Early statin exposure influences cardiac and skeletal development with implications for ion channel transcriptomes in zebrafish.

Statins, widely prescribed for cholesterol management by inhibiting HMG-CoA reductase in the cholesterol biosynthesis pathway, may also influence vertebrate development. In this study, we investigated the developmental effects of two widely used statins, atorvastatin (ATO) and pravastatin (PRA), on zebrafish offspring. For ATO, we administered doses classified as low (1 µM), medium (5 µM), and high (10 µM), while for PRA, the corresponding concentrations were set at low (18 µM), medium (180 µM), and high (270 µM). Our results showed significant reductions in birth and hatching rates, along with decreased body length in offspring at all ATO concentrations and medium to high PRA concentrations. A notable increase in malformation rates, especially in the spine and heart, was observed across all ATO treatments and in medium and high PRA groups. Additionally, we observed reduced heart contraction rates, decreased heart size, lower bone volumes, and diminished expression of mRNA osteogenic markers. Elevated venous sinus-artery bulb (SV-BA) ratios, increased thoracic area, and abnormal cartilage development were also prominent in all ATO-treated groups. Transcriptome analysis revealed alterations in genes predominantly associated with ion channels. These findings provide insights into the potential impacts of specific concentrations of statins on offspring development and highlight potential gene interactions with statins.

Preeclampsia pravastatin early VS late treatment: Effects on oxidative stress and vascular reactivity.

Early diagnosis and efficient treatment of preeclampsia remains a medical challenge and etiological factors converge in a deficient placentation that triggers oxidative stress. There is evidence that statins show antioxidant effects that can improve endothelial function without adverse perinatal effects. We aimed to compare early vs. late pravastatin treatment on the oxidative stress and cardiovascular features of an experimental model of preeclampsia. Female Wistar rats were randomly divided into preeclampsia phenotype rats (PEP) developed by sub renal aortic coarctation (SRAC) and healthy pregnant rats (C). Each group received pravastatin (5 mg/Kg) p.o. either for one week before and during the first week or during the last two weeks of gestation. Blood pressure was determined using the plethysmographic method. Phenylephrine (Phe)-induced contractility was evaluated in isolated thoracic and abdominal aortic rings with or without endothelium. Blood samples were obtained to determine anion superoxide concentration as indicator of NADPH activity. Two-way ANOVA and Bonferroni post hoc tests were used to define statistical significance. Early or late pravastatin treatment decreased hypertension of PEP animals but did not change BP of the healthy pregnant group. Thoracic and abdominal aorta from PEP rats showed increased contractility that was reverted by pravastatin early treatment in endothelium intact rings. Pravastatin did not significantly change contractility neither in the thoracic nor in the abdominal aorta segments from healthy pregnant control rats (C), and decrease anion superoxide concentration by NADPH activity. We conclude pravastatin can improve both blood pressure and endothelium-dependent Phe-induced contractility in an experimental model of preeclampsia by reducing oxidative stress.

Challenges in Conducting Clinical Trials for Preeclampsia.

PURPOSE OF REVIEW: To review recent data describing the challenges and innovations in therapeutic research focused on the prevention and treatment of preeclampsia. RECENT FINDINGS: Pregnant individuals have traditionally been excluded from therapeutic research, resulting in a paucity of innovation in therapeutics for pregnancy-specific medical conditions, especially preeclampsia. With the increased awareness of maternal morbidity and mortality, there is significant interest among researchers to expand therapeutic research in pregnancy. Several medications, including aspirin, pravastatin, metformin, and esomeprazole, which are commonly used in non-pregnant populations, are now being investigated for preeclampsia prevention. However, given the historic precedent of exclusion, along with the regulatory, ethical, and feasibility concerns that accompany this population, the study of these and novel medications has been complicated by numerous challenges. While complex, and laden with challenges, there is great ongoing need for therapeutic research to address preeclampsia. Aspirin, pravastatin, metformin, and esomeprazole have all shown promise as potential therapeutic agents; however, their use remains to be optimized, and innovative therapeutics need to be developed.

Differential effect of atorvastatin and pravastatin on thoracic spine attenuation: A sub-analysis of a randomized clinical trial.

BACKGROUND: Statins reduce cardiovascular events and may improve bone mineral density. METHODS: We conducted a sub-analysis of a randomized clinical trial that investigated the differential effect of moderate vs intensive low-density lipoprotein cholesterol (LDL-C) lowering therapies on coronary artery calcium (CAC) scores, and used the acquired images to assess the change in radiological attenuation of selected thoracic vertebrae. Baseline and 12-month unenhanced chest CT scans were performed in 420 hyperlipidemic, postmenopausal women randomized to atorvastatin (ATV) 80 mg/day or pravastatin (PRV) 40 mg/day in the Beyond Endorsed Lipid Lowering with Electron Beam Tomography Scanning (BELLES) trial. Bone attenuation was measured in three contiguous thoracic vertebrae at baseline and 12 months. RESULTS: There were no differences in baseline demographic and clinical characteristics between treatment arms. The median percent lowering (interquartile range) in LDL-C was significantly greater with ATV than PRV [-53 (-69 to 20)% vs -28 (-55 to 74)%, p < 0.001], although the CAC score change was similar [12 (-63 to 208)% vs 13 (-75 to 358)%; p = 0.44]. At follow-up, the median bone attenuation loss was significantly greater with PRV than with ATV [-2.6 (-27 to 11)% vs 0 (-11 to 25)%; p < 0.001]. The attenuation loss in the PRV group was comparable to that of a historical untreated general population sample. In the entire cohort, the changes in LDL-C and total cholesterol were inversely correlated with bone attenuation change (p < 0.01). In adjusted multivariable linear regression analyses, race and percent change in LDL-C were independent predictors of bone attenuation change. Age, body mass index, history of smoking, diabetes mellitus, hypertension, peripheral vascular disease, or hormone replacement therapy did not affect percent change in BMD. CONCLUSIONS: These findings support the hypothesis that there is an interaction between bone and cardiometabolic health and that intensive lipid lowering has a beneficial effect on bone health.

Statin therapy in patients with early-stage autosomal dominant polycystic kidney disease: Design and baseline characteristics.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and continued growth of multiple cysts in the kidneys leading to ultimate loss of kidney function in most patients. Currently, tolvaptan is the only agency approved therapy to slow kidney disease advancement in patients with faster progressing disease underscoring the need for additional ADPKD therapies suitable for all patients. We previously showed that pravastatin slowed kidney disease progression in children and young adults with ADPKD. However, the intervention has not been tested in an adult cohort. AIMS: The aim of the study is to conduct a single center, randomized, placebo-controlled double-blinded clinical trial to determine the efficacy of pravastatin on slowing kidney disease progression in adult patients with early stage ADPKD. METHODS: One hundred and fifty adult patients with ADPKD and eGFR ≥60 ml/min/1.73m2 will be enrolled in the study and randomized to receive 40 mg/day pravastatin or placebo for a period of 2-years. OUTCOMES: The primary outcome of the trial is change in total kidney volume assessed by magnetic resonance imaging (MRI). Secondary outcomes include change in kidney function by iothalamate GFR and renal blood flow and markers of inflammation and oxidative stress. CONCLUSION: This study will assess the kidney therapeutic benefits of pravastatin in adult patients with ADPKD. The recruitment goal of 150 subjects was attained and the study is ongoing. REGISTRATION: This study is registered on Clinicaltrials.gov # NCT03273413.

Statin use reduces radiation-induced stroke risk in advanced nasopharyngeal carcinoma patients.

OBJECTIVE: This cohort study aimed to evaluate the impact of statin use on ischemic stroke risk in patients with advanced nasopharyngeal carcinoma (NPC) undergoing standard concurrent chemoradiotherapy (CCRT). METHODS: Using data from the Taiwan Cancer Registry Database, we conducted an inverse probability of treatment-weighted Cox regression analysis to examine the association between statin use during CCRT and ischemic stroke risk. RESULTS: The adjusted hazard ratio (aHR) for ischemic stroke in the statin group compared to the non-statin group was 0.70 (95 % CI: 0.54-0.92; P < 0.0107). This protective effect was observed across different statin classes, with hydrophilic statins such as pravastatin showing an aHR of 0.37 (95 % CI: 0.17-0.85) and lipophilic statins including atorvastatin displaying an aHR of 0.32 (95 % CI: 0.21-0.50) compared to non-statin use. Analysis of cumulative defined daily doses (cDDD) revealed a dose-response relationship, with lower stroke risk observed in higher quartiles of cDDD. Additionally, patients with a daily defined dose (DDD) > 1 had a reduced risk of stroke with an aHR of 0.49 (95 % CI: 0.31-0.63), while those with DDD ≤ 1 showed an aHR of 0.59 (95 % CI: 0.40-0.84). CONCLUSIONS: Our study provides evidence supporting the beneficial effects of statin use during the CCRT period in reducing radiation-induced stroke risk among patients with advanced NPC undergoing definitive CCRT. Notably, pravastatin and atorvastatin demonstrated significant reductions in stroke occurrence. Furthermore, the findings suggest a dose-response relationship, where higher cumulative doses and greater daily dose intensity of statin use were associated with a lower risk of stroke.

Statin Use During Concurrent Chemoradiotherapy With Improved Survival Outcomes in Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Nationwide Cohort Study.

INTRODUCTION: To determine the effect of statin use during concurrent chemoradiotherapy (CCRT) on overall survival and esophageal squamous cell carcinoma (ESCC)-specific survival in patients with ESCC receiving standard CCRT. METHODS: In this propensity score-matching cohort study, we used data from the Taiwan Cancer Registry Database and National Health Insurance Research Database to investigate the effects of statin use during the period of CCRT on overall survival and ESCC-specific survival. RESULTS: Statin use during the period of CCRT was found to be a considerable and independent prognostic factor for overall survival and ESCC-specific survival. The adjusted hazard ratio (aHR) for all-cause mortality in the statin group compared with that of the non-statin group was 0.65 (95% confidence interval: 0.51-0.84, p = 0.0009). The aHR for ESCC-specific mortality in the statin group compared with that of the non-statin group was 0.63 (95% confidence interval: 0.47-0.84, p = 0.0016). The use of hydrophilic statins such as rosuvastatin and pravastatin was associated with the greatest survival benefits. A dose-response relationship was also found, with higher cumulative defined daily doses and higher daily intensity of statin use associated with lower mortality. CONCLUSIONS: This study is the first to reveal that statin use during the period of CCRT for ESCC is associated with improvement in overall survival and ESCC-specific survival. In addition, we found that use of rosuvastatin, pravastatin, and simvastatin was associated with better survival outcomes for patients with ESCC receiving CCRT. Furthermore, we found a dose-response relationship of statin use associated with lower ESCC-specific mortality.

Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is an ultrarare, fatal, premature aging disease caused by a toxic protein called progerin. Circulating progerin has not been previously detected, precluding research using readily available biological samples. This study aimed to develop a plasma progerin assay to evaluate progerin's quantity, response to progerin-targeted therapy, and relationship to patient survival. METHODS: Biological samples were collected by The Progeria Research Foundation Cell and Tissue Bank from a non-HGPS cohort cross-sectionally and a HGPS cohort longitudinally. HGPS donations occurred at baseline and intermittently while treated with farnesylation inhibitors lonafarnib±pravastatin and zoledronate, within 3 sequential open-label clinical trials at Boston Children's Hospital totaling >10 years of treatment. An ultrasensitive single-molecule counting progerin immunoassay was developed with prespecified performance parameters. Intra- and interpatient group statistics were descriptive. The relationship between progerin and survival was assessed by using joint modeling with time-dependent slopes parameterization. RESULTS: The assay's dynamic detection range was 59 to 30 000 pg/mL (R2=0.9987). There was no lamin A cross-reactivity. Mean plasma progerin in non-HGPS participants (n=69; 39 male, 30 female; age, 0.2-71.3 years) was 351±251 pg/mL, and in drug-naive participants with HGPS (n=74; 37 female, 37 male; age, 2.1-17.5 years) was 33 261±12 346 pg/mL, reflecting a 95-fold increase in affected children (P<0.0001). Progerin levels did not differ by sex (P=0.99). Lonafarnib treatment resulted in an average per-visit progerin decrease from baseline of between 35% to 62% (all P<0.005); effects were not augmented by adding pravastatin and zoledronate. Progerin levels fell within 4 months of therapy and remained lower for up to 10 years. The magnitude of progerin decrease positively associated with patient survival (P<0.0001; ie, 15 000 pg/mL decrease yields a 63.9% decreased risk of death). For any given decrease in progerin, life expectancy incrementally increased with longer treatment duration. CONCLUSIONS: A sensitive, quantitative immunoassay for progerin was developed and used to demonstrate high progerin levels in HGPS plasma that decreased with lonafarnib therapy. The extent of improved survival was associated with both the magnitude of progerin decrease and duration at lower levels. Thus, plasma progerin is a biomarker for HGPS whose reduction enables short- and long-term assessment of progerin-targeted treatment efficacy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifiers: NCT00879034 and NCT00916747.

Pravastatin for severe preeclampsia with growth restriction: Placental findings and infant follow-up.

OBJECTIVE: Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading cause of premature delivery worldwide. As well as intrauterine growth restriction (IUGR), PE is associated with pathogenic evidence of placental malperfusion and ischemia. Recent literature has highlighted the potential of pravastatin in the prevention and treatment of these conditions. Aim of this study is to describe perinatal outcomes and placental histopathological findings in a small series of pregnant women with severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow up of these babies is provided. STUDY DESIGN: Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6 gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate treatment with Pravastatin 40 mg a day. Treated women were compared with controls identified with similar data in terms of gestational age at diagnosis, clinical maternal data, Doppler severity findings. Neonates were followed up for two years. RESULTS: The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the group of women treated with pravastatin, maximum transaminase, creatinine levels were lower than in controls, where the minimum platelet count was higher. Placenta examination did not reveal any significant differences in placental histopathological findings. No significant differences were observed in the investigated perinatal data, as well as in infant follow-up, although an increased prenatal weight gain was found in treated pregnancies in comparison to controls. CONCLUSIONS: Our data did not allow us to find significant differences in pregnancy outcome and infant follow-up, as well as in placental histological picture in preeclamptic patients when pravastatin is administered in the late second trimester. However, we suggest its possible role in stabilizing the disease, increasing the prenatal weight gain and prolonging the duration of pregnancy, thus preventing the progression to a more severe maternal disease.

Aspirin and Pravastatin for Preeclampsia Prevention in High-Risk Pregnancy.

Preeclampsia is a hypertensive disorder of pregnancy affecting up to 8% of pregnancies. It is associated with significant neonatal and maternal morbidities and mortality. Although its pathogenesis is not completely understood, abnormal placentation resulting in imbalance in angiogenic factors, increased inflammation, and endothelial dysfunction are thought to be key pathways in the development of the disease. Administration of low-dose aspirin is recommended by professional societies for the prevention of preeclampsia in high-risk individuals. In this review, we summarize the evidence behind the use of low-dose aspirin and pravastatin in pregnant individuals at high risk of preeclampsia.

Hair analysis as a new tool to monitor adherence to long-term therapy to statins.

Statins are cholesterol-lowering medications which are widely prescribed as first-line treatment for hyperlipidemia, against high blood cholesterol aimed at reducing the risk of atherosclerotic diseases. Notwithstanding their undoubted efficacy, the needed long-term treatment with these drugs is characterized by a high percentage of dropout. Consequently, an effective tool to verify the patients' compliance to statin therapy is needed. In this context, the analysis for drugs and drug metabolites in the hair may represent an almost ideal tool because, according to a sound body of forensic toxicological literature, concentrations in the hair matrix reflect the chronic intake of drugs and pharmaceuticals. In this light, in the present study, a novel, specific and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method has been developed to determine six statins and their metabolites (namely atorvastatin, (p)α-OH-atorvastatin-lactone, (o)α-OH-atorvastatin-lactone, rosuvastatin, N-desmethyl rosuvastatin and pravastatin) in human hair. After optimization, the method was successfully validated in terms of selectivity, linearity, sensitivity, precision, accuracy, stability and matrix effect. Moreover, the practical applicability of this method for verifying adherence to statin therapy was assessed by testing samples of hair collected from subjects under long-term therapy with statins.

A Systematic Review of Randomized Clinical Trials on the Efficacy and Safety of Pitavastatin.

BACKGROUND: A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy. AIM: The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members. METHODS: We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects. RESULTS: In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe. CONCLUSION: The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.

Adverse drug reactions of statin therapy in China from 1989 to 2019: a national database analysis.

BACKGROUND: The baseline incidence of the adverse events of statin therapy varies between countries. Notably, Chinese patients seem more susceptible to myopathy induced by simvastatin. OBJECTIVES: This research studies the adverse drug reactions (ADRs) of statin therapy in China by analysing trial-based data from the Anti-hyperlipidaemic Drug Database built by the China National Medical Products Administration Information Centre. METHODS: All clinical trials involving statin therapy (including simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin and rosuvastatin) in China from 1989 to 2019 were screened. In total, 569 clinical studies with 37 828 patients were selected from 2650 clinical trials in the database. RESULTS: Among the reported cases with ADRs (2822/37 828; 7.460%), gastrointestinal symptoms were the most common (1491/37 828; 3.942%), followed by liver disease (486/37 828; 1.285%), muscle symptoms (444/37 828; 1.174%) and neurological symptoms (247/37 828; 0.653%). Pravastatin (231/1988; 11.620%) caused the most common gastrointestinal side effects, followed by fluvastatin (333/3094; 10.763%). The least likely to cause gastrointestinal irritation was rosuvastatin (82/1846; 4.442%). CONCLUSION: In Chinese clinical trials, gastrointestinal symptoms were the most common ADR of statin use for hyperlipidaemia and other cardiovascular diseases.

Combined Administration of Pravastatin and Metformin Attenuates Acute Radiation-Induced Intestinal Injury in Mouse and Minipig Models.

Radiation-induced gastrointestinal (GI) damage is one of the critical factors that serve as basis for the lethality of nuclear accidents or terrorism. Further, there are no Food and Drug Administration-approved agents available to mitigate radiation-induced intestinal injury. Although pravastatin (PS) has been shown to exhibit anti-inflammatory and epithelial reconstructive effects following radiation exposure using mouse and minipig models, the treatment failed to improve the survival rate of high-dose irradiated intestinal injury. Moreover, we previously found that metformin (MF), a common drug used for treating type 2 diabetes mellitus, has a mitigating effect on radiation-induced enteropathy by promoting stem cell properties. In this study, we investigated whether the combined administration of PS and MF could achieve therapeutic effects on acute radiation-induced intestinal injury in mouse and minipig models. We found that the combined treatment markedly increased the survival rate and attenuated histological damage in a radiation-induced intestinal injury mouse model, in addition to epithelial barrier recovery, anti-inflammatory effects, and improved epithelial proliferation with stem cell properties. Furthermore, in minipig models, combined treatment with PS and MF ameliorates gross pathological damage in abdominal organs and attenuated radiation-induced intestinal histological damage. Therefore, the combination of PS and MF effectively alleviated radiation-induced intestinal injury in the mouse and minipig models. We believe that the combined use of PS and MF is a promising therapeutic approach for treating radiation-induced intestinal injury.

Reduction effect of oral pravastatin on the acute phase response to intravenous zoledronic acid: protocol for a real-world prospective, placebo-controlled trial.

INTRODUCTION: Zoledronic acid (ZA) has been used as a first-line treatment in patients with osteoporosis (OP) who receive an annual injection of 5 mg. However, side effects of bone pain and fever, known as the acute phase response (APR), have often been observed after clinical usage. A meta-analysis reported that the incidence of APR was 49.4% among patients with OP who received ZA for the first time and that 30% of patients with these adverse effects refused treatment in the following year. As a clinically used hypolipidaemic drug, statins can inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase to block the pathway upstream of farnesyl pyrophosphate synthase. This process can decrease the accumulation of isopentenyl pyrophosphate to prevent γδT-cell activation and inflammatory factor production, blocking APR occurrence. The aim of this study is to determine the reduction effect of oral pravastatin on APR and investigate the possible mechanisms underlying the effect in vivo. METHODS AND ANALYSIS: This will be a single-centre, placebo-controlled trial. Female participants will be allocated at a 1:1 ratio to receive either oral pravastatin or a placebo at 1-hour predose and 24 and 48 hours post-administration of ZA. The primary outcome will be the incidence of APR within 72 hours after ZA infusion. The secondary outcomes will include the occurrence time and severity of APR and the frequency and amount of acetaminophen usage within 72 hours after ZA infusion. This study will determine the preventive effect of oral pravastatin on APR in Chinese patients with OP, supporting the clinical application of ZA to alleviate concerns regarding safety and increase patient compliance. ETHICS AND DISSEMINATION: This study protocol has been registered with ClinicalTrials.gov. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee. The results will be published in scientific peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04719481.

Statins in Pregnancy: Can We Justify Early Treatment of Reproductive Aged Women?

PURPOSE OF REVIEW: Statins are the pillar of secondary prevention in reducing cardiovascular disease in high-risk adults. However, statin discontinuation is the standard recommendation in pregnant and lactating patients. This review evaluates whether we can justify the early treatment of reproductive aged women with statin therapy. RECENT FINDINGS: Statins have several potential benefits including its antioxidant, anti-inflammatory, and anti-thrombogenic properties that may prevent the worsening of atherosclerosis in high-risk women. Nevertheless, most studies on statins and teratogenicity have a limited sample size and the effects of long-term statin use on fetal and neonatal health remain unknown. Not all statins may be safe and pravastatin's cholesterol-lowering properties may be too limited to provide much maternal benefit in pregnancy. While emerging evidence supports the use of pravastatin in pregnancy, we need to better assess the risk of early cardiovascular disease and acute progression of atherosclerosis before and during pregnancy to better understand the risks and benefits of statin use.

Diet and pravastatin administration prior to in vitro fertilization treatment may improve pregnancy outcome in women with dyslipidemia.

In this study, we aimed to identify whether using statins may increase the chance of pregnancy in In Vitro Fertilisation / Intra-Cytoplasmic Sperm Injection (IVF/ICSI) patients with hyperlipidaemia. Therefore, in this retrospective cohort study, 70 patients constituted the study population and all patients were managed by lipid lowering diet. Ten mg pravastatin (pravachol DEVA, Istanbul, Turkey) was added to therapy in case of resistant hypercholesterolaemia after 15 days of the diet. Fifty-one patients were treated with diet only and the remaining nineteen patients were offered both diet and pravastatin. Clinical pregnancy rate was significantly better with the patients who used pravastatin (68.4% vs. 39.2%, p = .029). Ongoing pregnancy rates were 63.2% and 33.3% with pravastatin and diet only, respectively, which were statistically significant (p:.024). According to multivariate analysis, pravastatin use was found independently and statistically significant for clinical pregnancy and ongoing pregnancy rate after IVF/ICSI in patients with dyslipidemia (HR 3.79; 95% CI 1.31-10.97; p:.014 and HR 3.18; 95% CI 1.22-8.27; p:.018). When we analysed stratified data according to the AMH levels, we noticed that as AMH levels increased, the pregnancy rates increased; the most benefit from pravastatin was in the group with AMH levels >2 ng/mL.IMPACT STATEMENTWhat is already known on this subject? Dyslipidemia in In IVF/ICSI patients with polycystic ovary syndrome had negative impact on pregnancy ratesWhat the results of this study add? The findings of the study support that pravastatin may help to improve pregnancy outcome, especially in normal and high responders, regardless of whether decreased serum LDL or total cholesterol level.What the implications are of these findings for clinical practice and/or further research? As a result of our data, we speculated that it should be routine to investigate the lipid profile in every IVF/ICSI patient and should be treated accordingly, if necessary.

Pravastatin may improve neurological outcome following low-grade aneurysmal subarachnoid hemorrhage.

Statins may improve outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH) but randomized controlled trials, including all patients with aSAH whatever their clinical severity, were negative. We studied whether pravastatin improved neurologic outcome in patients with early good neurological status, whose prognosis is related to secondary lesions as delayed cerebral ischemia (DCI). We conducted a single-center study of cases and historical controls in a neurocritical care unit. We included consecutive patients with aSAH from 2011 to 2016 with early good neurological status defined by a WFNS score ≤ 3 on the third day. Patients treated before 2014 with oral pravastatin (40 mg/day for 14 days) as a standard of care were matched using propensity score to patients treated after 2014 without pravastatin. Good neurologic outcome was defined by a Glasgow Outcome Scale ≥ 4 at neurocritical care unit discharge. We included 270 patients (135 patients with pravastatin), mostly treated with coiling (94.1%). Demographic, initial and subacute features were the same in the 2 groups. More patients experienced good outcome in the pravastatin group than in the control group (94.8% vs 74.2%; OR 7.16 95% CI [3.07 - 16.72], p < 0.001). There was no difference in the occurrence of DCI in the 2 groups. In our study, outcome on neurocritical care discharge was better in patients with early good neurological status treated with pravastatin. Another randomized controlled trial should be conducted on this subtype of population.

Association of cognitive function with increased risk of cancer death and all-cause mortality: Longitudinal analysis, systematic review, and meta-analysis of prospective observational studies.

BACKGROUND: Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death. METHODS: Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated. RESULTS: Participants of PROSPER had 1.65-fold (95%CI 1.11-2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46-2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36-1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57-3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00-1.20, P-value = 0.044). CONCLUSIONS: Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality.