scholarly journals Elevated Triglycerides (≥150 mg/dL) and High Triglycerides (200–499 mg/dL) Are Significant Predictors of Hospitalization for New-Onset Kidney Disease: A Real-World Analysis of High-Risk Statin-Treated Patients

2019 ◽  
Vol 9 (6) ◽  
pp. 400-407 ◽  
Author(s):  
Peter P. Toth ◽  
Sephy Philip ◽  
Michael Hull ◽  
Craig Granowitz
Keyword(s):  
High Risk ◽  
Kidney Disease ◽  
Real World ◽  
Density Lipoprotein ◽  
Cox Proportional Hazards Model ◽  
Lipoprotein Cholesterol ◽  
Administrative Claims ◽  
Atherosclerotic Cardiovascular Disease ◽  
Research Database ◽  
New Onset

Background: Dyslipidemia in kidney disease (KD) involves increased levels of triglycerides (TG) and TG-rich lipoproteins, with only minor changes in low-density lipoprotein cholesterol. The increasing prevalence of diabetic KD and the shared atherogenic lipid profile between KD and diabetes underscore the importance of understanding dyslipidemia in these patients. Previous studies suggest an association between elevated TG and new-onset KD. Additional data are needed to better define the relationship between hypertriglyceridemia and new-onset KD. Objective: To evaluate the real-world impact of elevated and high TG on risk of KD in high-risk statin-treated patients. Methods: This retrospective administrative claims analysis of the Optum Research Database included statin-treated patients (age ≥45 years) with diabetes and/or atherosclerotic cardiovascular disease who were followed for ≥6 months. Cohorts included patients with elevated TG (≥150 mg/dL; n = 27,471) or high TG (200–499 mg/dL; subgroup of elevated TG cohort; n = 13,411), and a comparator cohort (TG <150 mg/dL and high-density lipoprotein cholesterol >40 mg/dL; n = 32,506). The probability of hospitalization for new-onset KD was calculated post hoc from multivariate analyses controlled for patient characteristics and comorbidities using a Cox proportional hazards model. Results: The rate of hospitalization for new-onset KD was 31% higher in the elevated-TG cohort (hazard ratio [HR], 1.311; 95% confidence interval [CI], 1.228–1.401; p < 0.001) and 45% higher in the high-TG cohort (HR, 1.451; 95% CI, 1.339–1.572; p < 0.001) compared with the respective comparator cohorts. Conclusions: In a real-world analysis of statin-treated patients with high cardiovascular risk, both elevated TG (≥150 mg/dL) and high TG (200–499 mg/dL) were significant predictors of hospitalization for new-onset KD, identifying hypertriglyceridemia as a potential KD risk factor.

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines

2020 ◽  
pp. 204748732094010
Author(s):  
Konstantinos C Koskinas ◽  
Baris Gencer ◽  
David Nanchen ◽  
Mattia Branca ◽  
David Carballo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Coronary Syndromes

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

scholarly journals Real-world use of PCSK9 inhibitors: A single-center experience

2018 ◽  
Vol 47 (1) ◽  
pp. 265-270 ◽  
Author(s):  
Sinan Sarsam ◽  
Abeer Berry ◽  
George Degheim ◽  
Robby Singh ◽  
Marcel Zughaib
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Profile ◽  
Real World ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
The Impact

Objective Hyperlipidemia is an important risk factor for atherosclerotic cardiovascular disease. Many patients are intolerant to or have limited benefit from statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved for treating hyperlipidemia in these patients. We sought to investigate the impact of these medications in a real-world cardiology practice. Methods This was a retrospective study of 17 patients with either heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) levels above the treatment target despite maximally tolerated statins. Baseline lipid profile was compared with a repeat lipid profile obtained 4 to 6 weeks after initiating treatment with a PCSK9 inhibitor. Results The average duration of PCSK9 inhibitor treatment was 10.7 months. Lipid profile comparison showed that total cholesterol decreased from 243 ± 72 to 148 ± 39 (mg/dL) (39% reduction), triglycerides decreased from 185 ± 86 to 149 ± 62 (mg/dL) (19.5% reduction), high-density lipoprotein cholesterol increased from 56 ± 20 to 62 ± 26 (mg/dL) (10.7% increase), and LDL-C decreased from 154 ± 30 to 57 ± 32 (mg/dL) (63% reduction) from baseline. Conclusions PCSK9 inhibitors as add-on therapy to maximally tolerated statins resulted in an approximately 63% reduction in LDL-C.

Abstract 19949: Attainment of Lipid Levels in Patients at High Cardiovascular Risk: Results from a U.S. Managed Care Population Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Dylan Steen ◽  
Irfan Khan ◽  
Laura K Becker ◽  
Katherine M Gorcyca ◽  
JoAnne Foody
Keyword(s):  
High Risk ◽  
Managed Care ◽  
Index Date ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
High Risk Population ◽  
Profile Measurement ◽  
Research Database ◽  
Coronary Syndrome ◽  
Stable Coronary Heart Disease

Background: Current, generalizable data on low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) as well as triglyceride (TG) levels are necessary to guide health policy decisions, guideline recommendations and treatment innovation. While LDL-C and non-HDL-C are established targets, TG elevations of 150-500 mg/dL and >500 mg/dL can contribute to CV disease and pancreatitis risk, respectively. We evaluated attainment of these lipid measures in a large, managed care population in the US. Methods: The analysis included patients from the Optum Research Database meeting the following criteria: a valid lipid profile measurement in 2012 (i.e. “index date”); ≥20 years of age; continuous enrollment for≥ 2 years; and ≥1 high risk CV condition. Each patient was categorized into a mutually-exclusive category in the following hierarchy: acute coronary syndrome (ACS) within 12 months; stable coronary heart disease (CHD); ischemic stroke; peripheral arterial disease (PAD); and diabetes mellitus. Patients covered by a prescription on the index date or within 30 days were considered to be on treatment. Results: In total, 217,516 patients met the inclusion criteria. Median (Q1 to Q3) age was 61 (53 to 70) years, 51.6% were male, 10.7% were treated with intensive statins, 34.8% with less-intensive statins and 5.8% with nonstatin lipid-modifying therapy. Median LDL-C was 92 (72 to 116) mg/dL, non-HDL-C was 118 (96 to 145) mg/dL and TG was 120 (85 to 169) mg/dL in the overall cohort. The frequency of lipid level achievement is displayed by hierarchical disease state (TABLE). Conclusions: This study is the largest analysis of LDL-C, non-HDL-C and TG levels in a contemporary US managed care high risk population. Statins were underutilized, reflected by inadequate achievement of optimal LDL-C and non-HDL-C levels. While very high TG levels were infrequent, more optimal TG level were only achieved in about two-thirds of the population.

Abstract 13214: Underuse of Combination Pharmacotherapy for Management of Dyslipidemia versus Diabetes and Hypertension Among Patients With Atherosclerotic Cardiovascular Disease (ascvd): Insights From the Getting to an Improved Understanding of Low-density Lipoprotein-cholesterol and Dyslipidemia Management (gould) Registry

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali M Agha ◽  
Mikhail N Kosiborod ◽  
James A De Lemos ◽  
Robert S Rosenson ◽  
Qi Gao ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Combination Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Combination Pharmacotherapy

Introduction: Cardiovascular disease prevention entails treatment of multiple risk factors, including diabetes (DM), hypertension (HTN), and hyperlipidemia (HLD), based on guidelines that promote the use of combination therapy when monotherapy does not achieve treatment goals. The purpose of this study is to determine how frequently combination pharmacotherapy is employed to manage these disorders among patients with atherosclerotic cardiovascular disease (ASCVD), based on the GOULD registry. Methods: The multicenter, observational GOULD registry describes low-density lipoprotein cholesterol (LDL-C) treatment patterns over time in adults with clinical ASCVD in the United States. Patients were enrolled into 3 cohorts: 1) Currently on PCSK9 inhibitor (PCSK9i), or not on PCSK9i with 2) LDL-C 70-99 mg/dL, or 3) LDL-C ≥100 mg/dL. We determined the prevalence of DM and HTN within this registry, the classes of medications used to treat these disorders, and how frequently patients were on two or more medications to treat these disorders at baseline, 6, 12, 18, and 24 months, respectively. Results: Among 5,006 patients in this cohort on lipid-lowering therapy (LLT), 35.2% had DM and 86.0% had HTN at baseline. Of those receiving treatment, 47.6% and 71% were receiving two or more medications for management of DM and HTN, respectively. In contrast, only 19.5% of patients were receiving two or more LLT medications (51.9% among PCSK9i subjects, 15.4% among LDL-C subjects) (Figure). There was a modest increase in combination lipid therapy from 19.5% at baseline to 25.6% at 24 months. Conclusions: Despite recent guidelines supporting the use of combination therapy in patients with high risk ASCVD with an LDL-C above threshold after statin therapy, this high-risk group continues to be managed mostly with statin monotherapy in contrast to the widespread use of combination therapy for the treatment of DM and HTN.

Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?

2021 ◽  
pp. 107424842110236
Author(s):  
Ruihai Zhou ◽  
George A. Stouffer ◽  
Sidney C. Smith
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Outcomes ◽  
Mechanism Of Action ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Lowering ◽  
Cholesterol Levels

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.

scholarly journals Impact of Adoption of Directly Measured Low-Density Lipoprotein-Cholesterol (LDL-C) on Targets of Lipid Control and Its Comparison With Friedewald Formula-Calculated LDL Cholesterol in People With Type-2 Diabetes Mellitus

2020 ◽  
pp. 263246362097804
Author(s):  
Rejitha Jagesh ◽  
Mathew John ◽  
Manju Manoharan Nair Jalaja ◽  
Tittu Oommen ◽  
Deepa Gopinath
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Friedewald Formula

Objectives: The accurate and precise measurement of low-density lipoprotein-cholesterol (LDL-C) is important in the assessment of atherosclerotic cardiovascular disease risk (ASCVD) in people with diabetes mellitus. This study aimed at comparing directly measured LDL-C with Friedewald formula (FF)-calculated LDL-C (c-LDL-C) in people with type-2 diabetes. Methods: Fasting lipid profiles of 1905 people with type-2 diabetes, whose LDL-C was estimated by direct LDL assay, were chosen for the study. In the same group, LDL-C was calculated with FF. Correlation and agreement between these methods were analyzed at various strata of triglycerides (TGs). The possibility of misclassifying people at various levels of LDL-C targets proposed in literature was calculated. Results: The mean LDL-C levels were lower in the c-LDL-C group across various TG strata. A significant correlation was found between c-LDL-C and direct LDL-C for all the study samples ( r = 0.948, P < .001) and across all TG strata. Analysis of agreement showed a positive bias for direct LDL-C which increased at higher strata of TGs. c-LDL-C underestimated ASCVD by misclassifying people at various LDL-C target levels. Conclusion: There is a difference between direct LDL-C and c-LDL-C values in people with diabetes and this may result in misclassifying ASCVD especially at lower levels of LDL-C and higher levels of TGs.

scholarly journals Cigarette smoke inhalation aggravates diabetic kidney injury in rats

2019 ◽  
Vol 8 (6) ◽  
pp. 964-971 ◽  
Author(s):  
Songling Jiang ◽  
Do Van Quan ◽  
Jae Hyuck Sung ◽  
Moo-Yeol Lee ◽  
Hunjoo Ha
Keyword(s):  
Kidney Disease ◽  
Cigarette Smoke ◽  
Density Lipoprotein ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Smoke Inhalation ◽  
Lipoprotein Cholesterol ◽  
Sprague Dawley ◽  
Experimental Conditions ◽  
Diabetic Kidney

Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Epidemiological studies have demonstrated that cigarette smoke or nicotine is a risk factor for the progression of chronic kidney injury. The present study analyzed the kidney toxicity of cigarette smoke in experimental rats with DKD. Experimental diabetes was induced in 7-week-old Sprague-Dawley rats by a single intraperitoneal injection of streptozotocin (60 mg kg−1). Four weeks after the induction of diabetes, rats were exposed to cigarette smoke (200 μg L−1), 4 h daily, and 5 days per week for 4 weeks. Cigarette smoke did not affect the levels of plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol or non-esterified fatty acids in both control and diabetic rats under the experimental conditions. Cigarette smoke, however, significantly increased diabetes-induced glomerular hypertrophy and urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) excretion, suggesting exacerbation of diabetic kidney injury. Cigarette smoke promoted macrophage infiltration and fibrosis in the diabetic kidney. As expected, cigarette smoke increased oxidative stress in both control and diabetic rats. These data demonstrated that four weeks of exposure to cigarette smoke aggravated the progression of DKD in rats.

Sign in / Sign up

Export Citation Format

Share Document