Use Of Lipid-lowering Drugs Research Articles

Statins and Renin Angiotensin System Inhibitors Dose-Dependently Protect Hypertensive Patients against Dialysis Risk.

BackgroundTaiwan has the highest renal disease incidence and prevalence in the world. We evaluated the association of statin and renin–angiotensin system inhibitor (RASI) use with dialysis risk in hypertensive patients.MethodsOf 248,797 patients who received a hypertension diagnosis in Taiwan during 2001–2012, our cohort contained 110,829 hypertensive patients: 44,764 who used RASIs alone; 7,606 who used statins alone; 27,836 who used both RASIs and statins; and 33,716 who used neither RASIs or statins. We adjusted for the following factors to reduce selection bias by using propensity scores (PSs): age; sex; comorbidities; urbanization level; monthly income; and use of nonstatin lipid-lowering drugs, metformin, aspirin, antihypertensives, diuretics, and beta and calcium channel blockers. The statin and RASI use index dates were considered the hypertension confirmation dates. To examine the dose–response relationship, we categorized only statin or RASI use into four groups in each cohort: <28 (nonusers), 28–90, 91–365, and >365 cumulative defined daily doses (cDDDs).ResultsIn the main model, PS-adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for dialysis risk were 0.57 (0.50–0.65), 0.72 (0.53–0.98), and 0.47 (0.41–0.54) in the only RASI, only statin, and RASI + statin users, respectively. RASIs dose-dependently reduced dialysis risk in most subgroups and in the main model. RASI use significantly reduced dialysis risk in most subgroups, regardless of comorbidities or other drug use (P < 0.001). Statins at >365 cDDDs protected hypertensive patients against dialysis risk in the main model (aHR = 0.62, 95% CI: 0.54–0.71), regardless of whether a high cDDD of RASIs, metformin, or aspirin was used.ConclusionStatins and RASIs independently have a significant dose-dependent protective effect against dialysis risk in hypertensive patients. The combination of statins and RASIs can additively protect hypertensive patients against dialysis risk.

A comparative study of medication use after stroke in four countries

ObjectivesThe use of medication plays an important role in secondary stroke prevention and treatment of post-stroke comorbidities. The Collaborative Evaluation of Rehabilitation in Stroke across Europe (CERISE) was set up to investigate the inpatient stroke rehabilitation process in four centres, each in a different European country: Belgium, Germany, United Kingdom and Switzerland. Patients and methodsPatients’ medication use 5 years post-stroke was compared between countries. Focus was put on cerebrovascular secondary prevention, including (a) adequate antithrombotic treatment, (b) treatment of cardiovascular comorbidities and diabetes, and (c) the use of lipid-lowering drugs; as well as on the treatment of stroke-related disorders such as depression, anxiety and pain. ResultsMedication data were available for 247 patients. Data about depression and anxiety were available for 233. ConclusionThere were no significant differences between the four centres in antithrombotic treatment and in the treatment of cardiovascular comorbidities and diabetes. However, significantly more patients from the UK were treated with lipid-lowering drugs compared to Belgian patients. Significant differences were also observed between the centres in the prevalence and treatment of depression. More Belgian patients suffered from depression compared to German patients and significantly more Belgian patients took antidepressants than patients in Germany. This was in contrast to the prevalence and treatment of anxiety and pain, for which no significant differences between the centres were seen. Related to pain treatment, it was observed that almost 40% of all patients suffering from pain, used no specific medication.

Major adverse cardiovascular events with basal insulin peglispro versus comparator insulins in patients with type 1 or type 2 diabetes: a meta-analysis.

BackgroundTo identify possible differences in cardiovascular (CV) risk among different insulin therapies, we performed pre-specified meta-analyses across the clinical program for basal insulin peglispro (BIL), in patients randomized to treatment with BIL or comparator insulin [glargine (IG) or NPH].MethodsOne phase 2 (12-week) and 6 phase 3 (26 to 78-week) randomized studies of BIL compared to IG or NPH, in patients with type 1 or type 2 diabetes, were included. The participants were diverse with respect to demographics, baseline glycemic control, and concomitant disease or medications, but treatment groups were comparable in each study. For any potential CV or neurovascular event, relevant medical information was provided to a blinded external clinical events committee (C5Research, Cleveland Clinic, Cleveland, OH, USA) for adjudication. Cox regression analysis was used to compare treatment groups. The primary endpoint was a composite of adjudicated MACE+ [CV death, myocardial infarction (MI), stroke, or hospitalization for unstable angina].ResultsThe pooled population included 5862 patients in the safety evaluation, with randomization to BIL:IG:NPH of 3578:2072:212. Mean age was 54.1 years, 27 % had type 1 diabetes, 56 % were male, and 88 % were white. Baseline demographic and clinical characteristics, including use of statins or other lipid-lowering drugs, were comparable between BIL and comparators. A total of 83 patients experienced at least 1 MACE+ and 70 patients experienced at least 1 MACE (CV death, MI, or stroke). Overall, there were no treatment-associated differences in time to MACE+ [hazard ratio (HR) for BIL versus comparator insulin (95 % CI): 0.82 (0.53–1.27)] or MACE [0.83 (0.51–1.33)]. In 4297 patients with type 2 diabetes, there were 71 MACE+ events [HR: 1.02 (95 % CI: 0.63–1.65), p = 0.94]. In 1565 patients with type 1 diabetes, there were only 12 MACE+ [0.24 (0.07–0.85), p = 0.027]. There were no differences in all-cause death between BIL and comparators. Sub-group analyses did not identify any sub-population with increased risk with BIL versus comparator insulins.ConclusionsTreatment with BIL versus comparator insulin in patients with type 1 diabetes or type 2 diabetes was not associated with increased risk for major CV events in the studies analyzed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0393-6) contains supplementary material, which is available to authorized users.

HIV Infection and Carotid Artery Intima-media Thickness: Pooled Analyses Across 5 Cohorts of the NHLBI HIV-CVD Collaborative.

Age and human immunodeficiency virus (HIV) treatment may affect the association of HIV infection with atherosclerosis. We used identical carotid artery B-mode ultrasonographic methods in 5 cohorts participating in the National Heart, Lung, and Blood Institute HIV-CVD Collaborative to measure intima-media thickness of the right far wall of the common carotid artery (CCA-IMT) and carotid artery bifurcation (BIF-IMT) between 2010 and 2013. Participants aged 6-75 years were either HIV infected or uninfected. Linear regression assessed associations of CCA-IMT and BIF-IMT with HIV infection and cardiovascular disease risk factors, within age and HIV treatment groups. Adjustment variables included sex, race/ethnicity, smoking, height, weight, and use of antihypertensive and lipid-lowering drugs. We studied 867 HIV-infected and 338 HIV-uninfected male and 696 HIV-infected and 246 HIV-uninfected female participants. Among both middle-aged (30-49 years) and older adults (50-75 years), HIV-infected participants had CCA-IMT and BIF-IMT values that were similar to or lower than those in HIV-uninfected participants. In contrast, among those aged 6-29 years, HIV infection was associated with higher CCA-IMT and BIF-IMT values. Among HIV-infected participants, associations of higher systolic blood pressure and lower high-density lipoprotein cholesterol with Carotid artery intima-media thickness strengthened with age. The effects of HIV on carotid artery structure may differ across the lifespan, with traditional determinants of cardiovascular disease burden playing a larger role and HIV playing a lesser role in older adults than in young adults and children.

Lipids--Diagnosis and therapy in diabetes mellitus

Hyper- and dyslipidemia contribute to cardiovascular morbidity and mortality in diabetic patients. Pharmacological therapy to lower LDL cholesterol has convincingly shown to reduce cardiovascular risk in diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the use of lipid-lowering drugs in diabetic patients according to current scientific evidence.

Dyslipidemias and statins: from guidelines to clinical practice. An updated review of the literature

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability not only in countries with a high degree of socio-economic development but also in low-middle income countries. The study of atherosclerosis and the strategies to control ASCVD are in progress. All strategies emphasize the need for lowering LDL cholesterol through appropriate lifestyle and use of lipid-lowering drugs, mainly statins. The mode of approach is variable. Statin therapy is recommended in secondary prevention, whereas use in primary prevention is still a matter of debate. The guidelines provided by international panels serve as a reference in clinical practice but, as stated by the National Cholesterol Education Program (NCEP), do not replace the physician's clinical judgment.

Clinical and laboratory data of a large series of patients with congenital generalized lipodystrophy.

BackgroundBerardinelli-Seip congenital lipodystrophy (BSCL) was initially described by Berardinelli in Brazil in 1954 and 5 years later by Seip in Norway. It is an autosomal recessive disease that leads to a generalized deficit of body fat, evolving with diabetes and hypertriglyceridemia. The aim of this study was to describe the clinical and laboratory characteristics of a large series of patients with BSCL.MethodsThis is a cross-sectional study of patients with BSCL. A total of 54 cases of BSCL were diagnosed, treated and followed for the past 17 years. We report clinical and laboratorial data of 44 of those patients.ResultsThere was a predominance of female patients (27 patients), and the mean age was 21.3 ± 13.7 years old. The majority of patients (30/44; 68.2 %) were diabetic, and almost half of them (14/30 patients, 46.7 %) were on insulin. The mean body mass index was 19.6 ± 3.3 and the mean body fat measured by dual-energy X-ray absorptiometry (DEXA) was 5.4 ± 0.8 %. Acanthosis nigricans, acromegaloid facies, atrophic cheeks, prognathism, phlebomegaly, and muscle hypertrophy were the most common clinical features. Only two patients had triglyceridemia lower than 150 mg/dl without the use of lipid-lowering drugs. Hyperinsulinemia was present in the majority of patients, and leptin values were very low in all patients.ConclusionsWe report one of the largest series of patients with BSCL treated at a single medical center. Earlier identification of the mutations and a better understanding of the pathophysiology can aid to better treatment and decrease complications, potentially improving life quality and expectancy.

Greater decreases in cholesterol levels among individuals with high cardiovascular risk than among the general population: the northern Sweden MONICA study 1994 to 2014.

AimDecreasing cholesterol levels in Western populations is the main reason for decreasing mortality due to coronary heart disease. Our aim was to analyze trends in cholesterol levels in the population during a period of 20 years in relation to previous cardiovascular disease (CVD), other cardiovascular risk factors, and socioeconomic status.Methods and resultsA total of 4546 women and 4349 men aged 25–74 years participated in five population-based surveys in the Northern Sweden MONICA Study between 1994 and 2014 (participation rate 76.8–62.5%). Total cholesterol levels decreased from 6.2 mmol/L (95% confidence interval, CI, 6.1–6.2) in 1994 to 5.5 mmol/L (CI 5.4–5.5) in 2014. The decrease was more pronounced in elderly vs. younger participants (1.0 vs. 0.5 mmol/L). In 2014, participants with previous CVD, diabetes, or hypertension had lower cholesterol levels than the general population, whereas their levels were higher or similar to the general population in 1994. The use of lipid-lowering drugs increased markedly and was used by 14.3% in 2014. Previously described differences in cholesterol levels between participants with obesity and normal weight, and between those with and without university education, diminished, or vanished over time.ConclusionCholesterol levels decreased by 0.7 mmol/L over 20 years with no sign of abating. The improvement occurred in all age and gender groups but more prominently among those at high risk of ischaemic heart disease.

Abstract P269: Circulating Fatty Acids, Determinants and Use as Biomarkers for Dietary Intake: The CoDAM and Hoorn Study

Objective: To increase the understanding of circulating fatty acids (FA) as biomarkers of FA intake, we investigated (1) determinants of circulating proportions of linoleic acid (LA), alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA); and (2) the effect of demographic, lifestyle, and health factors on the relation between circulating and self-reported intake of LA, ALA, EPA, and DHA. Hypothesis: We hypothesized that demographic, lifestyle, and health factors influence the relation between circulating and self-reported intake of FA. Methods: Cross-sectional analysis in combined data from the CoDAM (n=472) and Hoorn study (n=708). Dietary FA intakes (% of total FA) were calculated from a validated 79-item semi-quantitative food frequency questionnaire. Fasting total fatty acids (% of total FA) in plasma (CoDAM) or serum (Hoorn) were measured by gas liquid chromatography. The variation in circulating proportions of FA explained by demographic, lifestyle and health factors was calculated by multivariable linear regression analysis. Correlation coefficients between circulating proportions of FA and self-reported FA intakes were calculated by standardized multivariable linear regression analysis adjusted for demographic, lifestyle, and health factors. To assess the influence of specific factors on correlations, stratified analyses were performed and interactions were calculated. Results: Self-reported intakes were the primary determinants of circulating proportions of LA (partial R2: 7%), ALA (2%), EPA (9%) and DHA (16%). Standardized regression coefficients between circulating and self-reported FA were: LA β=0.280 (95% Confidence Interval: 0.227-0.333), ALA β=0.130 (0.071-0.188), EPA β=0.338 (0.281-0.395), and DHA β=0.450 (0.397-0.503). Other determinants of circulating FA were the use of lipid lowering drugs, waist circumference and sex for LA; prevalence of type 2 diabetes mellitus, age, sex, and alcohol intake for EPA; and age for DHA. The correlation between circulating and dietary LA was stronger among people with a lower vs higher waist circumference and higher vs lower alcohol intake (interaction: p&lt;0.05). In women, the correlation between circulating and dietary EPA and DHA was weaker than in men, and the correlation between circulating and dietary DHA was higher with higher alcohol intake. Underreporting of energy intake did not affect the correlations. Conclusion: Self-reported intake of FA is the primary, but not the only determinant of circulating proportions of LA, ALA, EPA and DHA. This analysis indicates that demographic, lifestyle, and health characteristics may influence the relation between circulating proportions and self-reported intake of FA. Improved understanding is needed of factors determining circulating FA and the implication for their use as biomarkers of dietary intake in different subgroups.

Abstract P102: Longitudinal and Secular Decrease in Total Cholesterol Levels in All Birth Cohorts. The Tromsø Study 1979-2008

Introduction: Elevated blood cholesterol is a modifiable risk factor for cardiovascular disease (CVD). Surveillance of cholesterol levels is needed to study disease burden, consider priorities for CVD prevention and intervention, and understand the effect of diet, lifestyle and medication use. Previous studies show a cholesterol level decline in recent decades, but lack data to follow individuals from different birth cohorts from early and middle adulthood to older age. Hypothesis: To assess secular and longitudinal trends in total cholesterol levels. Methods: We investigated changes in age-specific cholesterol levels by repeated measurements in 37,968 women and men born 1905-1977 examined up to five times between 1979 and 2008 in the population-based Tromsø Study. Results: Mean total cholesterol decreased from 1979 to 2008 in both genders in all age groups. The decrease in age group 40-49 years was 1.2 mmol/l in women and 1.0 mmol/l in men. Both the 80th percentile and the 20th percentile of the population cholesterol distribution decreased. In birth cohorts born 1940-77, mean total cholesterol levels increased with age up to 2001 and decreased thereafter to 2007. Among those born 1910-39, the cholesterol decrease was evident after 1994-95. The longitudinal trends in those born 1940-77 were not influenced by use of lipid-lowering drugs, while the decrease with age in birth cohorts born 1910-39 was slightly weaker among never users of lipid-lowering drugs compared to the total sample. Conclusions: A longitudinal decrease in mean cholesterol levels was observed from 1994-95 or from 2001 depending on birth cohort. A secular decrease was observed from 1979-80 in all age groups. The findings points to a mass population effect rather than a treatment effect of high-risk individuals alone.

Mediating effect of insulin related indices on the association between body fat with blood pressure among overweight adults

To examine the contribution of insulin related indices on the association between body fat and blood pressure among overweight adults. From April to May 2014, based on convenience sampling, we recruited overweight and obese volunteer participants aged 20-55 years living in Beijing at least 1 year through a strict examination by doctors in a physical examination center. In this study, we excluded the participants who reported suffering from any severe heart, lung, liver or kidney organic diseases, and abnormal development, disabilities, and secondary obesity caused by other disease. Also participants with use of antihypertensive drugs, hypoglycemic drugs and lipid lowering drugs were excluded for this study. A total of 1 221 participants were investigated in this study. With a simple self-designed questionnaire, the birthdates, sex, drug use, and disease history were examined. Participants' blood pressure (BP), percentage of body fat (PBF), glucose and fasting insulin level were measured. Mediation analysis was used to analyze the total effect of PBF on BP (c), the association between PBF and insulin related indices (a), and the mediation effect of serum fasting insulin level/HOMA-IR/HOMA-%S on relation between PBF and systolic/diastolic blood pressure (SBP/DBP). PBF was positively associated with SBP (c=0.25 ± 0.05 and 0.19 ± 0.03 for male and female, respectively, P<0.001). In males, PBF was positively associated with fasting insulin level and HOMA-IR (a=0.28 ± 0.05 and 0.24 ± 0.05, P<0.001), and negatively associated with HOMA-%S (a=-0.29 ± 0.05, P<0.001); in females, PBF was positively associated with fasting insulin level, HOMA-IR (a=0.21 ± 0.04 and 0.20 ± 0.04, P<0.001), and negatively associated with HOMA-%S (a=-0.13 ± 0.04, P<0.001). In further mediation analysis for female participants, fasting insulin level/HOMA-IR/HOMA-%S played mediation roles in the relation between PBF and SBP, with ratio of mediation of 13.78%,18.3%, and 5.98%. Fasting insulin level/HOMA-IR also mediated the relation between PBF and DBP, with mediation ratio of 11.98% and 14.13%. In overweight/obese female participants, insulin related indices mediated the relation between PBF and BP.

Three Years After Bariatric Surgery in Obese Adolescents

Research Article| February 01 2016 Three Years After Bariatric Surgery in Obese Adolescents AAP Grand Rounds (2016) 35 (2): 17. https://doi.org/10.1542/gr.35-2-17 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Three Years After Bariatric Surgery in Obese Adolescents. AAP Grand Rounds February 2016; 35 (2): 17. https://doi.org/10.1542/gr.35-2-17 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: bariatric surgery, obesity, obesity, morbid Source: Inge TH, Courcoulas AP, Todd MJ, et al. Weight loss and health status 3 years after bariatric surgery in adolescents [published online ahead of print November 6, 2015]. N Engl J Med. doi: https://doi.org/10.1056/NEJMoa1506699 Investigators at 5 pediatric tertiary care centers in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Consortium conducted a prospective study to determine the effects of bariatric surgery in obese adolescents. For the study, adolescents (≤19 years old) who underwent the procedure from 2007 through 2012 were enrolled. Standardized methods were used for data collection at baseline and at the 6-month and 1-, 2-, and 3-year postoperative visits. Data were collected on weight loss, coexisting conditions, weight-related quality of life, and micronutrient levels. Quality of life was measured using the total score on the Weight on Quality of Life-Kids instrument (scores range from 0–100). Information on surgical and endoscopic procedures performed between 31 days and 3 years after the bariatric surgery was also collected. Among the 242 study participants, Roux-en-Y gastric bypass was performed in 161, sleeve gastrectomy in 67, and adjustable gastric banding in 14. Because of the small size of the gastric band cohort their results were not included in the main analysis. At baseline, 29% of participants were 13–15 years old, 41% were 16–17 years old, and 30% were 18–19 years old. At baseline, the mean BMI was 53 (range 34–88) and 98% of participants had a BMI >40. Throughout the study interval, 99% (225/228) of the cohort actively participated and 88% (805/912) completed all of the postoperative visits. At 3-year follow-up, mean weight reduction was 41 kg with a mean 27% weight loss; 26% of the participants were no longer categorized as obese. However, 2% of the cohort who underwent gastric bypass and 4% of those who underwent sleeve gastrectomy exceeded their baseline weight. Compared to baseline, there was significant improvement in comorbidities in study participants by the 3-year follow-up. Hypertension was present in 96 participants at baseline, and normalized in 74% (71/94) of those at 3 years. New-onset hypertension developed in 4 participants. Dyslipidemia was present in 171 participants at baseline and normalized in 66% (112/171) without the use of lipid-lowering drugs. Incident dyslipidemia developed in 3 participants during the study interval. At baseline, 13% (29/233) of participants had type 2 diabetes (mean HgA1C = 6.3%), and at 3 years 19 of 20 participants on whom data were available were in remission. Newonset pre-diabetes developed in 1 participant. The mean quality-of-life score was 63 at baseline and increased to 83 by 3 years (P < .001). Micronutrient deficiencies either continued or worsened over the 3-year study period, including low ferritin levels, low B12 levels, vitamin A deficiency, and vitamin D deficiency. Within 3 postoperative years, 44 additional intra-abdominal surgical procedures related to the bariatric surgery were performed on 30 patients. In addition, upper endoscopic procedures were performed in 29 participants. The authors conclude that the majority of adolescents who had bariatric surgery experienced... You do not currently have access to this content.

Abstract WP320: The Management of low Density Lipid Cholesterol and Predictors of Goal Achievement in Stroke Patients in China

Background and Purpose: Modification of low-density lipoprotein cholesterol (LDL-C) has been proved to be an essential component in the primary and secondary prevention of stroke. However, limited data are available on LDL-C goal achievement in patients with ischemic stroke in China. The aim of this study was to assess the management of low-density lipoprotein cholesterol (LDL-C) in patients suffering from ischemic stroke within 6-12 months and to explore the predictors of the achievement of LDL-C target. Method: This study was a nation-wide, multicenter, cross-sectional study conducted from July 2013 to August 2013. Patients who had an ischemic stroke within 6-12 months and were more than 18-year old were included into this study. All data referred to personal information, medical history, medication and laboratory tests were collected by face-to-face questionnaires, physical examination and blood tests. The predictors for the achievement of LDL-C target (&lt;1.8mmol/l or &lt;70mg/dl) were analyzed by the multivariate analysis. Results: In this study, a total of 3956 cases from 56 centers suffered from ischemic stroke within 6-12 months were finally included into this study. The average serum level of LDL-C in all these patients was 2.42 ± 0.91mmol/l with the median of 2.30 mmol/l and the total LDL-C goal achievement rate is 27.35% (95% CI: 25.97%-28.77%). Lipid-lowering therapy (Odds Ratio [OR]=3.045, 95%CI: 2.456-3.810) was the most significant predictor for LDL-C target achievement and female (OR=0.684, 95% CI: 0.540-0.867), current smoking (OR=0.627, 95% CI: 0.480-0.817), and history of dyslipidemia (OR=0.592, 95% CI: 0.497-0.704) were three other important factors for the LDL-C goal achievement. Conclusions: Although the lipid modulation in stroke patients is recommended by the international guidelines, the goal achievement of LDL-C was still very low in this population in China. The modifiable predictors including the use of lipid-lowering drugs and smoking cessation should be improved in dyslipidemia management.

Dyslipidemia Part 2: Review of Dyslipidemia Treatment in Patients With Noncoronary Vascular Disease.

Dyslipidemia is one of the major modifiable risk factors associated with atherosclerotic cardiovascular disease. Appropriate modification of lipid profiles reduces the progression of atherosclerosis in vessel walls across all vascular beds. The management of dyslipidemia has evolved over the last several decades, especially since the discovery of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, also known as statins. Statin use in atherosclerotic heart disease is well described in observational and prospective placebo-controlled studies, citing both lipid-lowering and pleiotropic effects. However, the effect of statins and other lipid-lowering agents on noncoronary arterial beds (the aorta, arteries to the extremities, renal, and carotid arteries) is less understood. This article is part 2 of a 2-part review, with part 1 having focused on lipid metabolism and the downstream effects of lipids on the development of atherosclerosis. The current review (part 2) will discuss trials, retrospective reviews, and observational cohort studies regarding the use of statins and/or other lipid-lowering drugs for primary and secondary prevention of peripheral noncoronary atherosclerotic disease.

Higher Levels of Cystatin C Are Associated with Extracranial Carotid Artery Steno-Occlusive Disease in Patients with Noncardioembolic Ischemic Stroke

Background: Large artery atherosclerosis is a major cause of ischemic stroke worldwide. Differential biomarker profiles associated with extra- and intracranial atherosclerosis are a topic of considerable interest. Cystatin C (CysC), a marker of renal function, is a risk factor for cardiovascular disease. Aim: We sought to determine whether CysC levels were associated with extra- and intracranial large artery stenosis (LAS) in patients with acute ischemic stroke. Methods: We retrospectively analyzed data of acute noncardioembolic ischemic stroke patients who were admitted to our stroke center within 5 days from symptom onset. Serum CysC levels were measured using latex agglutination turbidimetric immunoassay. Extra- and intracranial LAS were defined as ≥50% diameter stenosis or occlusion of the relevant internal carotid artery (ICA) and/or middle cerebral artery (MCA) using carotid echography and volume rendering on magnetic resonance angiography. Multivariate logistic analyses were used to assess the association between CysC levels and LAS after adjustment for potential confounders. Results: Of 205 patients (mean age 70.2 years), 76 (37.1%) had LAS. The distribution of LAS was 29 extracranial ICA, 34 intracranial ICA/MCA (8 ICA only, 25 MCA only, 1 ICA+MCA) and 13 tandem stenosis (both extracranial ICA and intracranial ICA/MCA). Levels of CysC were higher in patients with extracranial ICA stenosis than in those with intracranial ICA/MCA stenosis (1.23 ± 0.33 vs. 0.97 ± 0.21 mg/l, p < 0.001). In multivariate analysis, the highest CysC tertile (>1.04 mg/l) was significantly associated with extracranial ICA stenosis (adjusted odds ratio [OR] 5.01, 95% confidence interval [CI] 1.51-16.63, p = 0.009) after adjustment for age, sex, diabetes, chronic kidney disease, current smoking, systolic blood pressure, HDL cholesterol, high-sensitivity C-reactive protein (hs-CRP) and premorbid lipid-lowering drugs use. When CysC was considered as a continuous variable, 1 SD increase in CysC was significantly associated with extracranial ICA stenosis (adjusted OR 3.01, 95% CI 1.58-5.72, p = 0.001). However, there were no significant associations between CysC levels and intracranial ICA/MCA stenosis. In addition, CysC levels showed a weak but statistically significant correlation with hs-CRP levels (r = 0.195, p = 0.021). Using receiver operating characteristic curve analysis, CysC value displayed good performance in discriminating extracranial ICA stenosis (c-statistic 0.79, 95% CI 0.69-0.89, p < 0.001). Conclusions: This preliminary study suggests that higher levels of CysC were independently associated with symptomatic extracranial ICA stenosis, but not with intracranial ICA/MCA stenosis in patients with noncardioembolic stroke. Our findings provide new insights into the link between serum CysC and carotid atherosclerosis.

Suboptimal Control of Lipid Levels: Results from 29 Countries Participating in the Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS).

Five multicentre, cross-sectional Centralized Pan-Regional Surveys on the Undertreatment of Hypercholesterolaemia (CEPHEUS) were conducted in 29 countries across Asia, Western Europe, Eastern Europe, the Middle East, and Africa. The surveys assessed the current use and efficacy of lipid-lowering drugs (LLDs) worldwide and identified possible patient and physician characteristics associated with failure to attain low-density lipoprotein cholesterol (LDL-C) goals. The aim of this analysis was to consolidate the global results from these surveys. The surveys involved patients aged ≥18 years who had been prescribed LLDs for at least 3 months without dose changes for at least 6 weeks. A single visit was scheduled for data collection, including fasting plasma lipid and glucose levels. Cardiovascular risk profile and LDL-C goal attainment were assessed according to the 2004 updated US National Cholesterol Education Program Adult Treatment Panel III guidelines. In total, 35 121 patients (mean age: 60.4 years) were included, and 90.3% had been prescribed statin monotherapy. Overall, only 49.4% of patients reached their recommended LDL-C level. LDL-C goals were attained in 54.8% (5084/9273) and 22.8% (3287/14 429) of patients were at high and very high cardiovascular risk, respectively. Factors associated with an increased likelihood of LDL-C goal attainment were lower baseline cardiovascular risk; presence of diabetes mellitus, hypertension, or history of cardiovascular disease; and treatment with simvastatin, atorvastatin, or rosuvastatin (vs. all other LLDs). LDL-C goal attainment in patients taking LLDs is suboptimal worldwide, particularly in patients at high and very high cardiovascular risk.

The effect of bergamot on dyslipidemia

BackgroundStatins are the most common used lipid lowering drugs but they may cause adverse effects and despite their well-established therapeutic benefits residual cardiovascular (CV) risk remains. The use of other lipid lowering drugs and nutraceuticals alone or as add-on lipid-modifying therapy can be an option in such cases. Several studies have reported health-related properties of the Citrus fruits, among which bergamot (Citrus bergamia Risso) differs from others by particularly high content of certain compounds. PurposeThis narrative review summarizes the current evidence on the effects of bergamot on lipid parameters based on studies involving animals and humans. Main evidenceThis natural supplement may lead to effective lipid-lowering treatment. Its lipid-lowering activity is attributed to different flavonoids. However, the exact mechanisms involved remain unclear. ConclusionIt is expected that ongoing and future studies will confirm the benefit of bergamot in dyslipidemic and other cardiometabolic disorders, potentially leading to reduced overall CV risk.

Circulating Lipoprotein Concentrations Correlate with Total but Not Free Heme in Different Sickle Cell Disease Genotypes

In chronic hemolytic states, hemoglobin is released in the bloodstream and free heme is formed upon hemoglobin oxidation. Free heme has been shown to trigger vaso-occlusion in animal models of sickle cell disease (SCD) by activating endothelial cells through toll-like receptor 4 (TLR4). Serum levels of glycoproteins specialized in clearing hemoglobin and heme, such as haptoglobin and hemopexin, are typically depleted in SCD plasma. High-density (HDL) and low-density lipoproteins (LDL) can also bind heme and work as the first line of defense against heme toxicity. Heme can react with LDL and generate oxidized LDL (ox-LDL), another TLR4 ligand.We aimed to investigate the importance of lipoproteins as heme scavengers by comparing SCD patients with homozygous sickle cell anemia (SS) patients and double heterozygous hemoglobin SC disease (SC) patients, who present with higher and lower hemolytic rates, respectively.Eighty-three patients (aged 18-68 years old, 44 female) participated in this study: 43 SS (12 receiving hydroxyurea - HU) and 40 SC. Exclusion criteria were pregnancy, blood transfusion, pain crisis, or use of lipid lowering drugs in the past 3 months. Peripheral venous blood samples were collected in tubes with EDTA for complete blood counts and without antiocoagulant for serum separation after centrifugation at 500g for 20 min. Serum lactate dehydrogenase, total cholesterol and HDL were measured by conventional enzymatic-colorimetric methods on a Roche Hitachi Modular automation system (Roche, Germany). LDL was calculated by Friedewald equation. Serum oxidized LDL (ox-LDL), total and free heme were determined with commercially available ELISA assays (Mercodia Oxidized LDL ELISA, Heme QuantiChrom Assay, Bioassay Systems, USA). Statistical analysis was performed with SPSS v.22.0.LDH and reticulocyte count were significantly higher in SS patients than SC, and hemoglobin was significantly lower (P =0.001). Total heme was significantly higher in SS patients taking HU (SSHU) (90 ± 59 mM) compared with SC patients (66 ± 18 mM), P =0.01. Total cholesterol was higher in SC than in SS patients, 141 ± 28 vs. 107 ± 20 mg/dL, respectively, P =0.01). We found no significant differences between groups regarding LDL (P =0.08), HDL (P =0.10), ox-LDL (P =0.52). Total heme correlated negatively with total cholesterol (r=-0.33, P =0.037) and HDL (r=-0.49, P =0.001) in the whole population, regardless of genotype or treatment with HU. Surprisingly, free heme did not differ between SS, SSHU, or SC groups of patients (P=0.19), and did not correlate with cholesterol levels.The negative correlation between total heme and total cholesterol supports that lipoproteins contribute to defend the body against heme toxicity. Despite HDL, LDL, and ox-LDL not being significantly different among the groups, the stronger negative correlation between total heme and HDL suggests that this cholesterol fraction may be more important in heme scavenging. We hypothesize that more intense hemolysis may lead to the production of heme capable of oxidizing lipoproteins, which can then be rapidly cleared by macrophages, explaining hypocholesterolemia in SS patients. Similar concentrations of free heme and ox-LDL in all groups suggests that, in steady state, their concentrations are kept relatively constant regardless of hemolytic rate. Since circulating concentrations of these TLR4 ligands did not differ between SC and SS patients in our study, this might indicate that the contribution of hemolysis to endothelial dysfunction and to differences in severity and in the variety of complications between these genotypes may be better explained by TLR4 activation by bound heme rather than by activation by free heme or ox-LDL.Financial support: FAPESP/CAPES/CNPq DisclosuresNo relevant conflicts of interest to declare.

Nitrated apolipoprotein AI/apolipoprotein AI ratio is increased in diabetic patients with coronary artery disease

Aims/hypothesisRecent studies have suggested that determination of HDL function may be more informative than its concentration in predicting its protective role in coronary artery disease (CAD). Apolipoprotein AI (apoAI), the major protein of HDL, is nitrosylated in vivo to nitrated apoAI (NT-apoAI) that might cause dysfunction. We hypothesized that NT-apoAI/apoAI ratio might be associated with diabetes mellitus (DM) in CAD patients. MethodsWe measured plasma NT-apoAI and apoAI levels in 777 patients with coronary artery disease (CAD) by ELISA. Further, we measured plasma cholesterol efflux potential in subjects with similar apoAI but different NT-apoAI levels. ResultsWe found that median NT-apoAI/apoAI ratio was significantly higher in diabetes mellitus (DM) (n = 327) versus non-diabetic patients (n = 450). Further analysis indicated that DM, thiobarbituric acid-reactive substances and C-reactive protein levels were independent predictors of higher NT-apoAI/apoAI ratio. There was negative correlation between NT-apoAI/apoAI and use of anti-platelet and lipid lowering drugs. The cholesterol efflux capacity of plasma from 67 individuals with differing NT-apoAI but similar apoAI levels from macrophages in vitro was negatively correlated with NT-apoAI/apoAI ratio. ConclusionsHigher NT-apoAI/apoAI ratio is significantly associated with DM in this relatively large German cohort with CAD and may contribute to associated complications by reducing cholesterol efflux capacity.

Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review

BackgroundTendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol.ObjectiveTo determine whether...