Association of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhage.

BACKGROUND: Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. AIMS: We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients' characteristics, especially ICH etiology. METHODS: Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. RESULTS: In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57-2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06-3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06-5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08-7.86). CONCLUSION: The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.

-459C>T point mutation in 5' non-coding region of human GJB1 gene is linked to X-linked Charcot-Marie-Tooth neuropathy.

Charcot-Marie-Tooth (CMT) neuropathy is inherited with genetic and clinical heterogeneity. The X-linked form (CMTX) is linked to mutations in the GJB1 gene. However, the genotype-phenotype correlation between variants in the non-coding region of GJB1 gene and CMTX is unclear. We found two structural variants (-459C>T and -713G>A) in the 5' non-coding region of a transcript (Ref seq ID: NM_000166) of the GJB1 gene and explored its association with CMTX in two Chinese families. All family members who carried the -459C>T variant either were symptomatic or had abnormal electrophysiological studies compatible with CMTX, whereas all the non-symptomatic family members who had normal electrophysiological studies and 10 healthy unrelated controls did not have this variant. The other variant in the 5'-flanking region of the gene was found to be a benign polymorphism, although it had been earlier reported to be associated with CMTX in a Taiwanese family. Secondary structure prediction analysis of mutant mRNA using M fold and RNA structure softwares indicates that the -459C>T mutation may reduce translation efficiency of the GJB1 gene by changing its 5'-untranslated region secondary structure and abolishing the internal ribosome entry site at the initialization of its translation in Schwann cells. Our study can help clarify the causal mutations of CMTX in the non-protein coding region of GJB1.

Cardiac Effects of Stroke.

Our brain regulates all bodily functions either directly or indirectly, and cardiovascular control is no exception. There is strong clinical evidence of cerebrogenic cardiac arrhythmias and myocardial changes during ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Alternative scenarios include cardioembolic stroke, multisystem diseases with stroke-like and cardiac features, and coincidental detection of cardiac disorders in a stroke patient. Cardiac effects of stroke may be severe or even fatal and worsen the prognosis. Clinical and experimental studies suggest that cortical and subcortical structures such as the insular cortex and amygdala play a pathogenic role. The peripheral mechanisms involve abnormal sympathetic activity, altered parasympathetic activity, and raised levels of circulating catecholamines, whereas the central mechanisms are largely unknown. Because stroke patients are best managed in an acute stroke unit during their initial presentation, a cardiocerebral approach is desirable with close cardiovascular and neurologic monitoring. Prolonged and intensive cardiovascular monitoring is recommended in patients manifesting cerebrogenic cardiovascular disturbances and in high-risk patients with insular involvement, right-sided stroke, advancing age, coexisting hypertensive or coronary artery disease, or intense emotional stress. Although the best management is largely unknown, treatment of cardiac effects of stroke is largely supportive according to the type of disturbance. Severely affected patients should be evaluated by a cardiologist prior to the initiation of appropriate therapy. Much more clinical and basic research is needed to allow a full understanding of the brain-heart control, the consequences of disruption of this control, the true incidence of cardiac effects of stroke, and the evidence-based treatment options.