Use Of Lipid-lowering Drugs Research Articles

Long-term prognostic value of LDL-C, HDL-C, lp(a) and TG levels on cardiovascular disease incidence, by body weight status, dietary habits and lipid-lowering treatment: the ATTICA epidemiological cohort study (2002–2012)

BackgroundThe link between blood lipids and cardiovascular disease (CVD) is complex. Our aim was to assess the differential effect of blood lipids on CVD risk according to age, sex, body weight, diet quality, use of lipid-lowering drugs and presence of hypercholesterolemia.MethodsIn this secondary analysis of the ATTICA prospective cohort study, serum blood lipids, i.e., total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and liproprotein(a) [Lp(a)], and sociodemographic, anthropometric, lifestyle and clinical parameters were evaluated at baseline (2001/2002) in 2020 CVD-free men and women. CVD incidence was recorded at the 10-year follow-up (2011/2012).ResultsAll blood lipids assessed were univariately related to CVD risk; however, associations remained significant only for HDL-C and TG in multivariate models adjusted for age, sex, body mass index, smoking, Mediterranean Diet Score, physical activity, presence of hypercholesterolemia, hypertension and diabetes mellitus, use of lipid-lowering drugs, and family history of CVD [RR per 1 mg/dL (95% CI): 0.983 (0.967, 1.000) and 1.002 (1.001, 1.003), respectively]. In stratified analyses, TC and LDL-C predicted CVD risk in younger subjects, normal-weight subjects, and those not on lipid-lowering drugs, while HDL-C and TG were significant predictors in older subjects, those with low adherence to the Mediterranean diet, and hypercholesterolemic subjects; a significant effect on CVD risk was also observed for TG in males, overweight participants and lipid-lowering medication users and for Lp(a) in older subjects and females (all p ≤ 0.050).ConclusionsThe impact of blood lipids on CVD risk differs according to several biological, lifestyle and clinical parameters.

Serum neurofilament light chain: a novel biomarker for early diabetic sensorimotor polyneuropathy

Aims/hypothesisNo established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.MethodsThis cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.ResultsDSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.Conclusions/interpretationOur findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.Graphical abstract

Systematic review on sex differences for drug use after stroke

Systematic reviews and meta-analyses have synthetized the existing knowledge on sex-differences for the risk of stroke, the most recent ones highlighting an increased risk of stroke for women. However, whether there are sex differences in post stroke treatment in real world setting is not known. We therefore conducted a systematic review on this subject. All observational studies on sex-differences in poststroke drug use published until 20/04/2021 were identified from PubMed and Scopus. Articles were selected and assessed by two independent readers; a third resolved disagreements. Data extraction was performed using a standardized form; articles quality was assessed using the STROBE guidelines. The study is registered on PROSPERO: CRD42021250256. Of the 604 identified articles, 33 were included. Most were published before 2015 and presented methodological limitations. These limitations differentially affected studies with statistically significant and non-significant results, questioning the reliability of conflicting results. The exploration of sex-differences in drug use varied between therapeutic classes (articles focusing on thrombolytics: 25; antithrombotics: 23; on antihypertensive: 13; lipid-lowering drugs: 9). After stroke, women were found less likely to be prescribed antithrombotics in 48% of the articles investigating this class, and lipid-lowering drugs in 56%. Thirty-one percent of the studies concerning antihypertensive drugs reported the opposite. In women, a lack of use of antithrombotics and lipid-lowering drugs after stroke seem to emerge from this review. Conflicting results regarding sex-differences might relate to methodological limitations in studies with no statistical differences, and advocate for the conduct of newer and more comprehensive research.

Time trends of cardiovascular risk management in type 1 diabetes - nationwide analyses of real-life data

BackgroundIndividuals diagnosed with and treated for type 1 diabetes (T1D) have increased risk of micro- and macrovascular disease and excess mortality. Improving cardiovascular (CV) risk factors in individuals with T1D is known to reduce diabetes- related CV complications.AimTo examine time trends in CV risk factor levels and CV-protective treatment patterns. Additionally, examine incidence rates of diabetes-related CV complications in relation to exposure CV-protective treatment.MethodsWe analysed records from 41,630 individuals with T1D, registered anytime between 1996 and 2017 in a nationwide diabetes register. We obtained CV risk factor measurements (2010–2017), CV-protective drug profiles (1996–2017) and CV complication history (1977–2017) from additional nationwide health registers.ResultsFrom 2010 to 2017 there were decreasing levels of HbA1c, LDL-C, and blood pressure. Decreasing proportion of smokers, individuals with glycaemic dysregulation (HbA1c ≥ 58 mmol/mol), dyslipidaemia (LDL-C > 2.6 mmol/l), and hypertension (≥ 140/85 mmHg). Yet, one fifth of the T1D population by January 1st, 2017 was severely dysregulated (HbA1c > 75 mmol/mol). A slight increase in levels of BMI and urinary albumin creatinine ratio and a slight decrease in estimated glomerular filtration rate (eGFR) levels was observed. By January 1st, 2017, one fourth of the T1D population had an eGFR < 60 ml/min/1.73 m2. The proportion of the T1D population redeeming lipid-lowering drugs (LLDs) increased from 5% in 2000 to 30% in 2010 followed by a plateau and then a decline. The proportion of the T1D population redeeming antihypertensive drugs (AHDs) increased from 28% in 1996 to 42% in 2010 followed by a tendency to decline. Use of LLDs was associated with lower incidence of micro- and macrovascular complications, while use of AHDs had higher incidence of CVD and CKD, when compared to non-use and discontinued use, respectively.ConclusionImprovements were seen in CV risk factor control among individuals with T1D in Denmark between 2010 and 2017. However, there is clearly a gap between current clinical guidelines and clinical practice for CV risk management in T1D. Action is needed to push further improvements in CV risk control to reduce CVD and the related excess mortality.

Abstract 9614: Association Between Myocardial Contraction Fraction and Heart Failure Subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Myocardial contraction fraction (MCF) is a non-ejection fraction volumetric measure of myocardial shortening which has been associated with incident heart failure (HF) including in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. However, less is known regarding MCF’s prediction of HF subtypes. Methods: This analysis included men and women aged 45-84 free of clinical cardiovascular disease who underwent cardiac magnetic resonance imaging (cMRI) during the baseline MESA examination and who had data regarding incident adjudicated definite or probable HF events. MCF was calculated using cMRI measurements and defined as the ratio of stroke volume to myocardial volume. HF subtypes were divided into HF with ejection fraction (EF) &lt; 50% (HF EF &lt; 50%, including HF with reduced EF (EF ≤ 40%) and HF with mildly reduced EF (EF 41-49%) and HF with preserved EF (HFpEF, EF ≥ 50%). Cox proportional hazards regression was used to examine the association between MCF and incident HF subtype per decile increase in MCF. Event time was defined as time of first defined HF subtype, and censoring occurred at death or end of follow-up. After an incident HF event, participants were not at risk for another HF subtype. Covariates adjusted for were age, gender, race-ethnicity, education, body-mass index, tobacco and alcohol use, systolic blood pressure (BP), diabetes, physical activity, total cholesterol, and BP and lipid lowering drug use. Results: Among 4,983 participants (mean age 61, 52% female, 61% non-White) over a maximum of 18 years follow-up, there were 275 incident HF events (142 HF EF &lt; 50%, 113 HFpEF, 20 unknown EF). MCF differed across HF status (p&lt;0.001) . Participants without incident HF had a higher mean MCF (0.65) compared to HFpEF (0.62), HF EF &lt; 50% (0.53), and unknown EF (0.52). The adjusted risk of any HF was reduced (HR 0.86, 95% CI 0.82, 0.91) per decile increase of MCF. MCF was strongly associated with incident HF EF &lt; 50% (adjusted HR 0.80, CI 0.74, 0.86) but was not associated with HFpEF (adjusted HR 0.98, CI 0.91, 1.05). Conclusions: In a multi-ethnic cohort, increasing MCF is associated with a decreased risk of incident HF EF&lt;50%. MCF is not significantly associated with incident HFpEF, suggesting different etiologic pathways for these two HF subtypes.

Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans

Background/aimsTo investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population.MethodsWe included 38 694 adults from 14 population-based and hospital-based studies from...

Twenty-first century epidemiology of dyslipidemia in Greece: EMENO national epidemiological study

BackgroundGreece was recently reclassified from low- to medium-risk country in terms of cardiovascular disease, with 27% of cardiovascular deaths attributed to hypercholesterolemia. EMENO nationwide survey (2013-2016) assessed the epidemiology of dyslipidemia in the general population in Greece. MethodsA random sample of adults was drawn by multistage stratified random sampling based on 2011 census. Standardized questionnaires and blood tests for total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and triglycerides were used. Hypercholesterolemia was defined as TC ≥ 240/200 mg/dL and/or the use of lipid-lowering drugs, hyper-LDL-cholesterolemia as LDL-C ≥160/130/100 mg/dL and/or the use of drugs, hypo-HDL-cholesterolemia as HDL-C <40 mg/dL, and hypertriglyceridemia as triglycerides ≥150 mg/dL. Weighted analysis was applied to adjust for study design, age/sex distribution discrepancies between sample and population and nonresponse. ResultsOf 6,006 individuals recruited, 4,298 were analyzed (mean [SD] age 49.2 [18.5] years, men 48.5%, BMI 28.2 [5.7] kg/m2). Mean TC, LDL-C, HDL-C, and TG were 193.9 [44.4], 118.5 [37.6], 49.1 [14.9], and 130.8 [94.4] mg/dL, respectively. The prevalence of hypercholesterolemia was 27.6/52.4% for thresholds ≥240/200 mg/dL, and of hyper-LDL-cholesterolemia was 26.3/46.7/74% for thresholds ≥160/130/100 mg/dL, with no differences between sexes. The prevalence of hypo-HDL-cholesterolemia was 27.5% (men/women 38.1/17.5%, p < 0.001) and of hypertriglyceridemia was 27.8% (men/women 32.6/23.4%, p < 0.001). Lipid-lowering drugs were used by 14.1% of the participants (men/women 12.6/15.6%, p < 0.001). ConclusionsMore than 50% of adults in Greece have some type of dyslipidemia (mainly TC ≥ 200 mg/dL) and 14% are treated. Nationwide programmes are needed to manage dyslipidemia and halt the increasing rate of cardiovascular disease in Greece.

Comparison of severe hypercholesterolemia patients with and without pathogenic variants

Abstract Introduction A pathogenic variant causally related to familial hypercholesterolemia (FH) is found in less than half of adults with severe hypercholesterolemia. The characteristics of adults with severe hypercholesterolemia without pathogenic variant have been poorly described, and it remains unclear whether intensive preventive strategies should be recommended. In this study we compared the characteristics of adults with severe hypercholesterolemia with and without pathogenic variant for FH. Methods Between November 2020 and February 2022, we recruited individuals older than 16 years with a Dutch Lipid Clinic Network (DLCN) score ≥6 and genotyped LDLR, APOB and PCSK9. Participants were part of the multicenter CATCH study, testing the implementation of genetic cascade screening for FH in Switzerland. All genetic analyses were performed in a single central laboratory. Variants classified as likely pathogenic or pathogenic were interpreted as FH-causing. We also assessed socio-economic status, cardiovascular risk factors, lifestyle behavior, and use of lipid-lowering drugs. Results In total, 150 non-related adults with a DLCN score of ≥6 were included, out of whom 62 (41.3%) had genetically confirmed FH. Most variants were found in the LDLR gene (77%). Overall, 70% were using a lipid-lowering drug and 20% were current smokers. Compared to adults with genetically confirmed FH, those without pathogenic variants were older (57.6 vs 50.4 years old), had lower untreated LDL-cholesterol levels (p&amp;lt;0.001), higher triglyceride levels (p=0.032), higher BMI (p=0.014), and had more frequently hypertension (62.5% vs 36.1%). No socio-economic differences were observed. Although adherence to Mediterranean diet was higher among adults without pathogenic variant, they reached less frequently the recommended level of physical activity than adults with genetically confirmed FH (66.2% vs 82.1%). Xanthomas or xanthelasmas, but not corneal arcus, were more frequent among genetically confirmed FH (5.7% vs 20.3%). Conclusions Adults with severe hypercholesterolemia and without a pathogenic FH variant had less optimal control of cardiovascular risk factors than genetically confirmed FH. One fifth were smokers and one third of all patients included in this study were not taking any lipid-lowering drugs, regardless of the presence of a pathogenic variant. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss Heart Foundation

Chinese expert consensus on management of dyslipidemia in the elderly

Dyslipidemia is an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Statins delay the occurrence and development of ASCVD, and reduce the risk of cardiovascular events and death. Due to safety concerns, there exist insufficient use of lipid-lowering agents and a high withdrawal rate of the agents in the elderly. To promote the prevention and treatment of ASCVD, this expert consensus is issued and focuses on the management of dyslipidemia of Chinese elderly basing on the clinical evidence of the use of lipid-lowering drugs by the elderly, and the lipid management guidelines and expert consensus recommendations at home and abroad.

Educational level differences in the primary and secondary prevention of stroke

The aim of this study is to estimate the educational level differences in the primary and secondary prevention of stroke among the Chinese population. Data were obtained from the China Kadoorie Biobank (CKB) survey of 512,891 people aged 30–79 years in 10 geographic regions of China, which was conducted from 2002 to 2008. The Prediction for Atherosclerotic Cardiovascular Disease Risk in China model was used to identify individuals with a high estimated 10-year stroke risk. A total of 8884 participants (1.7%) had established stroke and 218,972 (42.7%) had a high stroke risk. In both primary and secondary prevention, the participants' educational level was positively associated with the control of smoking, blood pressure, consuming a healthy diet, and the use of antiplatelet, BP-lowering medications but negatively associated with higher physical activity levels (all Ptrend < 0.001). In addition, the positive associations were observed with the control of drinking and use of anti-hyperglycaemia medication for primary prevention (all Ptrend < 0.001) and with the use of lipid-lowering medication for secondary prevention (Ptrend = 0.019). The results of the interaction between education level and prevention level showed that, compared with participants in primary prevention, educational level disparities in those with secondary prevention had significantly higher use of antiplatelets and lipid-lowering drugs, achieving the physical activity goal and non-current drinker (all Pfor interaction < 0.05). A higher education level was associated with an increased acceptance of primary and secondary prevention strategies (not smoking or drinking, consuming a healthier diet) except for engaging in a suitable level of physical activity.

COVID-19, dyslipidemia and familial hypercholesterolemia: an up-date

COVID-19 (coronavirus disease 2019) is an infection caused by the SARS-CoV-2 coronavirus, which can evolve into a severe respiratory condition, affecting the world population in a pandemic manner. In this study, we aimed to update the findings of the mechanisms that associate dyslipidemia with COVID-19 infection, the evolution of severe form and the influence of lipid-lowering treatment on outcomes. The search was performed in the PubMed and Embase databases and the selection was based on dyslipidemia and COVID-19 studies, which resulted in 31 articles. In results, the evidence in changes in cholesterol metabolism was found in SARS-CoV-2 virus infection with variations in high-density lipoprotein (HDL) levels. In addition, it provided an increase in triglycerides (TG) and very-low-density lipoprotein cholesterol (VLDLc). Patients with familial hypercholesterolemia (FH) with COVID-19 representing a group of individuals who develop early atherosclerotic disease with a higher risk of cardiovascular event, which should intensify the lipid-lowering treatment due to the potential risk of coronary endothelial dysfunction caused by viral infection. Cholesterol modifying drugs have a potential to change the life cycle of the virus, resulting in a range of pleiotropic effect on infectivity, immunity and inflammation, such as statins, fibrates, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (iPCSK9), omega-3 fatty acids, bile acids sequestrants and nicotinic acid. As dyslipidemia is one of the main risk factors for the severe form of COVID-19, causing endothelial dysfunction previously installed in dyslipidemic patients, the use of lipid-lowering drugs can reduce the risk factors for the unfavorable outcome in these patients.

The general trend of combined use of lipid-lowering drugs

胆固醇升高是动脉粥样硬化性心血管疾病（ASCVD）的核心致病性危险因素。致动脉粥样硬化脂蛋白胆固醇水平受多种载脂蛋白、受体、酶等代谢的调节。目前他汀类药物仍是降低胆固醇防控ASCVD风险的基石，但其单药治疗的血脂达标率远不理想。近些年来不同作用机制的靶向新型降脂药物研发取得突破性进展，以他汀类药物为基础的联合降脂治疗可实现较为理想的胆固醇管理，并带来了ASCVD风险乃至全因死亡风险的显著下降。联合降脂治疗逐渐成为管控ASCVD风险的大趋势。.

Abstract LB158: Total, LDL-, HDL-cholesterol, apolipoproteins, and triglycerides and risk fatal prostate cancer in black and white men in the ARIC study

Abstract Background: Cholesterol reduction is considered a mechanism through which lipid-lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations of total cholesterol with advanced stage and grade in White men based mostly on cholesterol at baseline, whether associations for total cholesterol, low (LDL)- and high (HDL)-density lipoprotein cholesterol, apolipoprotein B (LDL particle component) and A1 (HDL particle component), and triglycerides exist for fatal prostate cancer and in Black men using time-updated biomarkers is unknown. Methods: We conducted a prospective study of 1,553 Black and 5,071 White cancer-free men attending visit 1 (1987-1989) of the Atherosclerosis Risk in Communities Study. Death from prostate cancer was ascertained from the underlying cause on death certificates. Follow-up began at visit 1 and ended at date of death, loss to follow-up, or 12/31/2018, which ever came first. There were 128 deaths from prostate cancer (43 in Black men, 85 in White men) ascertained over 153,184 person years of follow-up (mean 23 years). We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for fatal prostate cancer per 1-standard deviation increment and for tertiles (T1-T3) of time-updated lipid biomarkers adjusting for baseline age, education, race and field center, and updated BMI, waist circumference, smoking status, hyperglycemia and diagnosed diabetes, aspirin use, and lipid-lowering drug use overall, and in Black and White men. Results: Higher total cholesterol concentration was associated with higher fatal prostate cancer risk in White men only (HR per-1 SD=1.25; 95%CI=1.00-1.58), and higher concentration of LDL cholesterol appeared to be associated with fatal prostate cancer in White men only (HR per-1 SD=1.26; 95%CI=0.99-1.60). Apolipoprotein B was non-linearly associated with fatal prostate cancer overall (T2 vs. T1 HR=1.66; 95% CI=1.05-2.64) and in Black men (T2 vs. T1 HR=3.59; 95% CI=1.53-8.40) but not in White men (T2 vs. T1 HR=1.13; 95% CI=0.65-1.97). HRs were &amp;gt;1 overall (T3 vs. T1 HR=1.18) and in Black men (T3 vs. T1 HR=2.11) but were not statistically significant. HDL-cholesterol, Apolipoprotein A1 and triglycerides were not associated with fatal prostate cancer overall and by race. Tests for statistical interaction by race were not statistically significant. Conclusion: Positive associations with fatal prostate cancer were observed with total and LDL-cholesterol in White men, and apolipoprotein B in Black men. These findings may improve the understanding of lipid metabolism in prostate carcinogenesis, and further emphasize the importance of cholesterol control. Support: NHLBI contracts, NCI grants, NPCR Citation Format: Michael T. Marrone, Anna E. Prizment, David Couper, Kenneth R. Butler, Brad C. Astor, Corinne E. Joshu, Elizabeth A. Platz, Alison M. Mondul. Total, LDL-, HDL-cholesterol, apolipoproteins, and triglycerides and risk fatal prostate cancer in black and white men in the ARIC study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB158.

Associations of Socioeconomic Status and Healthy Lifestyle With Incidence of Dyslipidemia: A Prospective Chinese Governmental Employee Cohort Study.

ObjectiveThe purpose of the study was to test whether primary lifestyles mediate associations of SES with incidence of dyslipidemia and to explore interaction relations of lifestyles and SES with incidence of dyslipidemia.MethodsWe included 9,901 individuals at baseline from January 2018 to November 2019, and incidence data were updated to 31 December 2020. Dyslipidemia was defined as total cholesterol (TC) 6.2 mmol/L TC ≥ or triglycerides (TG) ≥2.3 mmol/L or low-density lipoprotein cholesterol (LDL-C) ≥4.1 mmol/L or high-density lipoprotein cholesterol (HDL-C) <1.0 mmol/L; or physician diagnosed dyslipidemia or lipid-lowering drugs use. Lifestyles, socioeconomic factors, and personal characteristics were collected by a questionnaire. A latent class analysis based on education, family income, and occupational position was used to assess the SES. Lifestyle score was calculated using cigarette smoking, alcohol consumption, physical activity, and diet. Cox proportional hazard models and multivariate analyses were used to explore the associations. The mediation effect was evaluated using bootstrap method.ResultsParticipant mean age was 36.5 years (SD = 0.11). The cumulative incidence of dyslipidemia was 11.0% over a mean follow-up of 13.4 months. Compared with participants of high SES, those with low SES had higher risk of incidence of dyslipidemia [hazard ratio 1.32, 95% confidence interval (CI): 1.01–1.73], after adjusting for lifestyle scores and other covariates. The proportion mediated by lifestyles was 5.41% (95%CI: 4.17–7.11). A significant additive interaction was found between lifestyles and SES, whereas association between lifestyle and incidence of dyslipidemia was stronger among those of high SES. Additionally, individuals with low SES and no or one healthy lifestyle behavior had a higher risk of developing dyslipidemia than those with high SES and 3 or 4 healthy lifestyles.ConclusionUnhealthy lifestyles play a small moderating role in socioeconomic inequity in incidence of dyslipidemia among Chinese governmental employees, suggesting that promoting healthy lifestyles alone may not significantly reduce socioeconomic inequalities in health, and measures to address other social determinants of health should also be considered alongside.

81-OR: High Throughput Proteomics Identifies Neurofilament Light Chain (NFL) as a Novel Blood Biomarker for Detection of Diabetic Sensorimotor Polyneuropathy

Background: The neurofilament light chain (NFL) is a polypeptide abundant in neuronal axons, reflecting ongoing neuroaxonal degeneration when detected in the blood. However, no previous study has explored NFL as a potential biomarker for diabetic sensorimotor polyneuropathy (DSPN) , a neurodegenerative disease of the peripheral nervous system commonly found in individuals with diabetes. We hypothesized that higher serum NFL levels are associated with DSPN. Methods: We used data from the German Diabetes Study, a prospective observational study that includes adults with recent-onset diabetes (&amp;lt;1 year) . DSPN was assessed using Toronto consensus criteria. Serum levels of NFL were measured using proximity extension assay, and Poisson regression was used to estimate associations between serum NFL and prevalent DSPN. Results: From a total of 423 participants, 66 (16%) had DSPN. Serum NFL was inversely correlated with age, eGFR and nerve conduction velocities in motor and sensory nerves (all P Spearman &amp;lt;0.0001) . After adjustment for age, sex, waist circumference, height, HbA1c, diabetes duration, diabetes type, cholesterol, eGFR, hypertension, cardiovascular diseases, use of lipid-lowering drugs, and NSAIDs, higher serum levels of NFL were associated with prevalent DSPN (RR (95% CI) 1.92 (1.50, 2.45) (P &amp;lt; 0.0001) . Conclusion: NFL might be useful for detecting DSPN in recent-onset diabetes, but validation in other studies will be required. Considering the absence of FDA-approved biomarkers for DSPN, NFL might be a promising biomarker that could improve the management of DSPN. Disclosure H. Maalmi: None. A. Strom: None. S.M. Hauck: None. G.J. Bönhof: None. W. Rathmann: Consultant; IQVIA Inc. Speaker's Bureau; Boehringer Ingelheim International GmbH, Novo Nordisk. S. Trenkamp: None. V. Burkart: None. J.M. Szendroedi: Consultant; Boehringer Ingelheim International GmbH. D. Ziegler: None. M. Roden: Advisory Panel; Eli Lilly and Company. Research Support; Boehringer Ingelheim International GmbH, Nutricia. Speaker's Bureau; Novo Nordisk. C. Herder: Research Support; Sanofi. Funding DZD (FKZ82DZD02D2G)

PROGNOSTIC CUTOFF OF TRIGLYCERIDES PREDICTING CARDIOVASCULAR OUTCOME IN A LARGE REGIONAL-BASED ITALIAN DATABASE

Objective: Searching for a prognostic cut-off value of triglycerides (TG) in predicting cardiovascular (CV) outcome in a large regional-based Italian database of men and women. Design and method: A nationwide multicentre database collects data on subjects aged 18 to 95 years recruited on a regional community basis from all the territory of Italy with at least 1 measure of TG and a mean follow-up of 110.1 ± 64.3 months. A total of 18,784 subjects were included in the analysis. CV outcome was defined on the basis of ICD10 codes and double-checked with general practitioners and hospital files. Multivariate dichotomic Cox regression models having CV outcome as dependent variable, adjusted for age, sex, serum uric acid, body mass index, total and HDL-cholesterol, arterial hypertension, diabetes, chronic renal disease, smoking habit, use of antihypertensive and lipid lowering drugs were preliminarily used to search for an association between TG log-transformed as a continuous variable and CV event. The conventional cut-off value of TG (150 mg/d) and the prognostic cut-off value of TG identified by means of receiver operating characteristics (ROC) curves, both able to discriminate between subjects developing a CV event, were used as independent predictors in further multivariate Cox models adjusted for the confounders listed above. Results: During 172,329 person-years of follow-up, 1910 participants experienced CV events (11.1 per 1000 age-adjusted person-years). In Cox analysis, TG as a continuous variable was a significant predictor of CV event [odds ratio, OR, 1.189 (1.060–1.334), p = 0.003]. ROC curve showed that &gt; 105 mg/dl (95%CI 75.8–129.3, sensitivity 61.7, specificity 48.8, p &lt; 0.0001) was the prognostic cut-off value for CV event. The conventional cut-off (150 mg/dl) and that identified by ROC curve (105 mg/dl) were both accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.157 (95%CI 1.037–1.290, p = 0.009) and 1.137 (95%CI 1.023–1.263, p = 0.016), respectively. Nevertheless, we observed that cut-offs of TG between 89 and 105 mg/dl, when played in the multivariate Cox analyses, seems to be protective as well. Conclusions: In conclusion, lower than expected prognostic cut-off value of TG for CV event do exist.

Non-alcoholic Fatty Liver Disease Is Associated With Aortic Calcification: A Cohort Study With Propensity Score Matching.

ObjectivesNon-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis.MethodsThis prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort.ResultsOf the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0–55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02–1.38) and 1.18 (1.01–1.38), respectively (both p < 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes.ConclusionsNAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.

Abstract EP35: Longitudinal Lipidomic Profiling Of Left Ventricular Mass In American Indians: The Strong Heart Study

Background: Dyslipidemia is a major risk factor for CVD. Left ventricular mass (LVM) is an independent predictor of heart failure and other cardiovascular events. It is unclear whether and how altered plasma lipidome (all lipids in a plasma sample) affects LVM. The relationship between longitudinal change in plasma lipidome and change in LVM is also unstudied in any racial/ethnic group. Objective: To identify molecular lipid species associated with LVM, independent of traditional risk factors. Methods: Using an untargeted LC-MS, we repeatedly measured 1,542 lipids in 3,162 fasting plasma samples collected at two time points (2001-2003, 2006-2009, mean 5.5 years apart) from 1,581 American Indians in the Strong Heart Family Study. All participants were free of overt CVD at both time points. LVM was measured by M-mode echocardiography and LVM index (LVMI) was calculated as LVM/height 2.7 . Lipids associated with LVMI were identified by generalized estimating equation (GEE) models, adjusting for age, sex, center, BMI, smoking, blood pressure, renal function, LDL-c, and diabetes. We first conducted the analysis at each time point, separately, and then combined the results by meta-analysis. The longitudinal association between change in lipids and change in LVMI was examined by GEE, adjusting for the same covariates plus baseline lipids and LVMI. Multiple testing was controlled by false discovery rate at 0.05. Results: The mean age of participants was 39.8 years (62.5% women) at baseline and 45.1 years at follow-up. We identified 325 lipids (125 known), largely fatty acyls, sterol lipids, sphingolipids, glycerolipids, and glycerophospholipids, significantly associated with LVMI at both time points. Longitudinal changes in 17 lipids, including glycerolipids, glycerophospholipids, and sphingolipids, were either positively (ORs: 1.09 -1.95) or negatively (ORs: 0.50 - 0.69) associated with change in LVMI over 5 years of follow-up. Changes in lipids explain up to 1.58% of the variability in the change of LVMI during follow-up. Additional adjustments for use of anti-hypertensive and lipid-lowering drugs did not change the results. Conclusion: Altered fasting plasma lipidome and its longitudinal change over time were significantly associated with LVMI beyond clinical factors and baseline lipids. Our results shed light on the mechanisms through which dyslipidemia may affect LV remodeling, thereby contributing to heart failure or other cardiovascular events.

Prevalence of lipid-lowering drug use

Prevalence of lipid-lowering drug use

Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes

Background and aimBased on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM). Methods and resultWe measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system.Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype. ConclusionsThe C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.