PURPOSE: Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (< 70 vs. < 55 mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated. METHODS: DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of < 70 or < 55 mg/dl (LDL-C of 69 or 54 mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs and ARRs) were simulated. RESULTS: Of the 2039 patients, 61% did not achieve LDL-C < 70 mg/dl. For patients with LDL-C ≥ 70 mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54 mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively. CONCLUSION: In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach.

• Klíčová slova
• Atherosclerotic cardiovascular disease, Cardiovascular disease prevention, Cardiovascular risk, LDL-C, Lipid-lowering, Statins,
• MeSH
• ateroskleróza * diagnóza   farmakoterapie   epidemiologie   MeSH
• chování snižující riziko MeSH
• kardiovaskulární nemoci * diagnóza   epidemiologie   prevence a kontrola   MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• statiny * terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Geografické názvy
• Spojené státy americké epidemiologie   MeSH
• Názvy látek
• LDL-cholesterol MeSH
• statiny * MeSH

Coronary artery disease (CAD) together with stroke are the leading causes of death worldwide, and together, they pre-sent a health and economic burden. Ischemic stroke survivors and patients who suffered transient ischemic attack (TIA) have a higher prevalence of coronary atherosclerosis, and they have a relatively high risk of myocardial infarcti-on and nonstroke vascular death. Pubmed was searched for studies focused on investigating coronary atherosclerosis in ischemic stroke survivors or patients who suffered TIA and their cardiovascular risk assessment. There were corona-ry plaques in 48%-70% of stroke survivors without a known history of CAD, and significant stenosis of at least one coronary artery can be found in 31% of these patients. CAD is a major cause of morbidity and mortality in stroke survivors. Detection and treatment of silent CAD may improve the long-term outcome and survival of these patients.

• MeSH
• cévní mozková příhoda * MeSH
• ischemická cévní mozková příhoda * MeSH
• ischemie mozku * MeSH
• lidé MeSH
• rizikové faktory MeSH
• tranzitorní ischemická ataka * komplikace   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

• Klíčová slova
• Genetic association studies, LDL-cholesterol, Mendelian randomisation, Phenome-wide association scan,
• MeSH
• anticholesteremika škodlivé účinky   terapeutické užití   MeSH
• biologické markery krev   MeSH
• celogenomová asociační studie MeSH
• cévní mozková příhoda epidemiologie   prevence a kontrola   MeSH
• down regulace MeSH
• dyslipidemie krev   farmakoterapie   epidemiologie   genetika   MeSH
• hodnocení rizik MeSH
• infarkt myokardu epidemiologie   prevence a kontrola   MeSH
• inhibitory serinových proteinas škodlivé účinky   terapeutické užití   MeSH
• ischemie mozku epidemiologie   prevence a kontrola   MeSH
• jednonukleotidový polymorfismus * MeSH
• LDL-cholesterol krev   MeSH
• lidé MeSH
• PCSK9 inhibitory * MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 genetika   MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• anticholesteremika MeSH
• biologické markery MeSH
• inhibitory serinových proteinas MeSH
• LDL-cholesterol MeSH
• PCSK9 inhibitory * MeSH
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH

BACKGROUND AND OBJECTIVE: Non-persistence with secondary preventive measures, including medications such as statins, adversely affects the prospects of successful outcomes. This study was aimed at evaluating non-persistence with statin therapy in cohorts of young and elderly patients after a transient ischaemic attack (TIA) and identifying patient-associated characteristics that influence the risk for non-persistence. METHODS: The study cohorts included 797 adult patients who were initiated on statin therapy following a TIA diagnosis between 1 January 2010 and 31 December 2010. Patients were followed up for 3 years and those with a treatment gap of at least a 6-month period were considered 'non-persistent'. In order to identify any age-related differences, all analyses were conducted in the entire study cohort (n = 797) as well as separately in the 'younger' (aged <65 years, n = 267) and the 'older' (aged ≥65 years, n = 530) patients. RESULTS: Non-persistence was significantly more common in younger patients compared to older patients (67.8% vs. 49.1%; p < 0.001). Factors that decreased the probability of non-persistence in younger and older patients included diabetes mellitus (hazard ratio [HR] = 0.72 and HR = 0.64, respectively) and hypercholesterolaemia (HR = 0.43 and HR = 0.62, respectively). Female gender (HR = 1.42) was associated with a higher and increasing number of medications taken (HR = 0.93), with lower probability for non-persistence in younger patients but not in the older patients. CONCLUSIONS: Our results indicate that certain patients with TIA require special counselling to improve persistence with statin therapy. These include younger patients, especially females and those not on polypharmacy, and both younger and older patients without diabetes mellitus or hypercholesterolaemia.

• MeSH
• adherence k farmakoterapii * MeSH
• diabetes mellitus epidemiologie   MeSH
• hypercholesterolemie farmakoterapie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• polypharmacy MeSH
• proporcionální rizikové modely MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• statiny terapeutické užití   MeSH
• tranzitorní ischemická ataka farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• statiny MeSH

OBJECTIVE: Even though statin pretreatment is associated with better functional outcomes and lower risk of mortality in acute ischemic stroke, there are limited data evaluating this association in acute ischemic stroke due to large artery atherosclerosis (LAA), which carries the highest risk of early stroke recurrence. METHODS: Consecutive patients with acute LAA were prospectively evaluated from 7 tertiary-care stroke centers during a 3-year period. Statin pretreatment, demographics, vascular risk factors, and admission and discharge stroke severity were recorded. The outcome events of interest were neurologic improvement during hospitalization (quantified as the relative decrease in NIH Stroke Scale score at discharge in comparison to hospital admission), favorable functional outcome (FFO) (defined as modified Rankin Scale score of 0-1), recurrent stroke, and death at 1 month. Statistical analyses were performed using univariable and multivariable Cox regression models adjusting for potential confounders. All analyses were repeated following propensity score matching. RESULTS: Statin pretreatment was documented in 192 (37.2%) of 516 consecutive patients with LAA (mean age: 65 ± 13 years; 60.8% men; median NIH Stroke Scale score: 9 points, interquartile range: 5-18). Statin pretreatment was associated with greater neurologic improvement during hospitalization and higher rates of 30-day FFO in unmatched and matched (odds ratio for FFO: 2.44; 95% confidence interval [CI]: 1.07-5.53) analyses. It was also related to lower risk of 1-month mortality and stroke recurrence in unmatched and matched analyses (hazard ratio for recurrent stroke: 0.11, 95% CI: 0.02-0.46; hazard ratio for death: 0.24, 95% CI: 0.08-0.75). CONCLUSION: Statin pretreatment in patients with acute LAA appears to be associated with better early outcomes regarding neurologic improvement, disability, survival, and stroke recurrence.

• MeSH
• cévní mozková příhoda diagnóza   farmakoterapie   mortalita   MeSH
• hospitalizace trendy   MeSH
• intrakraniální arterioskleróza diagnóza   farmakoterapie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• následné studie MeSH
• prospektivní studie MeSH
• senioři MeSH
• statiny terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• statiny MeSH

Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term 'statin intolerance'. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10-15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented.

• Klíčová slova
• definition, muscle symptoms, risk factors, statin intolerance,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper.

• MeSH
• diabetes mellitus 2. typu genetika   MeSH
• genetické testování MeSH
• HDL-cholesterol metabolismus   MeSH
• hydroxymethylglutaryl-CoA-reduktasy genetika   MeSH
• index tělesné hmotnosti MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• LDL-cholesterol metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• senioři MeSH
• statiny škodlivé účinky   MeSH
• tělesná hmotnost genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• HDL-cholesterol MeSH
• HMGCR protein, human MeSH Prohlížeč
• hydroxymethylglutaryl-CoA-reduktasy MeSH
• LDL-cholesterol MeSH
• statiny MeSH

BACKGROUND AND PURPOSE: Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. METHODS: We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. RESULTS: In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). CONCLUSIONS: In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.

• Klíčová slova
• carotid stenosis, ischemic attack, transient, statin,
• MeSH
• časové faktory MeSH
• cévní mozková příhoda diagnostické zobrazování   patofyziologie   prevence a kontrola   MeSH
• difuzní magnetická rezonance metody   MeSH
• ischemie mozku diagnostické zobrazování   farmakoterapie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• radiografie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• statiny aplikace a dávkování   MeSH
• stenóza arteria carotis diagnostické zobrazování   farmakoterapie   patofyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• statiny MeSH