Statin-treated Patients Research Articles

Impact of statin treatment on cardiovascular events in patients with retinal vein occlusion: a nested case-control study in Korea.

Retinal vein occlusion (RVO) is associated with an increased risk of future cardiovascular events. Statin therapy is a key cornerstone in prevention for patients at high cardiovascular risk. However, little is known about the role of statin therapy for patients with RVO. This study evaluated whether statin treatment in patients with RVO was associated with a lower risk of cardiovascular events. A population-based, nested case-control study was conducted with a cohort of newly diagnosed RVO patients without prior cardiovascular disease between 2008 and 2020 using a nationwide health claims database in Korea. From this cohort of RVO patients, we identified cases of cardiovascular events (stroke or myocardial infarction) after RVO and matched controls based on sex, age, insurance type, antiplatelet use, and underlying comorbidities using 1:2 incidence density sampling. Using a cohort of 142,759 patients with newly diagnosed RVO, we selected 6,810 cases and 13,620 matched controls. A significantly lower risk of cardiovascular events (adjusted odds ratio, 0.604; 95% confidence interval, 0.557 to 0.655) was observed in RVO patients with statin treatment than in those without statin treatment. Statin treatment was associated with a reduced risk for both stroke and myocardial infarction after RVO. Longer statin treatment after RVO was associated with a lower risk for cardiovascular events. Statin treatment was associated with a lower risk for future cardiovascular events in patients with newly diagnosed RVO. Further studies are warranted to clarify the potential cardiovascular preventive role of statins in patients with RVO.

Statin Treatment Is Associated with Alterations in the Platelet Lipidome.

Platelets are key players in the pathophysiology of coronary artery disease (CAD) and platelet hyperreactivity leads to increased risk of developing adverse cardiovascular events. Further, significant changes in the platelet lipidome occur in patients with acute coronary syndrome (ACS) and critically regulated lipids lead to platelet hyperresponsiveness. Statin treatment is crucial in the treatment and prevention of patients with CAD by remodeling lipid metabolism. In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics, highlighting significant changes between statin-treated and naïve patients. We characterized the platelet lipidome in a CAD cohort (n = 105) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. Among the annotated lipids, 41 lipids were significantly upregulated in statin-treated patients, whereas 6 lipids were downregulated compared to naïve patients. The most prominent upregulated lipids in statin-treated patients belong to the class of triglycerides, cholesteryl esters, palmitic acid, and oxidized phospholipids, whereas mainly glycerophospholipids were downregulated compared to untreated patients. A more pronounced effect of statin treatment on the platelet lipidome was observed in ACS patients. We further highlight a dose-dependent influence on the platelet lipidome. Our results reveal that the platelet lipidome is altered in CAD patients with statin treatment and upregulated lipids embody mainly characteristic triglycerides, whereas downregulated lipids mostly compromise glycerophospholipids, which may play a role in the pathophysiology of CAD. Results of this study may contribute to the understanding of statin treatment softening the lipid phenotype.

An Android App “Apolipoprotein B Calculator” Calculates Apolipoprotein B Using Regression Analysis and Neural Network – Using the Friedewald Equation is the Same as Directly Measured Low-density Lipoprotein Cholesterol and Better at Low-density Lipoprotein Levels

Background: Apolipoprotein B (Apo B) is an important predictor of the risk of atherosclerotic cardiovascular disease over and above low-density lipoprotein cholesterol (LDL-C), especially in statin-treated patients. Assays of Apo B are not available widely. Objectives: The objective of this study is to derive the Apo B from a lipid profile, using a regression equation and a neural network and compare the results, to compare LDL-C measured by direct assay and a Friedewald equation derived LDL-C in their efficacy to predict Apo B, to determine the effect of lower levels of LDL-C on the prediction models, and to develop an android app “Apo B Calculator” which will calculate the Apo B and also give the predictive accuracy of the result. Methodology: Eight hundred and eighty-five persons were split into a training set and a validation set. Both the regression equation and neural network methods were applied on the training set of 442 patients and the best regression equation and neural network predictive model for Apo B were derived. This was then applied on the validation set of 443 patients to test the R2 of the models. Results: The regression equation Apo B = 25.199 + 0.266 (LDL) + 0.062 (triglycerides level [TGL]) + 0.248 (non-high-density lipoprotein cholesterol) was the best predictor of Apo B when directly measured LDL-C was used. The predictive accuracy of the neural network was lesser than the regression equation (75% vs. 87.4% at 95% confidence interval [CI]). The regression equation for the Friedewald equation derived LDL-C was Apo B = 25.077 + 0.528 friedewald equation (F. LDL) +0.138 (TGL) and was comparable with the neural network (86.4% vs. 85% at 95% CI). The overall efficacy of both the direct assay and Friedewald equation-derived LDL-C were nearly the same (87.4% vs. 86.4% at 95% CI). There was a linear decline in the predictive accuracy of both methods at diminishing LDL-C levels. At lower levels of LDL-C (<70 mg/dl), the accuracy of the Friedewald equation derived LDL-C was a better predictor of Apo B (70% vs. 59.8%). With this data, we developed an android app “Apo B Calculator” which will calculate the Apo B from a directly measured or Friedewald equation derived LDL-C. The app will also mention the predictive accuracy of the results. Conclusions: The regression equation derived from directly measured LDL-C and Friedewald equation derived LDL-C, and the neural network using the Friedewald equation showed near similar efficacy in predicting the Apo B value (87.4%, 86.4%, and 85%). A regression equation using a Friedewald formula is a better predictor of Apo B at LDL-C levels <70 mg/dl. The app “Apo B Calculator” can predict the Apo B from both directly measured and Friedewald equation derived LDL-C and give the predictive accuracy for the method – This will help the clinician to know the Apo B and also the predictive accuracy of such calculated value.

Adherence to statin treatment in patients with familial hypercholesterolemia: A dynamic prediction model

BackgroundStatins are the primary therapy in patient with heterozygous familial hypercholesterolemia (HeFH). Non-adherence to statin therapy is associated with increased cardiovascular risk. ObjectiveWe constructed a dynamic prediction model to predict statin adherence for an individual HeFH patient for each upcoming statin prescription. MethodsAll patients with HeFH, identified by the Dutch Familial Hypercholesterolemia screening program between 1994 and 2014, were eligible. National pharmacy records dated between 1995 and 2015 were linked. We developed a dynamic prediction model that estimates the probability of statin adherence (defined as proportion of days covered >80%) for an upcoming prescription using a mixed effect logistic regression model. Static and dynamic patient-specific predictors, as well as data on a patient's adherence to past prescriptions were included. The model with the lowest AIC (Akaike Information Criterion) value was selected. ResultsWe included 1094 patients for whom 21,171 times a statin was prescribed. Based on the model with the lowest AIC, age at HeFH diagnosis, history of cardiovascular event, time since HeFH diagnosis and duration of the next statin prescription contributed to an increased adherence, while adherence decreased with higher untreated LDL-C levels and higher intensity of statin therapy. The dynamic prediction model showed an area under the curve of 0.63 at HeFH diagnosis, which increased to 0.85 after six years of treatment. ConclusionThis dynamic prediction model enables clinicians to identify HeFH patients at risk for non-adherence during statin treatment. These patients can be offered timely interventions to improve adherence and further reduce cardiovascular risk.

Impact of the eicosapentaenoic acid to arachidonic acid ratio on plaque characteristics in statin-treated patients with coronary artery disease

BackgroundA low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD). ObjectiveTo clarify the impact of the EPA/AA ratio on the characteristics of non-culprit coronary plaques in statin-treated patients with CAD. MethodsA total of 370 consecutive stable coronary disease patients treated with statins, who underwent percutaneous coronary intervention for the culprit lesion and optical coherence tomography (OCT) imaging of the non-culprit plaque in a culprit vessel were included. The characteristics of non-culprit plaques assessed using OCT were compared between the lower EPA/AA group (EPA/AA <0.4, n = 255) and the higher EPA/AA group (EPA/AA ≥0.4, n = 115). ResultsThe prevalence of lipid-rich plaque (58.8 vs. 41.7%, p = 0.003) and plaque with macrophages (56.5 vs. 31.3%, p <0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA group. This association was observed even if the LDL-C level was <100 mg/dL. The prevalence of thin-cap fibroatheroma was significantly higher in patients with lower EPA/AA and higher LDL-C (≥100 mg/dL) than in those with higher EPA/AA and lower LDL-C (<100 mg/dL) (odds ratio: 2.750, 95% confidence interval: 1.182-6.988, p = 0.024). An EPA/AA <0.4 was independently associated with a higher prevalence of lipid-rich plaque, plaque with macrophages, and cholesterol crystals. ConclusionLower EPA/AA ratio was associated with higher prevalence of vulnerable characteristics in non-culprit plaques. The present results suggest the importance of EPA/AA ratio on the secondary prevention of CAD.

Lost Therapeutic Benefit of Delayed Low-Density Lipoprotein Cholesterol Control in Statin-Treated Patients and Cost-Effectiveness Analysis of Lipid-Lowering Intensification

ObjectivesAttainment of low-density lipoprotein cholesterol (LDL-C) therapeutic goals in statin-treated patients remains suboptimal. We quantified the health economic impact of delayed lipid-lowering intensification from an Australian healthcare and societal perspective. MethodsA lifetime Markov cohort model (n = 1000) estimating the impact on coronary heart disease (CHD) of intensifying lipid-lowering treatment in statin-treated patients with uncontrolled LDL-C, at moderate to high risk of CHD with no delay or after a 5-year delay, compared with standard of care (no intensification), starting at age 40 years. Intensification was tested with high-intensity statins or statins + ezetimibe. LDL-C levels were extracted from a primary care cohort. CHD risk was estimated using the pooled cohort equation. The effect of cumulative exposure to LDL-C on CHD risk was derived from Mendelian randomization data. Outcomes included CHD events, quality-adjusted life-years (QALYs), healthcare and productivity costs, and incremental cost-effectiveness ratios (ICERs). All outcomes were discounted annually by 5%. ResultsOver the lifetime horizon, compared with standard of care, achieving LDL-C control with no delay with high-intensity statins prevented 29 CHD events and yielded 30 extra QALYs (ICERs AU$13 205/QALY) versus 22 CHD events and 16 QALYs (ICER AU$20 270/QALY) with a 5-year delay. For statins + ezetimibe, no delay prevented 53 CHD events and gave 45 extra QALYs (ICER AU$37 271/QALY) versus 40 CHD events and 29 QALYs (ICER of AU$44 218/QALY) after a 5-year delay. ConclusionsDelaying attainment of LDL-C goals translates into lost therapeutic benefit and a waste of resources. Urgent policies are needed to improve LDL-C goal attainment in statin-treated patients.

Limited benefit of triglyceride lowering with fibrates in statin-treated patients.

Limited benefit of triglyceride lowering with fibrates in statin-treated patients.

Lipoprotein(a) and residual vascular risk in statin-treated patients with first acute ischemic stroke: A prospective cohort study.

Statins either barely affect or increase lipoprotein(a) [Lp(a)] levels. This study aimed to explore the factors correlated to the change of Lp(a) levels as well as the relationship between Lp(a) and the recurrent vascular events in statin-treated patients with first acute ischemic stroke (AIS). Patients who were admitted to the hospital with first AIS from October 2018 to September 2020 were eligible for inclusion. Correlation between the change of Lp(a) levels and potential influencing factors was assessed by linear regression analysis. Cox proportional regression models were used to estimate the association between Lp(a) and recurrent vascular events including AIS, transient ischemic attack, myocardial infarction and coronary revascularization. In total, 303 patients, 69.6% males with mean age 64.26 ± 11.38 years, completed the follow-up. During the follow-up period, Lp(a) levels increased in 50.5% of statin-treated patients and the mean percent change of Lp(a) levels were 14.48% (95% CI 6.35-22.61%). Creatinine (β = 0.152, 95% CI 0.125-0.791, P = 0.007) and aspartate aminotransferase (AST) (β = 0.160, 95% CI 0.175-0.949, P = 0.005) were positively associated with the percent change of Lp(a) levels. During a median follow-up of 26 months, 66 (21.8%) patients had a recurrent vascular event. The median time period between AIS onset and vascular events recurrence was 9.5 months (IQR 2.0-16.3 months). The on-statin Lp(a) level ≥70 mg/dL (HR 2.539, 95% CI 1.076-5.990, P = 0.033) and the change of Lp(a) levels (HR 1.003, 95% CI 1.000-1.005, P = 0.033) were associated with the recurrent vascular events in statin-treated patients with first AIS. Furthermore, the on-statin Lp(a) levels ≥70 mg/dL (HR 3.612, 95% CI 1.018-12.815, P = 0.047) increased the risk of recurrent vascular events in patients with low-density lipoprotein cholesterol (LDL-C) levels < 1.8 mmol/L. Lp(a) levels increased in half of statin-treated patients with first AIS. Creatinine and AST were positively associated with the percent change of Lp(a) levels. Lp(a) is a determinant of residual vascular risk and the change of Lp(a) is positively associated with the risk of recurrent vascular events in these patients.

Study protocol of the PROUD48 study comparing the effects of pemafibrate and omega-3 fatty acid ethyl esters on ApoB-48 in statin-treated patients with dyslipidaemia: a prospective, multicentre, open-label, randomised, parallel group trial in Japan

IntroductionThis study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual...

Icosapent Ethyl diminishes CVD risk in smokers: REDUCE-IT smoking

Abstract Background/Introduction Cigarette smoking is associated with increased risk of cardiovascular (CV) events with effective treatment currently limited to smoking cessation. REDUCE-IT, a multinational, double-blind trial, randomised 8179 statin-treated patients with controlled low density lipoprotein cholesterol, elevated triglycerides, and CV risk, to icosapent ethyl (IPE) 4 grams/day or placebo, with a median of 4.9 years of follow-up. IPE reduced the primary composite (CV death, nonfatal myocardial infarction [MI], nonfatal stroke, coronary revascularisation, or hospitalisation for unstable angina) and key secondary composite (CV death, nonfatal MI, or nonfatal stroke) endpoints 25% and 26%, respectively (each P&amp;lt;0.0001), and individual components including stroke (28%), MI (31%), cardiac arrest (48%), and sudden cardiac death (31%) (all P≤0.01). Purpose To evaluate the effects of IPE on the risk of CV events and safety measures in patients by history of smoking. Methods The effect of IPE on first and total primary and key secondary endpoints was evaluated in the REDUCE-IT study using post hoc analyses based upon smoking history. Groups were classified as never smokers (n=3264), former smokers (n=3672), and current smokers (n=1241). Results Compared with placebo, IPE use in combined current and former smokers (n=4913) was associated with significant reductions in time to the primary composite endpoint (hazard ratio, 0.77 [95% CI, 0.68–0.87]; P&amp;lt;0.0001) and in total events (rate ratio, 0.71 [95% CI, 0.61–0.82]; P&amp;lt;0.0001) (Figure 1). These benefits remained significant when subdivided into current and former smokers and were associated with reductions in the key secondary composite endpoint (P=0.04, P=0.005), and the individual components of CV death or nonfatal MI (P=0.04, P=0.01) and fatal or nonfatal MI (P=0.009, P=0.01, respectively). Never smokers also had a significant benefit from IPE for both the primary and key secondary endpoints. Overall, there were similar estimated rates of first occurrences of CV death, MI, stroke, coronary revascularisation, or hospitalisation for unstable angina in current smokers (23.8%) and former smokers (23.0%) assigned to IPE compared with never smokers on placebo (25.7%) (Figure 2). Conclusions In the REDUCE-IT study, IPE treatment significantly reduced the risk of CV events in current and former smokers to levels observed in never smokers. While smoking cessation should always be recommended, these data raise the possibility that IPE treatment may markedly attenuate the CV hazards attributable to smoking. Funding Acknowledgement Type of funding sources: None.

HIGH-INTENSITY STATINS COMBINED WITH EICOSAPENTAENOIC ACID (EPA) IMPROVES ENDOTHELIAL FUNCTION DURING EXPOSURE TO OXIDIZED LDL

BackgroundDuring atherosclerosis, endothelial cell (EC) dysfunction results in reduced nitric oxide (NO) bioavailability and increased cytotoxic peroxynitrite (ONOO−). This loss of NO bioavailability results in abnormal vasodilation and inflammatory changes. Eicosapentaenoic acid (EPA) administered as icosapent ethyl (IPE) reduced cardiovascular (CV) events in high-risk patients treated with statins (REDUCE-IT). We tested the effects of high-intensity statins and EPA in ECs exposed to oxidized LDL (oxLDL).Methods and ResultsHuman umbilical vein ECs (HUVECs) were pretreated with 20 mg/dL oxLDL for 20 min, then treated with atorvastatin (active metabolite, ATM) and rosuvastatin (rosuva) at 1.0 μM ± EPA (10μM) for 1 hr. Cells were stimulated with calcium and assayed for the NO/ONOO− release ratio using nanosensors. ECs exposed to oxLDL showed a 60% reduction in NO release compared with vehicle (386±29 to 156±18 nM, p< 0.001) concomitant with a pronounced increase in ONOO− release (205±31 to 283±16 nM, p< 0.001), resulting in a >70% decrease in the NO/ONOO− release ratio (p < 0.001). ECs treated with ATM had an improved NO/ONOO− release ratio (53%) that increased in combination with EPA by 216% (p < 0.01). Similar results were observed for EPA in combination with rosuvastatin. When either statin was combined with EPA, there was also decreased ONOO− release compared to statin alone (p < 0.01).ConclusionIn combination with high intensity statins, EPA enhanced NO bioavailability in dysfunctional human ECs. The ability of EPA to reverse vascular EC dysfunction may lead to reduced ischemic events in statin-treated patients, as evidenced in outcome trials. BackgroundDuring atherosclerosis, endothelial cell (EC) dysfunction results in reduced nitric oxide (NO) bioavailability and increased cytotoxic peroxynitrite (ONOO−). This loss of NO bioavailability results in abnormal vasodilation and inflammatory changes. Eicosapentaenoic acid (EPA) administered as icosapent ethyl (IPE) reduced cardiovascular (CV) events in high-risk patients treated with statins (REDUCE-IT). We tested the effects of high-intensity statins and EPA in ECs exposed to oxidized LDL (oxLDL). During atherosclerosis, endothelial cell (EC) dysfunction results in reduced nitric oxide (NO) bioavailability and increased cytotoxic peroxynitrite (ONOO−). This loss of NO bioavailability results in abnormal vasodilation and inflammatory changes. Eicosapentaenoic acid (EPA) administered as icosapent ethyl (IPE) reduced cardiovascular (CV) events in high-risk patients treated with statins (REDUCE-IT). We tested the effects of high-intensity statins and EPA in ECs exposed to oxidized LDL (oxLDL). Methods and ResultsHuman umbilical vein ECs (HUVECs) were pretreated with 20 mg/dL oxLDL for 20 min, then treated with atorvastatin (active metabolite, ATM) and rosuvastatin (rosuva) at 1.0 μM ± EPA (10μM) for 1 hr. Cells were stimulated with calcium and assayed for the NO/ONOO− release ratio using nanosensors. ECs exposed to oxLDL showed a 60% reduction in NO release compared with vehicle (386±29 to 156±18 nM, p< 0.001) concomitant with a pronounced increase in ONOO− release (205±31 to 283±16 nM, p< 0.001), resulting in a >70% decrease in the NO/ONOO− release ratio (p < 0.001). ECs treated with ATM had an improved NO/ONOO− release ratio (53%) that increased in combination with EPA by 216% (p < 0.01). Similar results were observed for EPA in combination with rosuvastatin. When either statin was combined with EPA, there was also decreased ONOO− release compared to statin alone (p < 0.01). Human umbilical vein ECs (HUVECs) were pretreated with 20 mg/dL oxLDL for 20 min, then treated with atorvastatin (active metabolite, ATM) and rosuvastatin (rosuva) at 1.0 μM ± EPA (10μM) for 1 hr. Cells were stimulated with calcium and assayed for the NO/ONOO− release ratio using nanosensors. ECs exposed to oxLDL showed a 60% reduction in NO release compared with vehicle (386±29 to 156±18 nM, p< 0.001) concomitant with a pronounced increase in ONOO− release (205±31 to 283±16 nM, p< 0.001), resulting in a >70% decrease in the NO/ONOO− release ratio (p < 0.001). ECs treated with ATM had an improved NO/ONOO− release ratio (53%) that increased in combination with EPA by 216% (p < 0.01). Similar results were observed for EPA in combination with rosuvastatin. When either statin was combined with EPA, there was also decreased ONOO− release compared to statin alone (p < 0.01). ConclusionIn combination with high intensity statins, EPA enhanced NO bioavailability in dysfunctional human ECs. The ability of EPA to reverse vascular EC dysfunction may lead to reduced ischemic events in statin-treated patients, as evidenced in outcome trials. In combination with high intensity statins, EPA enhanced NO bioavailability in dysfunctional human ECs. The ability of EPA to reverse vascular EC dysfunction may lead to reduced ischemic events in statin-treated patients, as evidenced in outcome trials.

EICOSAPENTAENOIC ACID (EPA) DECREASES CYTOKINE RELEASE AND EXPRESSION OF INFLAMMATORY AND PRO-THROMBOTIC PROTEINS IN BRAIN VASCULAR ENDOTHELIUM

Brain vascular endothelial cell (EC) dysfunction contributes to ischemic stroke due to inflammation and release of pro-thrombotic factors. Treatment with icosapent ethyl (IPE), the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid (EPA), reduced first and total ischemic strokes each by 36%, in statin-treated patients with elevated cardiovascular risk (REDUCE-IT). We tested the effects of EPA on cytokine release and expression of inflammatory proteins from brain microvascular ECs during inflammation.

Could Plasma CXCL12 Predict Ventricular Dysfunction in Patients with Severe Myocardial Infarction?

Plasma level of chemokine CXCL12 can predict adverse cardiovascular outcomes in patients with coronary artery disease, but data on its relationship with severity of coronary stenosis in cases of severe myocardial infarction (MI) are scarce and conflicting. The objective of this study was to investigate link between plasma CXCL12 levels and different grades of left ventricular ejection fraction (LVEF) in statin-treated and -untreated patients with severe MI. A total of 198 consecutive patients with first-time severe MI (ST-elevated myocardial infarction [STEMI], n = 121 and non-ST-elevated myocardial infarction [NSTEMI], n = 77) were recruited from Coronary Care Unit, King Abdulaziz University Hospital. They have one to two coronary arteries blocked ≥50%, or three arteries blocked 30 to 49%. Demographic and clinical criteria were collected and plasma CXCL12 level was measured. No correlations were detected between demographic and clinical criteria and CXCL12 level. While troponin peaks and LVEF significantly differed between STEMI and NSTEMI patients, CXCL12 level showed nonsignificant changes. Plasma CXCL12 levels decreased significantly in statin-treated patients compared with those untreated. From receiver operating characteristic (ROC) analysis, high CXCL12 levels were associated with no statin therapy. For STEMI and NSTEMI patients, area under the receiver operating characteristic curve for CXCL12 test were 0.685 and 0.820, while sensitivity and specificity values were 75.9 and 54.8%, and 73.1 and 84%, respectively. Plasma CXCL12 levels showed nonsignificant changes with different ranges of LVEF and troponin peaks. In patients with severe MI, irrespective of statin therapy, plasma CXCL12 showed no correlation with different ranges of LVEF suggesting that it cannot predict left ventricular dysfunction in these cases. However, cross-sectional design of this study is a limitation.

Remnant Cholesterol and the Risk of Coronary Artery Disease in Patients With Type 2 Diabetes.

Among statin-treated patients with type 2 diabetes mellitus (T2DM), there is still a great residual cardiovascular risk. Previous studies found that the level of remnant cholesterol (RC) could predict the coronary artery disease (CAD) risk. In the present study, we enrolled 4145 patients with T2DM; 2784 (67.2%) were male and their median age was 62years. After multivariate logistic analyses, plasma RC level was significantly and independently associated with CAD [odds ratio (OR) 13.524, 95% confidence interval (CI) = 7.058-25.912, P < .001) after adjustment for conventional risk factors, such as age, gender, hypertension, and other lipid levels. Even in the presence of high high-density lipoprotein cholesterol (HDL-C) level, the elevated RC could still predict CAD in T2DM patients (OR 2.064, 95%CI 1.438-2.964, P < .001). Furthermore, RC had relationships with age, hypertension, and smoking status in promoting CAD progression in T2DM patients, with all p for interactive <.001. In conclusion, RC level was independently associated with CAD risk in patients with T2DM.

Inflammation drives residual risk in chronic kidney disease: a CANTOS substudy.

Hyperlipidaemia and inflammation jointly contribute to atherosclerotic disease. Yet, after the initiation of statin therapy, the relative contributions of these processes may differ in patient groups, such as those with and without impaired kidney function. Among 9151 stable statin-treated post-myocardial infarction patients participating in the CANTOS trial, the contributions of residual cholesterol risk and residual inflammatory risk were evaluated as determinants of recurrent major adverse cardiovascular events (MACE) and total mortality, stratified by baseline estimated glomerular filtration rate (eGFR) above or below 60 mL/min/1.73 m2 using the race agnostic CKD-EPI 2021 formula (all participants had eGFR > 30 mL/min/1.73 m2). Analyses of residual inflammatory risk focused on high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) while analyses of residual cholesterol risk focused on LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C). Participants were followed for a period of up to 5 years (median 3.7 years). Median baseline levels of LDL-C and hsCRP were 81 mg/dL and 4.2 mg/L. Among participants with eGFR ≥ 60 mL/min/1.73 m2, increasing quartiles of plasma hsCRP, IL-6, LDL-C, and non-HDL-C all positively associated with risks of recurrent MACE [hazard ratios (HR) comparing the top to bottom quartile for hsCRP 1.45; for IL-6 2.48; for LDL-C 1.64; and for non-HDL-C 1.68] (all P < 0.0001). By contrast, among those with eGFR < 60 mL/min/1.73 m2, increasing quartiles of hsCRP and IL-6 significantly predicted recurrent MACE [HR comparing the top to bottom quartile for hsCRP 1.50 (P = 0.021); for IL-6 1.84 (P = 0.048)], whereas increasing quartiles of LDL-C and non-HDL-C did not [HR comparing the top to bottom quartile for LDL-C 1.04 (P = 0.80); for non-HDL-C 0.98 (P = 0.88)]. The predictive utility of hsCRP and IL-6 in the setting of eGFR < 60 mL/min/1.73 m2 remained significant after adjustment for a wide range of potential confounding factors including age, sex, smoking status, blood pressure, body mass index, and diabetes. For the endpoint of total mortality, both hsCRP (HR 1.77, P = 0.0021) and IL-6 (HR 2.15, P = 0.015) were significant predictors among those with eGFR < 60 mL/min/1.73 m2, whereas LDL-C (HR 0.91, P = 0.56) and non-HDL-C (HR 0.85, P = 0.31) were not. Similar effects were observed in analyses stratified by the albumin to creatinine ratio rather than eGFR. Among atherosclerosis patients with impaired kidney function already aggressively treated with statin therapy, residual inflammatory risk plays a substantial role in determining the risk of recurrent cardiovascular events. These data have implications for risk stratification of individuals with chronic kidney disease and for the development of novel agents that target inflammatory processes in this high-risk group of patients. ClinicalTrials.gov: NCT01327846.

Newer and Emerging LDL-C Lowering Agents and Implications for ASCVD Residual Risk.

Multiple lines of evidence demonstrate that low-density lipoprotein-cholesterol causes atherosclerotic cardiovascular disease. Thus, targeting and lowering low-density lipoprotein-cholesterol is the principal strategy to reduce cardiovascular disease risk in primary and secondary prevention. Statin therapy is the foundation of lipid-lowering treatment, but adherence rates are low, and many individuals do not attain target low-density lipoprotein-cholesterol values. Additionally, most statin-treated patients are still at considerable atherosclerotic cardiovascular disease risk, emphasizing the need for more aggressive low-density lipoprotein-cholesterol-lowering therapies. The purpose of this review is to discuss new and emerging approaches to further lower low-density lipoprotein-cholesterol, including inhibition of ATP-citrate lyase, proprotein convertase subtilisin-kexin type 9, angiopoietin-related protein 3, and cholesteryl ester transfer protein.

Eicosapentaenoic acid (EPA) increases detoxification proteins and reduces reactive oxygen species in pulmonary endothelial cells during exposure to urban air pollution

Background and Aims : Particulate matter (PM) in air pollution contributes to cardiovascular (CV) disease due to increased production of reactive oxygen species (ROS), such as peroxynitrite (ONOO-), in the pulmonary vasculature. Eicosapentaenoic acid (EPA) treatment reduced ischemic events in statin-treated patients with high CV risk (REDUCE-IT). We measured the effects of EPA on pulmonary endothelial cell (PEC) protein expression during exposure to urban pollutant PMs.

High-intensity statins combined with eicosapentaenoic acid (EPA) improves endothelial function during exposure to oxidized LDL

Background and Aims : Endothelial cell (EC) dysfunction leads to reduced nitric oxide (NO) bioavailability and increased cytotoxic peroxynitrite (ONOO−). Loss of NO promotes inflammation and impairs vasodilation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl (IPE) reduced cardiovascular (CV) events in statin-treated patients (REDUCE-IT). We tested the effects of high-intensity statins and EPA in ECs exposed to oxidized LDL (oxLDL).

Eicosapentaenoic acid (EPA) combined with high-intensity statins reduce lipid oxidation in model membranes compared to docosahexaenoic acid (DHA)

Background and Aims : Lipid oxidation leads to endothelial dysfunction and promotes foam cell formation during atherogenesis. Treatment with icosapent ethyl, a formulation of highly-purified omega-3 fatty acid (O3FA) EPA, reduced cardiovascular (CV) events in REDUCE-IT unlike trials using DHA-containing formulations in statin-treated patients. We compared the effects of EPA and DHA on lipid oxidation in membranes in combination with high-intensity statins.

Eicosapentaenoic acid (EPA) increased endothelial nitric oxide synthase (eNOS) levels and proteins associated with cellular responses to oxidative stress during inflammation

Background and Aims : Eicosapentaenoic acid (EPA) administered as icosapent ethyl (IPE) reduced cardiovascular (CV) ischemic events (REDUCE-IT) in contrast to trials using docosahexaenoic acid (DHA)-containing formulations in statin-treated patients. EPA improves endothelial cell (EC) function and nitric oxide (NO) bioavailability, features that may reduce atherothrombotic events. We measured the effects of EPA versus DHA on eNOS expression and coupling efficiency.