Statin Intake Research Articles

A Systematic Review and Meta-analysis of the Relationship between Statin Intake and Esophageal Cancer.

Esophageal cancer is a malignant tumor with a low survival rate. Statins, commonly prescribed for their lipid-lowering effects, have been suggested to possess potential chemopreventive properties against various cancers, including esophageal cancer. This systematic review studied the association between statin intake and esophageal cancer. To conduct this systematic review and meta-analysis, we reviewed studies published between 1980 and June 2023 in Web of Science (WOS), Embase, MEDLINE/PubMed, Scopus, and Cochrane Library databases according to the PRISMA guidelines. Data extraction, quality assessment, and statistical analyses were performed using predefined protocols. We used various statistical tests conducted by Stata statistical software. Statistical significance was considered significant at p < 0.05. Twenty-one studies were collected and analyzed. The meta-analysis demonstrated that the odds ratio (OR) of esophageal cancer in patients treated with statins was 0.65 (95% CI: 0.57-0.75, p < 0.001) compared to the non-receiving group. The ORs for case-control and cohort studies were 0.67 (95% CI:0.54-0.83, p < 0.001) and 0.62 (95% CI:0.55-0.71, p < 0.001), respectively. The investigation into the relationship between the statins intake and the incidence of esophageal cancer did not reveal any indication of publication bias according to both Begg's test (p = 0.966) and Egger's test (p = 0.113). The results revealed that the odds of esophageal cancer in patients treated with statins decreased by 35% compared to patients not treated with statins. However, further well-designed prospective studies are needed to validate these findings and understand the underlying mechanisms of statins in preventing esophageal cancer.

The Association between Statins Intake and Risk of Post Stroke Pneumonia: A Systematic Review and Meta-Analysis.

This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study. An extensive search of published articles on March 21st, 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I2) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias. Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta- analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 - 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value = 0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value = 0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282). In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia.

The influence of P2Y12 gene polymorphisms on clopidogrel therapy in patients after percutaneous coronary intervention.

Aim: We aimed to define the influence of P2Y12 polymorphisms (rs6801273, rs2046934, and rs6809699), diabetes, hypertension, obesity, hypercholesterolemia, statins intake, and smoking habit on clopidogrel therapy in patients undergoing percutaneous coronary intervention.Materials & methods: We used PCR-RFLP and PCR-ASO for P2Y12 genotype analysis. The effectiveness of the therapy was measured with the VerifyNow method and defined in platelet reactivity units.Results: Studied polymorphisms had no statistically significant influence on PRU before (PRU0) and 6 months (PRU6) after the procedure. H1/H1 diabetic carriers had significantly higher PRU6 values than patients without diabetes. Obese H1/H2 subjects had significantly lower PRU6 values than H1/H2 non-obese carriers.Conclusion: We found that obesity and diabetes may influence the long-term outcome of antiplatelet therapy.

Sex differences in lipidomic and bile acid plasma profiles in patients with and without coronary artery disease

BackgroundLipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex.MethodsFrom 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out.ResultsA total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup.ConclusionsWe present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men.Registrationhttps://clinicaltrials.gov/ct2/show/NCT04936438, Unique identifier: NCT04936438.

Unveiling Statins and Genetics in Age-Related Macular Degeneration: The Coimbra Eye Study-Report 9.

To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between statins and genetics. In this analysis, 682 subjects made two visits (6.5-year follow-up) of the Coimbra Eye Study. Subjects who started taking statins at any time point between the two visits were considered. Progressors were defined as not having AMD at baseline and having any AMD at follow-up. Genetic risk scores (GRSs) were calculated individually with 52 independent variants associated with AMD. Time to progression was estimated using unadjusted Kaplan-Meier curves. An extended Cox model was used for the association between statins and GRS with the risk for AMD progression. Multiplicative and additive interactions were assessed. Median survival time was 7.50 years for subjects not taking statins and 7.62 for subjects taking statins (P < 0.001). Statin intake reduced the risk for progression to AMD in 48%, adjusting for age, sex, body mass index, smoking, and diabetes (model 1) and GRS (model 2). The combined effects of not taking statins and having high GRS increased the progression risk fourfold compared to taking statins and having low GRS (hazard ratio [HR] = 4.25; 95% confidence interval [CI], 1.62-11.16; P = 0.003). For subjects not taking statins, an increased risk of progression was found for those subjects with high GRS compared to subjects with low GRS (HR = 1.80; 95% CI, 1.13-2.85; P = 0.013). No statistically significant multiplicative or additive interactions were found. Statins seem to be protective against AMD progression, and genetics may play a role in treatment response.

#2849 A change in the paradigm of onconephrology

Abstract Background and Aims Recently, with the emergence of checkpoint inhibitors and other new oncological therapies, the cancer paradigm has changed. These new treatment possibilities have led to an improvement in the life expectancy of patients with cancer. However, these new oncological treatments are often linked to adverse renal events that require a specifical nephrological evaluation at the onconephrology units. These renal adverse events may increase the morbidity and mortality of cancer patients. Therefore, the aim of this study was to analyze the changes in renal involvement of patients with solid organ malignancy who underwent kidney biopsy after the onset of new oncological therapies. Method A retrospective observational study was performed analyzing kidney biopsies conducted in a 9.2-year period. This study included patients with history of solid organ malignancy before and one year after kidney biopsy. All the results are represented as mean ± standard deviation for variables with a normal distribution, or in percentage (%). Normality was assessed by the Shapiro-Wilk test. Group comparisons were conducted using Student´s t test for normally distributed quantitative variables and chi-square for qualitative variables. The statistical software utilized was SPSS version 27. Results Six patients who underwent a kidney biopsy before 2019 (Group A) were compared to 22 patients who underwent a kidney biopsy in 2019 and after (Group B). In Group A, the mean age was 68.5 ± 7.1 years old, while in Group B, it was 70.7 ± 7.1. In Group A, there was a predominance of females (66.7%), whereas in Group B, there was a higher proportion of males (81.8%). In Group A, higher intake of statins and acetylsalicylic acid were observed compared to Group B (83.3% vs. 31.8%, p = 0.024; 33.3% vs. 4.5%, p = 0.043). At the time of kidney biopsy, concerning the history of solid organ malignancy, 66.7% patients in Group A were disease-free, while in Group B they were predominantly stable (50%) (p &amp;lt; 0.001). In Group A, all nephropathies were caused by factors unrelated to oncological disease, while in Group B 63.6% nephropathies were secondary to oncospecific treatment (p = 0.003). In Group A, longer time from oncological diagnosis to death was observed compared to Group B (3033 ± 1889.09 days vs. 692 ± 719.47 days, p = 0.012). Regarding renal function at the time of kidney biopsy, we observed predominantly normal or stable renal function in Group A (66.7%), while Group B showed a higher frequency of renal dysfunction (77.3%) (p = 0.041); resulting in creatinine levels of 1.82 ± 0.68 mg/dl in Group A and 3.95 ± 2.48 mg/dl in Group B (p = 0.049). Finally, kidney biopsies in Group A showed acute tubular necrosis and acute or chronic tubulointerstitial nephritis in 16.7%, while in Group B these diagnoses were found in 81.8% of kidney biopsies (p = 0.002). Conclusion After the onset of new oncospecific therapies, the paradigm of kidney disease in cancer patients in terms of diagnosis and treatment has changed. Kidney biopsy may be a useful diagnostic and prognostic tool. But also, a specialized onconephrologist may have a key role to discern the different etiologies of kidney damage and provide the best management to these patients. This new trend may lead to a growth and an empowerment of onconephrology subspecialty.

Statins did not reduce the frequency of exacerbations in individuals with COPD and cardiovascular comorbidities in the COSYCONET cohort

BackgroundThe evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities.MethodsOne thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1–4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up.ResultsOne thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year.ConclusionThese findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency.Trial registrationTrial registration ClinicalTrials.gov, Identifier: NCT01245933.Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010–11, primary completion 2013–12, study completion 2023–09.https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3

Unsupervised Machine Learning Revealed that Repeat Transcranial Magnetic Stimulation is More Suitable for Stroke Patients with Statin.

Repeat transcranial magnetic stimulation (rTMS) demonstrates beneficial effects for stroke patients, though its efficacy varies due to the complexity of patient conditions and disease progression. Unsupervised machine learning could be the optimal solution for identifying target patients for transcranial magnetic stimulation treatment. We collected data from ischaemic stroke patients treated with rTMS. Unsupervised machine learning methods, including K-means and Hierarchical Clustering, were used to explore the clinical characteristics of patients suitable for rTMS. We then utilized a prospective observational cohort to validate the effect of selected characteristics. For the validated cohort, outcomes included the presence of motor evoked potentials (MEP), favorable functional outcomes (FFO), and changes in the Fugl-Meyer Assessment (FMA) at 3 and 6months. Hierarchical clustering methods revealed that patients in the better prognosis group were more likely to take statins. The validated cohort was grouped based on statin intake. Patients taking statins exhibited a higher rate of MEP (p = 0.006), a higher rate of FFO at 3months (p = 0.003) and 6months (p = 0.021), and a more significant change in FMA (p < 0.001) at both 3 and 6months. Statin intake was associated with FFO and changes in FMA at 3 and 6months. This relationship persisted across all subgroups for FMA changes and some FFO subgroups. Stroke patients undergoing rTMS treatment taking statins exhibited greater MEP, FFO, and changes in FMA. Statin intake was associated with a better prognosis in these patients.

Impact of demographic factors, comorbidities, and co‐medication on progression and survival in a large Chinese ALS cohort

AbstractObjectiveTo clarify the impact of specific risk/protective factors on the disease progression and survival in a large population of Chinese sporadic ALS (sALS) patients.MethodsWe investigated a cohort of 937 sALS patients prospectively. Uni‐ and multivariate regression analysis were performed to analyze the influence of demographic factors, comorbidities and medication on the progression and survival of ALS.ResultsOur results showed younger age of onset (p &lt; 0.05), long diagnostic delay (p &lt; 0.001) and intake of riluzole (p &lt; 0.001) were significantly related to low progression rate and long survival time. History of smoking (p &lt; 0.05) and bulbar onset (p &lt; 0.001) were risk factors for rapid progression and poor prognosis. Baseline ALSFRS‐R score (p &lt; 0.001) and total MRC score (p &lt; 0.05) were positively related to mean survival time of included patients. Neither comorbidities nor intake of antihypertensive drugs, antidiabetics, and statins as dependent variables showed considerable influence on ALS progression or survival.ConclusionOur study revealed early onset and long diagnostic delay were indicators of slow progression and long survival. Smoking and bulbar onset were risk factors for shorter survival times and abstaining from smoking was beneficial to patients with ALS in improving median survival time. Long‐term intake of riluzole should be recommended for affordable patients.

The Relationship between Statin Intake and Risk of Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Pancreatic neoplasm is one of the types of cancer with a high incidence and case-fatality rate. This study was designed to investigate the relationship between statin intake and the risk of pancreatic cancer with a systematic review and meta-analysis approach. This study was a systematic review and meta-analysis of studies published before 2023 in Cochrane Library, Web of Science (WOS), PubMed, Google Scholar, ScienceDirect, Scopus, and Embase databases. The statistical analyses were conducted using Stata software, version 15. The significance level for this study was set at 0.05. This meta-analysis included 32 studies and a total of 5,849,814 participants. The risk ratio (RR) of pancreatic cancer in comparison to the non-statin receiving group in statin users in total was equal to 0.75 (95% CI: 0.66-0.86, p-value <0.001), in the cohort studies was obtained to be 0.70 (0.53-0.93), in the randomized clinical trials (RCTs) had a ratio of 0.99 (0.53-1.86), while studies conducted in American countries had a ratio of 0.69 (0.51-0.93), studies in Asian countries had a ratio of 0.73 (0.56-0.97), and studies in European countries had a ratio of 0.88 (0.76-1.02). Furthermore, the study did not detect any signs of publication bias. The study findings suggest a potential connection between using statins and a lower risk of pancreatic cancer. However, it is important to note that controlled clinical trials did not find a statistically significant association between taking statins and the development of pancreatic cancer. Therefore, it is advisable to exercise caution when interpreting the results of this study.

Changes in Dickkopf-1, but Not Sclerostin, in Gingival Crevicular Fluid Are Associated with Peroral Statin Treatment in Patients with Periodontitis.

Background and Objectives: Periodontitis is marked by the destruction of alveolar bone. Sclerostin (SOST) and dickkopf-1 (DKK-1) act as inhibitors of the Wingless-type (Wnt) signaling pathway, a key regulator of bone metabolism. Recent studies have suggested that statins play a role in bone resorption and formation by influencing Wnt signaling. The aim of this study was to determine the levels of SOST and DKK-1 in periodontal patients with and without peroral statins treatment in their therapy. Materials and Methods: A total of 79 patients with diagnosed periodontitis were divided into two groups: 39 patients on statin therapy (SP group) and 40 patients without statin therapy as a control group (P group). The periodontal clinical examination probing (pocket) depth (PD) and gingival recession (GR) were measured, and approximal plaque was detected, while vertical and horizontal bone resorption was measured using a panoramic radiograph image. Clinical attachment loss (CAL) values were calculated using PD and GR values. Gingival crevicular fluid (GCF) was collected and used for measuring SOST and DKK-1 levels. A questionnaire was used to assess lifestyle habits and statin intake. Patients' medical records were used to obtain biochemical parameters. Results: There was no significant difference in sclerostin concentration between the SP and P group. DKK-1 values were significantly higher in the SP group compared to the control group (p = 0.04). Also, PD (p = 0.001) and GR (p = 0.03) were significantly higher in the SP group. The level of DKK-1 had a positive relationship with the PD, the greater the PD, the higher the level of DKK-1 (Rho = 0.350), while there was no significant association with other parameters. Conclusions: Peroral statins in periodontal patients are associated with GCF levels of DKK-1 but not with sclerostin levels.

Apolipoprotein A-IV concentrations and cancer in a large cohort of chronic kidney disease patients: results from the GCKD study

BackgroundChronic kidney disease (CKD) is highly connected to inflammation and oxidative stress. Both favour the development of cancer in CKD patients. Serum apolipoprotein A-IV (apoA-IV) concentrations are influenced by kidney function and are an early marker of kidney impairment. Besides others, it has antioxidant and anti-inflammatory properties. Proteomic studies and small case–control studies identified low apoA-IV as a biomarker for various forms of cancer; however, prospective studies are lacking. We therefore investigated whether serum apoA-IV is associated with cancer in the German Chronic Kidney Disease (GCKD) study.MethodsThese analyses include 5039 Caucasian patients from the prospective GCKD cohort study followed for 6.5 years. Main inclusion criteria were an eGFR of 30–60 mL/min/1.73m2 or an eGFR > 60 mL/min/1.73m2 in the presence of overt proteinuria.ResultsMean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dL (median 27.6 mg/dL). 615 patients had a history of cancer before the enrolment into the study. ApoA-IV concentrations above the median were associated with a lower odds for a history of cancer (OR = 0.79, p = 0.02 when adjusted age, sex, smoking, diabetes, BMI, albuminuria, statin intake, and eGFRcreatinine). During follow-up 368 patients developed an incident cancer event and those with apoA-IV above the median had a lower risk (HR = 0.72, 95%CI 0.57–0.90, P = 0.004). Finally, 62 patients died from such an incident cancer event and each 10 mg/dL higher apoA-IV concentrations were associated with a lower risk for fatal cancer (HR = 0.62, 95%CI 0.44–0.88, P = 0.007).ConclusionsOur data indicate an association of high apoA-IV concentrations with reduced frequencies of a history of cancer as well as incident fatal and non-fatal cancer events in a large cohort of patients with CKD.Graphical

Unused potential of lipid-lowering therapy in very high-risk patients with atherosclerotic cardiovascular disease. A retrospective data analysis

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is the most common cause of death in Europe. Although the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias claim a target low-density lipoprotein cholesterol (LDL-C) value of <55 mg/dL for very high-risk patients by use of lipid-lowering therapy (LLT) and lifestyle adaptations, the target level achievement is not satisfactory. We examined LLT use in ASCVD patients exceeding LDL-C target levels at admission and its adaptations at discharge. Methods and resultsBetween January 2017 and February 2020, 1091 patients with LDL-C >100 mg/dL and ASCVD defined as diagnosis of angina pectoris (AP, n = 179), acute myocardial infarction (AMI, n = 317), chronic ischemic heart disease (CHD, n = 195), or peripheral artery disease (PAD, n = 400) were extracted from hospital records. LLT use on admission and discharge as well as recommendations on lifestyle and nutrition were analysed.On admission, 51% of the patients were not taking LLT. At discharge, 91% were prescribed statins and 87% were advised on lifestyle adaptation and/or pharmacological treatment. High-intensity statin use at discharge was present in 63% of the AP-group, 92% of the AMI-group, 62% of the CHD-group and 71% of the PAD-group. Ezetimibe was present in 16% and proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) in 1%. However, of those on high-intensity statin, 25% remained on insufficient statin dosage. ConclusionSwitch to high-intensity statins and use of ezetimibe and PCSK9i was low in chronic ASCVD patients. Even though statin intake was high in high-risk patients, target levels were still not reached.

Statin Use and Liver Cancer Risk: A Meta-Epidemiological Study of Retrospective Cohort Studies by the Types of Constructed Cohort.

Previous systematic reviews of retrospective cohorts (RSC) indicate that statin use decreases the risk of liver cancer. However, the summary effect size (sES) of the randomized controlled trials was not statistically significant. This study aimed to conduct a subgroup meta-analysis based on the types of constructed cohorts. RSCs were selected from previous systematic reviews. Based on the characteristics of the source database (national vs. hospital) and the selection criteria of the subjects (population vs. patients), RSCs were categorized into three types of study cohorts: a national-based population cohort (NPo), national-based patient cohort (NPa), and hospital-based patient cohort (HPa). The sES and 95% confidence intervals were calculated using a random-effects model. The 28 cohorts from 23 RSC were classified into 15 NPa, 7 NPo, and 6 HPa. The sES of 15 NPa decreased the liver cancer risk with statin intake history with statistical significance, but 7 NPo lost statistical significance. The lack of statistical significance in NPo supports the argument that the conclusions of existing systematic reviews on RSC have low validity. It is necessary to conduct a subgroup meta-analysis of the NPo, NPa, and HPa proposed in this study when conducting a systematic review of RSCs, which will evaluate various outcomes of a specific drug intake with time-varying exposure.

Clinical and genetic diagnosis of familial hypercholesterolaemia in patients undergoing coronary angiography: the Ludwigshafen Risk and Cardiovascular Health Study.

To investigate the prevalence of familial hypercholesterolaemia (FH) and compare the performance of clinical criteria and genetic testing in patients undergoing coronary angiography. The prevalence of FH was determined with the Dutch Lipid Clinical Network (DLCN), US-MEDPED, Simon Broome (SB) criteria, the 'Familial Hypercholesterolaemia Case Ascertainment Tool' (FAMCAT), and a clinical algorithm. Genetic screening was conducted with a custom array from Affymetrix (CARRENAL array) harboring 944 FH mutations. The study cohort consisted of 3267 patients (78.6% with coronary artery disease [CAD]). FH was diagnosed in 2.8%, 2.2%, 3.9%, and 7.9% using the DLCN, US-MEDPED, SB criteria, and the FAMCAT. The clinical algorithm identified the same patients as the SB criteria. Pathogenic FH mutations were found in 1.2% (1.2% in patients with CAD, 1.0% in patients without CAD). FH was more frequently diagnosed in younger patients. With genetic testing as reference, the clinical criteria achieved areas under the ROC curve (AUCs) in the range of 0.56-0.68. Using only LDL-C corrected for statin intake, an AUC of 0.68 was achieved. FH is up to fourfold more prevalent in patients undergoing coronary angiography than in contemporary cohorts representing the general population. Different clinical criteria yield substantially different diagnosis rates, overestimating the prevalence of FH compared to genetic testing. LDL-C testing alone may be sufficient to raise the suspicion of FH, which then needs to be corroborated by genetic testing.

Possible association between β-blocker use and a risk of intracranial aneurysm rupture.

Aneurysmal subarachnoid hemorrhage is a devastating type of stroke, associated with high mortality and morbidity. One of modifiable risk factors of aneurysm rupture is hypertension, however, it is still not clear whether any particular antihypertensive drugs play a significant role in the prevention of aneurysm rupture. We decided to investigate whether there is any association between acetylsalicylic acid, α-blockers, β‑blockers, angiotensin‑converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, statins, and anticoagulants and a risk of intracranial aneurysm rupture. We retrospectively analyzed 334 patients with ruptured and unruptured intracranial aneurysm. Based on logistic regression models, we obtained unadjusted and adjusted odds ratios (ORs) of subarachnoid hemorrhage associated with the use of vasoactive medications and with indices of tortuosity. We found that β‑blocker intake was significantly related to higher tortuosity of the cerebral arteries. Also, the intake of β‑blockers (OR, 0.41; 95% CI, 0.21-0.77; P = 0.01) and statins (OR, 0.23; 95% CI, 0.05-0.68; P = 0.01) significantly decreased the risk of aneurysm rupture, a result driven by a decreased rupture risk of anterior circulation aneurysms. No such association was found for the posterior part of the cerebral circulation. Aneurysm located in the anterior cerebral circulation might be less likely to rupture if patients receive β‑blockers or statins.

Statin-associated muscle symptoms : performance and quality of life

Statins use is linked to side effects, notably muscular ones, known as Statin-Associated Muscle Symptoms (SAMS). These can include a pain, an increased sensitivity to palpation, aches, and cramps. SAMS are a real problem in the clinical management of patients, as it is difficult to causally link these complaints with drug use, and they may lead to a reduction in statin intake, or even to the patient -discontinuing their use. The absence of objective markers and the -variety of possible clinical manifestations of these muscular -complaints impede a full understanding of the objective and -subjective impacts of these symptoms on the everyday life of sympto-matic patients. This article assess the current state of knowledge on the impact of SAMS on performance and health--related quality of life.

ApoB-specific CD4+ T cells circulate in human blood and formation of a memory population is driven by coronary artery disease and an elevated cardiovascular risk profile

Abstract Aim Atherosclerosis is a chronic inflammatory disease involving an autoimmune response against Apolioprotein B (ApoB), the core protein of low-density lipoprotein (LDL) cholesterol. Using a translational bench-to-bedside approach, we linked the presence and immuno-phenotype of ApoB-specific CD4+ T cells to clinical risk profiles for cardiovascular disease in humans. Methods Peripheral blood mononuclear cells (PBMCs) from 230 patients that underwent coronary angiography were co-incubated in vitro with a pool of immunodominant peptides from human ApoB for 6h. Reactive ApoB-specific T cells (ApoB+) were defined in flow cytometry by expression of the activation marker CD40L. Partition of ApoBpos into naïve and memory T cells was achieved by extracellular fluorochrome-based staining of CD45RO, CCR7 and CD45RA. Cytokine expression of ApoBpos was determined by intracellular staining. Results We found that a median of 0.69±0.1% of circulating CD4+ T cells were reactive to Apolipoprotein B. We found detectable concentrations of auto reactive ApoB+ T cells in 86,44% of all healthy individuals. However, overall frequencies of ApoB reactive T cells did not correlate with diagnosed coronary artery disease (CAD). Compared to ApoBneg. T cells, we detected a higher fraction of memory T cells in ApoBpos (p&amp;lt;0,0001), suggesting a previously occurred ApoB directed immune response. Accordingly, elevated serum levels of ApoB specific IgG Antibodies associated with high proportions of ApoB specific memory cells. Patients diagnosed with coronary artery disease presented higher percentages of central memory T cells among ApoBpos compared to healthy individuals. Correspondingly, these observations applied to patients with an elevated 10-year risk for cardiovascular events estimated by the ESC-SCORE2. These effects largely grounded on strong associations with the clinical diagnosis of arterial hypertension, elevated levels of Lp(a) and obesity. Interestingly, systolic blood pressure and LDL-serum levels correlated with elevated proportions of memory-status ApoBpos T cells in patients without statin intake, although this was not the case for patients with LDL-lowering medication. Analysis of cytokine expression in ApoBpos CD4+ T cells showed significantly increased expression of anti-inflammatory Il-2 and IL-10 in addition to pro-inflammatory IFNγ. Cytokine secretion was mainly driven by memory-status ApoBpos when compared to naïve ApoBpos T cells. Interestingly, a significant number of patients showed a mixed TH1/Treg phenotype among ApoBpos with simultaneous expression of IL-10 and IFN-γ. Conclusions Our data show for the first time that ApoB-reactive T cells exist even in healthy individuals. Cardiovascular risk factors and clinically relevant atherosclerotic disease drive memory formation and activation of ApoB+ T cells. ApoB+ Memory T cells are prone to secrete pro- and anti-inflammatory cytokines and may modulate systemic inflammation in atherosclerosis.

Analysis of Methylglyoxal Concentration in a Group of Patients with Newly Diagnosed Prediabetes.

The abnormal serum concentration of methylglyoxal (MGO) has been presented as an indicator of chronic complications in diabetes (DM). Because such complications are also found in pre-DM, we decided to assess the concentration of this compound in individuals with pre-DM, without cardio-vascular diseases. Frozen samples from individuals newly diagnosed with pre-DM (N = 31) and healthy subjects (N = 11) were prepared and MGO concentration was determined using UHPLC-ESI-QqTOF-MS. Statistical significance was established when the groups were compared for body weight, BMI, fasting glucose level, fatty liver and use of statins but not for the other descriptive parameters. The positive linear correlation showed that the higher HbA1c, the higher MGO concentration (p = 0.01). The values of MGO were within the normal range in both groups (mean value for pre-DM: 135.44 nM (±SD = 32.67) and for the control group: 143.25 nM (±SD = 17.93); p = 0.46 (±95% CI)), with no statistical significance between the groups. We did not confirm the elevated MGO levels in the group of patients with pre-DM. The available data suggests a possible effect of statin intake on MGO levels. This thesis requires confirmation on a larger number of patients with an assessment of MGO levels before and after the introduction of statins.

Statins, commonly coprescribed drugs, and concomitant risk factors: A protective, neutral, or harmful association with common cancer types development: A 10-year multicentric retrospective lebanese study.

Elevated blood levels of low-density lipoprotein cholesterol are a major cardiovascular risk factor, and cholesterol-lowering drugs are among the most prescribed drugs worldwide. Cancer is the second leading cause of death after cardiovascular diseases. The relationship between cancer development and statins intake is controversial, and there are no clear studies in Lebanon and the Middle East concerning this topic. Hence, our study aimed to search for any possible association of statin intake as well as other medications (proton pump inhibitors [PPI], metformin, Aspirin, Angiotensin-Converting Enzyme inhibitors, and fenofibrate) with lung, colorectal cancer (CRC), and bladder cancer development in the Lebanese population. A retrospective study was performed on 709 subjects divided into 2 main groups: control (no cancer ± statin intake), and cases (either lung, or colorectal, or bladder cancer ± statin intake). Collected data included the age and gender of the patient, socioeconomic status, presence of cardiovascular disease and comorbidities, cancer risk factors, and the intake type, dose, and duration of statins. Bivariate, multivariate, and binary logistic analyses were enrolled. Out of 709 participants, 63.2% were males and 75% were cancer-positive (24.1%: lung cancer, 26.7%: CRC, 24.1%: bladder cancer). The overall intake of statins was not shown to significantly affect cancer development. However, a duration-response relationship was established between Simvastatin and lung cancer (odds ratio [OR]=1.208) as well as bladder cancer (OR=1.189). No significant association was found between each statin and CRC. Although PPIs intake was associated with a possibly harmful effect on lung cancer development (OR=3.42), it revealed a protective association with CRC development (OR=0.38). Other risk factors such as smoking and age were strongly associated (harmful) with lung and bladder cancer development. Physical inactivity and a family history of CRC were each associated with a harmful effect on CRC development. A harmful association with the development of lung and bladder cancer was found with the increasing duration of intake of Simvastatin. Other drugs such as PPIs and specific risk factors were also associated negatively or positively with the development of these 3 cancers. These findings should be validated by further investigations to guide clinicians on optimal treatment options for their patients.