Association of blood lipids,atherosclerosis and statin use with dementia and cognitive impairment after stroke: A systematic review and meta-analysis

BackgroundTrial and observational evidence is conflicting in terms of the association of blood lipids, atherosclerosis and statin use with dementia and cognitive impairment in the general population. It is uncertain whether the associations occur in stroke patients, who are at known higher risk of cognitive decline. This systematic review was to synthesize the evidence for these associations among stroke patients.MethodsMEDLINE, EMBASE, the Cochrane Library and trial registries were searched. We included randomized controlled trials (RCTs) or observational cohort studies conducted among patients with stroke and reported on the association of blood lipids, atherosclerosis or statin use with dementia or cognitive impairment. Meta-analysis was conducted separately for crude and maximally adjusted odds ratios (ORs) and hazard ratios (HRs).ResultsOf 18,026 records retrieved, 56 studies (one RCT and 55 cohort studies) comprising 38,423 stroke patients were included. For coronary heart disease, the pooled OR of dementia and cognitive impairment was 1.32 (95%CI 1.10–1.58, n = 15 studies, I² = 0%) and 1.23 (95%CI 0.99–1.54, n = 14, I² = 26.9%), respectively. Peripheral artery disease was associated with dementia (OR 3.59, 95%CI 1.47–8.76, n = 2, I² = 0%) and cognitive impairment (OR 2.70, 95%CI 1.09–6.69, n = 1). For carotid stenosis, the pooled OR of dementia and cognitive impairment was 2.67 (95%CI 0.83–8.62, n = 3, I² = 77.9%) and 3.34 (95%CI 0.79–14.1, n = 4, I² = 96.6%), respectively. For post-stroke statin use, the pooled OR of dementia and cognitive impairment was 0.89 (95%CI 0.65–1.21, n = 1) and 0.56 (95%CI 0.46-0.69, n = 3, I² = 0%), respectively. No association was observed for hypercholesterolemia. These results were mostly consistent with adjusted ORs or HRs, which were reported from limited evidence.ConclusionAtherosclerosis was associated with an increased risk of post-stroke dementia. Post-stroke statin use was associated with decreased risk of cognitive impairment. To confirm whether or not statins confer advantages in the post-stroke population in terms of preventing cognitive decline over and above their known effectiveness in reducing risk of further vascular events, further stroke trials including cognitive assessment and observational analyses adjusted for key confounders, focusing on key subgroups or statin use patterns are required.     

Statin use and patterns of breast cancer recurrence in the Malmö Diet and Cancer Study

BackgroundAccumulating evidence suggests that statins have a beneficial effect on breast cancer prognosis. Previous studies have reported a positive association between statin use and breast cancer survival; however, the relationship between statin use and patterns of breast cancer recurrence remains unclear.Patients and methodsWe identified all Malmö Diet and Cancer Study (MDCS) participants diagnosed with incident invasive breast cancer between 2005 and 2014. The follow-up period began at breast cancer diagnosis and continued until the first invasive breast cancer recurrence event, death, emigration or the end of the follow-up (June 8, 2020). We estimated incidence rates (IRs) of recurrence and fit Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for disease recurrence to compare post-diagnosis statin users with non-users.ResultsThe final study cohort consisted of 360 eligible patients with a median follow-up of 8.6 years. Overall, there were 71 recurrences in 2932 total person-years. According to statin use, there were 14 recurrences in 595 person-years among statin users, and 57 recurrences in 2337 person-years in non-users. Statin use was associated with a reduced risk of breast cancer recurrence (HR_adj = 0.88 [95% CI: 0.82–0.96]). Regarding the pattern of recurrence, statin use was associated with a reduced risk of distant recurrence (HR_adj = 0.86 [95% CI: 0.80–0.94]) but not loco-regional recurrence (HR_adj = 0.97 [95% CI: 0.87–1.08]).ConclusionIn the MDCS, statin use was associated with a reduced risk of distant breast cancer recurrence, whereas no association between statin use and loco-regional breast cancer recurrence was found. This site-based difference in disease recurrence may be explained by statin's inhibition of epithelial-mesenchymal transition.     

他汀类药物安全性的再评估

他汀类药物具有良好的降血脂及心血管保护功能,对于急性冠状动脉综合征患者起着重要的二级预防作用。然而,长期应用他汀类药物带来的不良反应也引起了临床医师及专家的关注。本文重新评估了他汀类药物的获益和风险,从而推动临床安全调脂的治疗。     

Serum Total Cholesterol Levels Would Predict Nosocomial Infections After Gastrointestinal Surgery

It has been suggested that total cholesterol levels and the use of statin medications are associated with the incidence of complications after gastrointestinal surgery. The aim of this study was to determine if preoperative total cholesterol levels are associated with a higher risk of postoperative infections and mortality. A total of 2211 patients undergoing general surgical procedures between December 2006 and November 2008 at Iizuka Hospital and between January 2010 and March 2012 at Jichi Medical University Hospital were reviewed. Multiple logistic regression models were used to evaluate serum total cholesterol and other variables as predictors of postoperative nosocomial infections. Serum total cholesterol concentrations lower than 160 mg/dl were associated with an increased incidence of superficial and deep incisional surgical site infections. Serum total cholesterol levels showed a reverse J-shaped relationship with the development of organ space surgical site infection and pneumonia. There was no discernible effect of serum cholesterol levels on the postoperative mortality observed in this cohort of patients. Decreased serum albumin was one of the strongest risk factors for the development of nosocomial infection after surgery. Postoperative pneumonia was not observed in patients taking statin medications whose cholesterol levels were <200 mg/dl. Serum total cholesterol may be a valid predictor of surgical outcome. Preoperative statin use may affect the development of postoperative pneumonia in patients with total cholesterol levels below 200 mg/dl.     

Effect of statin on semen quality characteristics

Statins are lipid-lowering medications widely used to reduce the risk of cardiovascular diseases. Biochemically, they act by decreasing synthesis of cholesterol via inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. Since 1992, various research studies have investigated the effect of statins on semen quality characteristics; however, to date, there is no collective summary to such effect. Here, we have systematically discussed and abridged all research studies published in Scopus, PubMed and Web of Science databases that are directly linking statin to semen fertility characteristics using the keywords “statin” versus “sperm” and “semen”. In summary, considering the animal studies, statins, in general, were found to ameliorate semen quality characteristics in reproductive detrimental conditions, while, in human males or in in vivo systems with normal reproductive conditions, in general, statins showed negative to blunt effects against semen quality characteristics, mainly sperm motility. However, further research studies, in particular human studies, in this specific research setting is still needed to approve these effects.     

The effects of systemic treatment with aminobisphosphonates and statins on circulating Vγ9Vδ2-T cells in patients with advanced cancer

Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment.