhou, Tingting; Hu, Wenjing; Chen, Yali; Sun, Shan; Gong, Gary; Chai, Qiang; Liu, Zhendong

doi:10.1038/s41440-018-0165-7

Cited by 49 publications

(73 citation statements)

References 47 publications

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“…In the Perindopril protection against recurrent stroke study (PROGRESS), use of perindopril or indapamide led to a benefit in dementia reduction among individuals with recurrent stroke [ 58 ]. In a recent study, telmisartan (an AT1R blocker) synergistically interacted with low-dose rosuvastatin to reduce white matter hypertensive progression and cognitive function decline [ 59 ]. Contrasting findings are available with the new pharmacological approach based on neprilysin inhibition in association with an AT1R blocker (ARNi) [ 60 ].…”

Section: Nps Cognitive Impairment and Dementia: Implications In Hmentioning

confidence: 99%

Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension

Gallo

Bianchi

Cotugno

et al. 2020

JCM

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The natriuretic peptides (NPs) belong to a family of cardiac hormones that exert relevant protective functions within the cardiovascular system. An increase of both brain and atrial natriuretic peptide levels, particularly of the amino-terminal peptides (NT-proBNP and NT-proANP), represents a marker of cardiovascular damage. A link between increased NP levels and cognitive decline and dementia has been reported in several human studies performed both in general populations and in cohorts of patients affected by cardiovascular diseases (CVDs). In particular, it was reported that the elevation of NP levels in dementia can be both dependent and independent from CVD risk factors. In the first case, it may be expected that, by counteracting early on the cardiovascular risk factor load and the pathological processes leading to increased aminoterminal natriuretic peptide (NT-proNP) level, the risk of dementia could be significantly reduced. In case of a link independent from CVD risk factors, an increased NP level should be considered as a direct marker of neuronal damage. In the context of hypertension, elevated NT-proBNP and mid-regional (MR)-proANP levels behave as markers of brain microcirculatory damage and dysfunction. The available evidence suggests that they could help in identifying those subjects who would benefit most from a timely antihypertensive therapy.

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Section: Nps Cognitive Impairment and Dementia: Implications In Hmentioning

confidence: 99%

Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension

Gallo

Bianchi

Cotugno

et al. 2020

JCM

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“…Therefore, BP control is crucial for the prevention of WMH. Despite the presence of a few conflicting voice, in recent years, emerging evidence has shown the benefit of more intensive BP control in terms of cerebrovascular events and WMH 8‐14 …”

Section: Introductionmentioning

confidence: 99%

Effect of intensive blood pressure control on the prevention of white matter hyperintensity: Systematic review and meta‐analysis of randomized trials

Lai

Jiang

et al. 2020

J of Clinical Hypertension

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Hypertension is an important cause of cerebral small vessel disease, especially of white matter hyperintensity (WMH). The ability of intensive blood pressure (BP) control in preventing this pathological progression remains unclear. The authors systematically searched PubMed, EMBASE, SCOPUS, and Cochrane library for publications until July 20, 2020. Studies included were clinical trials with random allocation to an antihypertensive medication against placebo, or different treatment targets. The primary outcome was intergroup differences in the change of WMH volume. A random‐effect model was applied for pooling effect measures. Subgroup analysis and meta‐regression were conducted to explore heterogeneity. Seven studies with 2693 patients were identified. Compared with the control group, patients in the intensive BP control group had a slower progression of WMH, with a pooled intergroup standard mean difference (SMD) for WMH change of −0.22 (95% CI: −0.35 ~ −0.09, I2 = 63%). For studies comparing intensive and standard BP target, the pooled SMD is −0.37 (95% CI:‐0.50~‐0.24, I2 = 0%), while the pooled SMD of studies comparing active antihypertensive medication and placebo was only −0.08 (95% CI: −0.17 ~ 0.01, I2 = 0%). Meta‐regression analysis showed that the reduction in WMH progression is proportional to the magnitude of intensive BP control (β = −0.028, P < .001). In conclusion, intensive BP control prevents WMH progression, and its effect is associated with the magnitude of intensive BP control.

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“…Some prominent features associated with CSVD include white matter hyperintensities (WMH), lacunes, enlarged perivascular space (EPVS), and microbleeds observed through magnetic resonance imaging (MRI) [ 5 , 6 ]. CSVD is responsible for 25–30% of all cerebral strokes and as much as 45% of all dementia [ 1 , 7 ]; it is also frequently associated with mood disorders and gait problems [ 1 , 7 – 9 ]. CSVD poses a high burden on individuals and society worldwide.…”

Section: Introductionmentioning

confidence: 99%

“…CSVD is strongly associated with cardiovascular risk factors including hypertension, hyperlipidemia, and aging [ 1 , 9 – 11 ]. However, the results of the Rotterdam Scan Study have demonstrated that blood pressure is not associated with WMH progression and incident lacunar infarcts in the oldest people [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…A recent meta-analysis [ 17 ] has indicated that statins produce significant decreases in major vascular events irrespective of age. Other studies [ 7 – 9 , 18 ] have demonstrated that statins are independent beneficial factors alleviating the progression of CSVD. However, there is less direct evidence of the benefits of statin therapy for slowing the progression of CSVD among people older than 75 years because the adverse effect risks of statins, such as frailty, liver injury, and myalgias are more serious in adults ≥75 than < 75 years of age [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Assessing the effectiveness of statin therapy for alleviating cerebral small vessel disease progression in people ≥75 years of age

Guo

Liu

et al. 2020

BMC Geriatr

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Background Statins have been recommended by several guidelines as the primary prevention medication for cardiovascular diseases. However, the benefits of statin therapy for cerebral small vessel disease (CSVD), particularly in adults ≥75 years of age, have not been fully evaluated. Methods We analyzed the data from a prospective population-based cohort study and a randomized, double-blind, placebo-controlled clinical trial to determine whether statin therapy might aid in slowing the progression of CSVD in adults ≥75 years of age. For the cohort study, 827 participants were considered eligible and were included in the baseline analysis. Subsequently, 781 participants were included in follow-up analysis. For the clinical trial, 227 participants were considered eligible and were used in the baseline and follow-up analyses. Results The white matter hyperintensities (WMH) volume, the WMH-to-intracranial volume (ICV) ratio, the prevalence of a Fazekas scale score ≥ 2, lacunes, enlarged perivascular spaces (EPVS), and microbleeds were significantly lower in the statin group than the non-statin group at baseline in the cohort study (all P < 0.05). During the follow-up period, in both the cohort and clinical trial studies, the WMH volume and WMH-to-ICV ratio were significantly lower in the statin/rosuvastatin group than the non-statin/placebo group (all P < 0.001). Statin therapy was associated with lower risk of WMH, lacunes, and EPVS progression than the non-statin therapy group after adjustment for confounders (all P < 0.05). There was no statistically significant difference in the risk of microbleeds between the statin and non-statin therapy groups (all, P > 0.05). Conclusions Our findings indicated that statin therapy alleviated the progression of WMH, lacunes, and EPVS without elevating the risk of microbleeds. On the basis of the observed results, we concluded that statin therapy is an efficient and safe intervention for CSVD in adults ≥75 years of age. Trial registration Chictr.org.cn: ChiCTR-IOR-17013557 , date of trial retrospective registration November 27, 2017 and ChiCTR-EOC-017013598 , date of trial retrospective registration November 29, 2017.

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Effects of sartans and low-dose statins on cerebral white matter hyperintensities and cognitive function in older patients with hypertension: a randomized, double-blind and placebo-controlled clinical trial

Cited by 49 publications

References 47 publications

Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension

Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension

Effect of intensive blood pressure control on the prevention of white matter hyperintensity: Systematic review and meta‐analysis of randomized trials

Assessing the effectiveness of statin therapy for alleviating cerebral small vessel disease progression in people ≥75 years of age

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