scholarly journals Lipoprotein Particle Predictors of Arterial Stiffness after 17 Years of Follow Up: The Malmö Diet and Cancer Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jacob Hartz ◽  
Ronald M. Krauss ◽  
Mikael Göttsater ◽  
Olle Melander ◽  
Peter Nilsson ◽  
...  

Background. Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. Methods. Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. Results. The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. Conclusions. The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.

2011 ◽  
Vol 19 (4) ◽  
pp. 781-794 ◽  
Author(s):  
Jeong Euy Park ◽  
Chern-En Chiang ◽  
Muhammad Munawar ◽  
Gia Khai Pham ◽  
Apichard Sukonthasarn ◽  
...  

Background: Treatment of hypercholesterolaemia in Asia is rarely evaluated on a large scale, and data on treatment outcome are scarce. The Pan-Asian CEPHEUS study aimed to assess low-density lipoprotein cholesterol (LDL-C) goal attainment among patients on lipid-lowering therapy. Methods: This survey was conducted in eight Asian countries. Hypercholesterolaemic patients aged ≥18 years who had been on lipid-lowering treatment for ≥3 months (stable medication for ≥6 weeks) were recruited, and lipid concentrations were measured. Demographic and other clinically relevant information were collected, and the cardiovascular risk of each patient was determined. Definitions and criteria set by the updated 2004 National Cholesterol Education Program guidelines were applied. Results: In this survey, 501 physicians enrolled 8064 patients, of whom 7281 were included in the final analysis. The mean age was 61.0 years, 44.4% were female, and 85.1% were on statin monotherapy. LDL-C goal attainment was reported in 49.1% of patients overall, including 51.2% of primary and 48.7% of secondary prevention patients, and 36.6% of patients with familial hypercholesterolaemia. The LDL-C goal was attained in 75.4% of moderate risk, 55.4% of high risk, and only 34.9% of very high-risk patients. Goal attainment was directly related to age and inversely related to cardiovascular risk and baseline LDL-C. Conclusion: A large proportion of Asian hypercholesterolaemic patients on lipid-lowering drugs are not at recommended LDL-C levels and remain at risk for cardiovascular disease. Given the proven efficacy of lipid-lowering drugs in the reduction of LDL-C, there is room for further optimization of treatments to maximize benefits and improve outcomes.


BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e019041 ◽  
Author(s):  
Farshid Hajati ◽  
Evan Atlantis ◽  
Katy J L Bell ◽  
Federico Girosi

ObjectivesWe examine the extent to which the adult Australian population on lipid-lowering medications receives the level of high-density lipoprotein cholesterol (HDL-C) testing recommended by national guidelines.DataWe analysed records from 7 years (2008–2014) of the 10% publicly available sample of deidentified, individual level, linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) electronic databases of Australia.MethodsThe PBS data were used to identify individuals on stable prescriptions of lipid-lowering treatment. The MBS data were used to estimate the annual frequency of HDL-C testing. We developed a methodology to address the issue of ‘episode coning’ in the MBS data, which causes an undercounting of pathology tests. We used a published figure on the proportion of unreported HDL-C tests to correct for the undercounting and estimate the probability that an HDL-C test was performed. We judged appropriateness of testing frequency by comparing the HDL-C testing rate to guidelines’ recommendations of annual testing for people at high risk for cardiovascular disease.ResultsWe estimated that approximately 49% of the population on stable lipid-lowering treatment did not receive any HDL-C test in a given year. We also found that approximately 19% of the same population received two or more HDL-C tests within the year. These levels of underutilisation and overutilisation have been changing at an average rate of 2% and −4% a year, respectively, since 2009. The yearly expenditure associated with test overutilisation was approximately $A4.3 million during the study period, while the cost averted because of test underutilisation was approximately $A11.3 million a year.ConclusionsWe found that approximately half of Australians on stable lipid-lowering treatment may be having fewer HDL-C testing than recommended by national guidelines, while nearly one-fifth are having more tests than recommended.


2020 ◽  
pp. bmjebm-2020-111413
Author(s):  
Robert DuBroff ◽  
Aseem Malhotra ◽  
Michel de Lorgeril

Drug treatment to reduce cholesterol to new target levels is now recommended in four moderate- to high-risk patient populations: patients who have already sustained a cardiovascular event, adult diabetic patients, individuals with low density lipoprotein cholesterol levels ≥190 mg/dL and individuals with an estimated 10-year cardiovascular risk ≥7.5%. Achieving these cholesterol target levels did not confer any additional benefit in a systematic review of 35 randomised controlled trials. Recommending cholesterol lowering treatment based on estimated cardiovascular risk fails to identify many high-risk patients and may lead to unnecessary treatment of low-risk individuals. The negative results of numerous cholesterol lowering randomised controlled trials call into question the validity of using low density lipoprotein cholesterol as a surrogate target for the prevention of cardiovascular disease.


2018 ◽  
Vol 40 (33) ◽  
pp. 2775-2781 ◽  
Author(s):  
Lotte C A Stiekema ◽  
Erik S G Stroes ◽  
Simone L Verweij ◽  
Helina Kassahun ◽  
Lisa Chen ◽  
...  

AbstractAimsSubjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a).Methods and resultsIn this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)]: age 60.0 [54.0–67.0] years, Lp(a) 200.0 [155.5–301.5] nmol/L [80.0 (62.5–121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8–55.5] and Lp(a) by 13.9% (95% CI 19.3–8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0–268.0) nmol/L [75.2 (56.0–107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (−8.3%) vs. placebo (−5.3%) [treatment difference −3.0% (95% CI −7.4% to 1.4%); P = 0.18].ConclusionEvolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.


2012 ◽  
Vol 11 (4) ◽  
pp. 70-78 ◽  
Author(s):  
R. G. Oganov ◽  
V. V. Kukharchuk ◽  
G. P. Arutyunov ◽  
A. S. Galyavich ◽  
V. S. Gurevich ◽  
...  

The high prevalence of persistent dyslipidemia in primary and specialized care patients treated with statins justifies the need to identify its reasons and develop the recommendations on the treatment optimization. At present, Russian studies focusing on the achievement of target lipid levels remain scarce, which emphasizes the importance of the problem and its further investigation.Aim.Cross-sectional epidemiological study which assessed the prevalence of persistent dyslipidemia in statin-treated patients and analysed the predictors of the achievement of target lipid levels.Material and methods.The lipid profile parameters were analysed in 1586 statin-treated out-patients with varied levels of cardiovascular risk, taking into account the type of lipid-lowering therapy and its doses. The assessment of the cardiovascular event (CVE) risk and the definition of target levels of low-density lipoprotein cholesterol (LDL–CH), as well as normal levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL–CH), was based on the clinical recommendations by the European Society of Cardiology (ESC 2007) and by the European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS 2011).Results.The analysis based on the ESC 2007 recommendations has demonstrated that the target levels of LDL–CH (<2,5 mmol/l for high-risk patients) were not achieved in 53,5% of the participants. The elevation of LDL–CH levels could be isolated or combined with the HDL–CH decrease and/or the TG increase. Low levels of HDL–CH were observed in 32,3% of the patients, while high TG levels were registered in 55,6% of the participants. The achievement of target LDL–CH levels was predicted by the higher-dose statin therapy (odds ratio 0,44). The analysis based on the ESC/EAS 2011 recommendations has shown that the prevalence of target LDL–CH levels was 12,2% in very high-risk patients (<1,8 mmol/l), 30,3% in high-risk patients (<2,5 mmol/l), and 53,4% in moderate-risk patients (<3,0 mol/l).Conclusion.Over a half of the statin-treated patients failed to achieve target levels of LDL–CH. The lowest prevalence of target LDL–CH levels was observed in very high-risk and high-risk patients. The predictors of target LDL–CH level achievement included moderate cardiovascular risk and higher-dose statin therapy. The obtained results suggest that the correction of persistent dyslipidemia in statin-treated patients could be achieved via increasing the satin dose and combining lipid-lowering medications.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Zhen Li ◽  
Qi Huang ◽  
Li Sun ◽  
Tengfei Bao ◽  
Zhe Dai

Objective. This study was designed to investigate risk factors related to atherogenic index of plasma (AIP), as well as the relationship between AIP and chronic microvascular complications in patients with type 2 diabetes (T2DM). Methods. This study included 2523 patients with T2DM who had not been treated with lipid-lowering drugs and were admitted to the Department of Endocrinology at Zhongnan Hospital, Wuhan University, during the period from January 2015 to February 2018. Anthropometric indicators were measured after overnight fasting. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) were detected by enzymatic analysis. Standard 75 g oral glucose tolerance testing was performed to measure 0 and 2 hr plasma levels of glucose and insulin. Insulin sensitivity was assessed with HOMA-IR. Results. Increase in AIP was associated with an increased risk for hypertension (P<0.05), HbA1c (P<0.05), HOMA-IR (P<0.05), UA (P<0.05), and decreased eGFR levels (P<0.05). Furthermore, AIP values directly correlated with BMI (r=0.182, P<0.001), waist circumference (r=0.129, P<0.001), blood glucose index (FBG (r=0.153, P<0.001), PPBG (r=0.117, P<0.001), and HbA1c (r=0.074, P<0.001)), insulin resistance (HOMA-IR; r=0.112, P<0.001), and uric acid (UA, r=0.177, P<0.001). Multiple logistic regression analysis showed that waist circumference, HOMA-IR, FBG, systolic blood pressure, and UA were independent risk factors for AIP (all P<0.05). The prevalence of diabetic neuropathy and metabolic syndrome was significantly higher among patients with higher AIP. Conclusion. AIP represents a clinically convenient indicator for the detection of T2DM with high risk of complications and associated diseases and thus is a good predictor and indicator for follow-up monitoring in the treatment of patients with high-risk type 2 diabetes.


2020 ◽  
Vol 25 (4) ◽  
pp. 307-315 ◽  
Author(s):  
Xing Wang ◽  
Yan He ◽  
Tao Wang ◽  
Chunming Li ◽  
Zihui Ma ◽  
...  

Purpose: This study aims to analyze the treatment patterns and goal attainment of low-density lipoprotein cholesterol (LDL-C) among patients with atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus (DM) in the real-world setting in Fuzhou, China. Methods: Patients aged ≥20 years with a valid LDL-C measurement (index date) in 2016 were selected from National Healthcare Big Data in Fuzhou, China. Patients were stratified into mutually exclusive cardiovascular risk categories: ASCVD (including recent acute coronary syndrome [ACS], chronic coronary heart disease [CHD], stroke, and peripheral arterial disease [PAD]), and DM alone (without ASCVD). Lipid-modifying medication and LDL-C attainment at the index date were assessed. Results: A total of 21 989 patients met the inclusion criteria, including 17 320 (78.8%) with ASCVD and 4669 (21.2%) with DM alone; 47.7% of patients received current statin therapy in the overall cohort (53.5% in ASCVD, 26.5% for DM); 20.5% ASCVD population achieved LDL-C target with the highest in patients with recent ACS (33.8%), followed by chronic CHD (21.2%), PAD (20.9%), and ischemic stroke (17.3%); 49.0% of patients with DM achieved LDL-C target. Higher LDL-C attainment was observed in high-intensity statin and a combination of statin and nonstatin groups. Atorvastatin was the most commonly used statin with the highest LDL-C attainment, followed by rosuvastatin. Conclusion: Compared with previous studies in China, our study found a relatively low statin use and LDL-C target attainment, but higher than similar studies in Europe. Guidelines should be well complied and more prescription of high-intensity statin or statin and nonstatin combination should be advocated.


2019 ◽  
Vol 26 (9) ◽  
pp. 930-949 ◽  
Author(s):  
C Macchi ◽  
M Banach ◽  
A Corsini ◽  
CR Sirtori ◽  
N Ferri ◽  
...  

Regulation of pro-protein convertase subtilisin/kexin type 9 (PCSK9) by drugs has led to the development of a still small number of agents with powerful activity on low-density lipoprotein cholesterol levels, associated with a significant reduction of cardiovascular events in patients in secondary prevention. The Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) and Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES) studies, with the two available PCSK9 antagonists, i.e. evolocumab and alirocumab, both reported a 15% reduction in major adverse cardiovascular events. Regulation of PCSK9 expression is dependent upon a number of factors, partly genetic and partly associated to a complex transcriptional system, mainly controlled by sterol regulatory element binding proteins. PCSK9 is further regulated by concomitant drug treatments, particularly by statins, enhancing PCSK9 secretion but decreasing its stimulatory phosphorylated form (S688). These complex transcriptional mechanisms lead to variable circulating levels making clinical measurements of plasma PCSK9 for cardiovascular risk assessment a debated matter. Determination of total PCSK9 levels may provide a diagnostic tool for explaining an apparent resistance to PCSK9 inhibitors, thus indicating the need for other approaches. Newer agents targeting PCSK9 are in clinical development with a major interest in those with a longer duration of action, e.g. RNA silencing, allowing optimal patient compliance. Interest has been expanded to areas not only limited to low-density lipoprotein cholesterol reduction but also investigating other non-lipid pathways raising cardiovascular risk, in particular inflammation associated to raised high-sensitivity C-reactive protein levels, not significantly affected by the present PCSK9 antagonists.


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