High-sensitivity C-reactive Protein Research Articles

Effect of Phytosterols on Serum Levels of C-Reactive Protein: A Time- and Dose-Response Meta-analysis of Randomized Controlled Trial.

Phytosterols are recognized for their cholesterol-reducing effects and are commonly used as dietary supplements or added to foods due to their potential cardiovascular benefits. However, evidence regarding the impact of phytosterol supplementation on inflammatory markers remains inconclusive. This systematic review and meta-analysis aim to evaluate the effect of phytosterols in reducing levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP). A systematic literature search of the primary databases was conducted up to May 2024 to identify eligible studies. The measurement of effect sizes was determined using WMD (weighted mean difference) and 95% CI. For the meta-analysis, 14 publications (19 study arms) for hs-CRP and 10 publications (16 study arms) for CRP were included. The pooled analysis showed that the administration of phytosterol did not significantly reduce CRP compared to control with WMD= -0.04mg/l (95% CI: -0.28 to 0.20, P = 0.74). However, phytosterol supplementation significantly decreased the hs-CRP level compared to the control group with WMD of -0.25mg/l (95% CI: -0.42 to -0.07, P = 0.006). The WMD for hs-CRP reduction was - 0.36mg/l (95% CI: -0.53 to -0.18, P < 0.001) for supplementation with a phytosterol dose ≥ 2000mg/day compared to the control group. Phytosterol supplementation may be effective in reducing hs-CRP levels.

Autologous platelet rich plasma injection can be effective in the management of osteoarthritis of the knee: impact on IL-1 β, TNF-α, hs-CRP

ObjectiveTo analyze the clinical efficacy of autologous platelet rich plasma (PRP) injection in the treatment of knee osteoarthritis (KOA) and its influence on related biomarkers such as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP).Method150 study subjects are randomly selected from KOA patients received treatment in the Third Hospital of Bethune Hospital from January 2022 to January 2023. After enrollment, patients are randomly numbered 1–100. 75 patients with odd and even numbers are included in the control group and the observation group, respectively. The former is cured with etocoxib, while the latter is treated with autologous PRP injection based on this. The clinical efficacy, relevant biomarkers (IL-1β, TNF-α, hs-CRP), and Lysholm knee score scale and Fugl Meyer assessment (FMA) scores are compared and analyzed.ResultsThe total effective rate of 94.67% (71/75) in the observation group was higher than 84.00% (63/75) in the other one group (P < 0.05). Before treatment, the comparison in IL-1β, TNF-α, hs-CRP, Lysholm knee joint score, and FMA scale score are with P > 0.05. When the treatment period is at 1 and 2 months, the IL-1β, TNF-α, hs-CRP levels within the group were lower than before treatment, while the Lysholm knee joint score and FMA scale score were higher than before treatment (P < 0.05). When the treatment period is at 1 and 2 months, the IL-1β, TNF-α, hs-CRP levels and the Lysholm knee joint and FMA scale scores in the observation group were lower and higher than those in the other one group, respectively (P < 0.05).ConclusionThe application of autologous PRP injection therapy in KOA patients can significantly improve their levels of related biomarkers, effectively improve knee joint function and motor function, and have good clinical efficacy.

Efficacy and safety of Danlou tablets in the treatment of stable angina pectoris with intermingled phlegm and blood stasis syndrome in coronary heart disease: a multicenter randomized controlled study

ObjectivesIn this study, we assessed the clinical efficacy and safety of Danlou tablets in the treatment of stable angina pectoris (SAP) with intermingled phlegm and blood stasis (IPBS), to provide high-quality evidence-based medical evidence for the prevention and treatment of coronary heart disease.MethodsIn this multicenter randomized controlled study, 304 patients diagnosed with stable angina pectoris with IPBS enrolled from 12 national traditional Chinese medicine (TCM) clinical research centers in China were randomly assigned to the treatment group and the control group at a ratio of 1:1. Each group was divided into four subgroups based on the results of TCM syndrome differentiation: IPBS, IPBS combined with qi deficiency, IPBS combined with qi stagnation, and IPBS combined with toxin accumulation. The control group was treated with routine Western medicine. In addition to routine Western medicine treatment, the treatment group (the IPBS group) was treated with Danlou tablets or Danlou tablets supplemented by interventional therapies based on the results of traditional Chinese medicine differentiation. The frequency of angina attacks per week was the main efficacy evaluation indicator and the secondary efficacy evaluation indicators included angina symptom score, Seattle Angina Questionnaire, an electrocardiogram (ECG) efficacy evaluation, a cardiac Doppler two-dimensional ultrasound, an electrocardiogram treadmill exercise test, blood lipids, blood glucose, a coagulation function test, hemorheology indicators, homocysteine, C-reactive protein (CRP) or high sensitivity-CRP, TCM syndromes (syndrome score, tongue, pulse), and long-term prognosis (endpoint outcome, cardiovascular events).ResultsThere were 300 cases in the full analysis set (FAS), 266 in the per-protocol set (PPS), and 300 in the safety set. Regarding the main efficacy indicator, after treatment, the reduction in the frequency of weekly angina attacks in the treatment group was significantly greater than that in the control group (P &amp;lt; 0.05). The results of the FAS and PPS were consistent. Regarding the secondary efficacy evaluation indicators, the angina symptom, TCM syndrome, ECG evaluation, Seattle Angina Pectoris Questionnaire, and 36-item Health Status Survey Summary Form scores of the treatment group were significantly higher than the control group (P &amp;lt; 0.05) and the homocysteine levels of the treatment group were significantly reduced (P &amp;lt; 0.05). The results of the FAS and PPS were consistent. In the PPS, the triglyceride levels in the treatment group were significantly lower than those in the control group after treatment (P &amp;lt; 0.05). The activated partial thromboplastin time in the treatment group decreased significantly (P &amp;lt; 0.05). There was no statistically significant difference in the safety indicators and incidence of adverse reactions between the two groups.ConclusionTreatment with Danlou tablets and the modified combination therapy based on Western medicine treatment could improve angina pectoris symptoms of patients with SAP and IPBS syndrome and its concurrent syndromes, and improve patients’ quality of life. Furthermore, the treatment is safe, has a long-term prognosis, and is worth further promotion and application in clinical practice.Clinical Trial Registrationhttps://www.chictr.org.cn/showprojEN.html?proj=235570, ChiCTR registry, ChiCTR1900023708.

Evaluation of a probiotic blend on psychosocial health and biomarkers of inflammatory, immune and stress response in adults with subthreshold depression: a double-blind, randomised, placebo-controlled trial.

This study examined the efficacy of a probiotic in reducing depressive symptom severity in people with subthreshold depression. In a double-blind, randomised, placebo-controlled trial, a probiotic (1 × 10^9 live cells per strain: Limosilactobacillus fermentum LF16 (DSM26956), Lacticaseibacillus rhamnosus LR06 (DSM21981), Lactiplantibacillus plantarum LP01 (LMG P-21021) and Bifidobacterium longum 04 (DSM23233)) or placebo was taken daily for 12 weeks. Data were collected at baseline, 6 and 12 weeks including psychological symptom severity (Beck Depression Inventory, BDI; Patient Health Questionnaire, PHQ; Hospital Anxiety Depression Scale, HADS; and Depression Anxiety and Stress Scale, DASS). Biomarkers of glycaemia, inflammation (high-sensitivity C-reactive protein, hs-CRP), antioxidant status (total glutathione (GSH)) and stress (cortisol awakening response, CAR) were also measured. Thirty-nine participants (nineteen probiotic;twenty placebo) were enrolled. There were no significant between-group differences in the examined psychological symptom severity scores, despite certain significant within-group changes observed in both groups from baseline to 6 and/or 12 weeks of follow-up. Regarding biomarkers, the probiotic group showed reduced hs-CRP (-1520; 95 % CI -273·7, -2766·2 ng/dl) and CAR (-0·28; 95 % CI -0·05, -0·51 μg/dl) at 12 weeks, but increased total GSH (3·9; 95 % CI 0·1, 7·5 ng/dl) at 6 weeks, compared with the placebo. The current study reported favourable decreases in depressive symptoms in both groups. Although the within-group changes observed in the probiotic group were supported by favourable inflammatory, antioxidant status and stress biomarker changes compared with the placebo, further research is required to shed more light on the role of gut microbiota modulation on emotional regulation.

High-sensitivity C-reactive protein is associated with cardiac dysfunction and morbidity in a community-based cohort

Abstract Background Inflammation is increasingly recognized as a risk factor for cardiac morbidity in the general population. Biomarkers like high-sensitivity C-reactive protein (hs-CRP) can aid in the detection of adverse systemic inflammation. The relationship between hs-CRP and cardiac structure and function is therefore a target of interest. Purpose The purpose of this study was to investigate the association of inflammation with cardiac structure and function in individuals free of overt cardiac disease. In addition, we examined if hs-CRP provided prognostic information regarding incident heart failure and myocardial infarction independent of echocardiographic measures. Methods In a community-based cohort study, participants were randomly selected for invitation from the Capital Region of Denmark. Echocardiography was performed on all the participants and measures of cardiac structure and function were obtained by blinded investigators. Participants with a history of cardiac disease were excluded from the analysis. Associations between log-transformed hs-CRP and echocardiographic measures were analyzed through uni- and multivariable linear regressions. Results A total of 3,379 individuals were included. Mean age was 55 years, 42% were female and the median hs-CRP was 1.13 (interquartile range: 0.65 - 1.47) mg/L. In the univariable analyses, increasing levels of hs-CRP were associated with worse left ventricular (LV) function including LV ejection fraction, global longitudinal strain (GLS), worse diastolic function (E/e’), worse right heart function (tricuspid regurgitation (TR) velocity and tricuspid annular plane systolic excursion (TAPSE)) and higher left ventricular (LV) mass index (p &amp;lt; 0.001 for all measures) (figure). When adjusting for sex, age, physical activity, smoking status, body mass index, blood pressure, hypercholesterolemia, diabetes, hypertension, creatinine, and heart rate, only LVEF (p &amp;lt; 0.001), GLS, (p &amp;lt; 0.001), E/e’ (p = 0.027), TAPSE (p = 0.008) and peak TR velocity (p = 0.015) remained significantly associated with increasing hs-CRP levels. In multivariable Cox regression adjusting for clinical characteristics and echocardiographic measures including LV ejection fraction, LV mass index, E/e’, TAPSE and GLS, higher hs-CRP was significantly associated with both heart failure and myocardial infarction (table) (HR for heart failure: 1.30, 95% CI: 1.03–1.66 p = 0.030; HR for acute myocardial infarction: 1.40, 95% CI: 1.04 – 1.89, p = 0.028, per doubling of hs-CRP). We did not find any interactions between hs-CRP and outcome among different types of echocardiographic phenotypes. Conclusion In the general population, higher levels of hs-CRP were associated with declining systolic, diastolic and right heart function. The associations persisted when adjusting for clinical characteristics. In addition, hs-CRP was associated with cardiac events independent of cardiac function as assessed by echocardiography.Linear regression splinesCox regressions

Effect of green coffee on miR-133a, miR-155 and inflammatory biomarkers in obese individuals

ObjectivesMetabolic syndrome is a cluster of conditions that increases the risk of atherosclerotic cardiovascular diseases. The current study was a randomized, double blind, placebo-controlled study that aimed to determine the impact of green coffee (GC) in obese patients with metabolic syndrome through analysis of miRNA-155, miRNA-133a and the inflammatory biomarkers such as resistin, TNF-α, total sialic acid, homocysteine, high sensitivity C-reactive protein (hs-CRP), and the anti-inflammatory cytokine, adiponectin.MethodsOne hundred-sixty obese patients were randomly supplemented either with GC capsules (800 mg) or placebo daily for six months. Both groups were advised to take a balanced diet. Blood samples were collected at baseline and after six months of supplementation.ResultsGC supplementation for 6 months reduced BMI (p = 0.002), waist circumference (p = 0.038), blood glucose (p = 0.002), HbA1c% (p = 0.000), Insulin (p = 0.000), systolic blood pressure (p = 0.005), diastolic BP (p = 0.001) compared with placebo. GC significantly decreased total cholesterol (TC, p = 0.000), LDL-C (p = 0.001), triglycerides (TG, p = 0.002) and increased HDL-C (p = 0.008) compared with placebo group. In addition, GC significantly (p ≤ 0.005) reduced total sialic acid, homocysteine, resistin, TNF-α, hs-CRP and the oxidative stress marker malondialdehyde (MDA), but increased serum adiponectin (p = 0.000) compared to placebo group. There was a significant reduction in the gene expression of miR-133a (p = 0.000) in GC group as compared with baseline levels and with the control placebo group (p = 0.001) after 6 months.ConclusionGC administration modulated metabolic syndrome by decreasing BMI, high BP, blood glucose, dyslipidemia, miRNA-133a and inflammatory biomarkers that constitute risk factors for cardiovascular diseases.ClinicalTrials.gov registration No. is NCT05688917.Graphical

Circulating Amyloid beta 1-40 is independently associated with statin treatment and LDL cholesterol reduction: a prospective cohort study

Abstract Background Accumulating evidence suggests that circulating amyloid beta 1-40 (Aβ40), a pro-inflammatory and pro-atherogenic peptide, is associated with atherosclerotic cardiovascular disease (ASCVD), providing incremental prognostic value and risk stratification refinement in primary and secondary prevention settings. Existing evidence supports conflicting off-target effects of statins on plasma Aβ40. We aim to explore the impact of cardiovascular risk reduction through statin therapy on Aβ40 plasma levels in subjects with dyslipidemia and with/without ASCVD. Methods In this prospective study, patients with dyslipidemia who visited for the first time our lipid clinic for risk stratification and treatment plan assessment (n=146) were consecutively recruited. Αβ40 was measured in plasma samples by enzyme-linked immunosorbent assay at baseline and after a mean follow-up of 5.2 and 15 months. Patients in whom statin treatment was initiated or intensified in terms of dose or regimen (n= 68) were compared against patients not treated with statins or with unchanged statin intensity (n = 78). Statin intensity treatment was defined based on the European Society of Cardiology (ESC) guidelines. Results Increased Aβ40 plasma levels at baseline were associated with ASCVD presence, decreased glomerular filtration rate (GFR), and history of heart failure (p&amp;lt;0.05 for all). An increase in Aβ40 circulating levels between baseline and follow-up 1 was observed in patients in whom statin treatment was initiated or intensified (p=0.041). However, in patients not treated with statins or treated with unchanged statin intensity, an increase in Aβ40 circulating levels was observed between follow-up 1 and follow-up 2 (p=0.05, Figure 1A). These changes in Aβ40 were significantly different between the two groups during the short follow-up period (β=0.226, p for interaction =0.025) independently from age and changes in GFR, systolic blood pressure, and LDL-C. Additionally, patients who achieved a reduction in low-density lipoprotein cholesterol (LDL-C) ≥ 50% in follow-up 2 have unchanged Aβ40 levels during the long follow-up period, while an increase in Aβ40 was observed in the rest population (p=0.012, Figure 1B). These changes were significantly different between the two LDL-C groups independently of statin treatment and changes in high sensitive C-reactive protein (hs-CRP) (β= -0.231, p for interaction=0.035). Conclusion In a dyslipidemic population, statin initiation or intensification and LDL-C decrease showed a short-term increase and a long-term return to initial levels, respectively, in circulating Aβ40 levels. From a mechanistic point of view, our findings suggest that statins have an impact on Aβ40, possibly through an LDL-C-dependent and a non-LDL-C-dependent pathway. Further studies are needed to evaluate the utility of circulating Aβ40 as a novel biomarker in ASCVD risk reduction assessment.

Awareness and perceptions of cardiologists towards systemic inflammation in atherosclerotic cardiovascular disease: A multi-national survey across 5 geographical regional sub-groups

Abstract Background Despite improvement in the management of atherosclerotic cardiovascular disease and chronic kidney disease (ASCVD+CKD), cardiovascular (CV) mortality remains unacceptably high. Evidence suggests that systemic inflammation (SI) is one of the key drivers for disease progression, yet clinical perceptions towards SI amongst cardiologists is poorly understood. Purpose FLAME-ASCVD (systemic inFLAMmation and rolE of hsCRP as a biomarker in AtheroSclerotic CardioVascular Disease) survey assessed cardiologist’s perceptions and awareness towards the role of SI and high sensitivity C-reactive protein (hsCRP) in patients (pts.) with ASCVD+CKD. Overall results were reported earlier1 and here we present results by sub-groups across 5 geographical regions. Methods This was a multinational, cross-sectional, online survey-based study conducted during March-May 2023. Eligible participants were cardiologists (interventional and general) who treated ≥15 ASCVD+CKD pts./month and practiced for ≥3 years. To minimize selection bias, specific study objective was not disclosed until eligibility criteria was met. An online questionnaire was used. Analysis included 5 sub-groups: Europe (EU: France, Germany, Italy, UK), Asia Pacific (AP: Australia, India), East Asia (EA: China, Japan), LatAm (LA: Brazil), Middle East (ME: Saudi Arabia). Descriptive statistics were used. Results Of the 1755 respondents, 602 eligible cardiologists (~60/country) completed the survey across the EU (n=241), AP (n=121), EA (n=120), LA (n=60), and ME (n=60). Hypertension, hyperlipidaemia, and lifestyle (diet/exercise) were consistently amongst the top 3-5 CV risk factors discussed with pts, across all regions. SI as a CV risk factor was discussed consistently less across regions (overall 10th at 43%, ³9th across regions, EU: 30%) (Table 1). Across regions, &amp;gt;70% of cardiologists acknowledged an intention to consider testing for SI, with the lowest being in the EU at 46%. Of those in the EU who did not consider testing, 53% (n=129) cited lack of medication as the reason. Across all regions, SI was consistently perceived as a risk factor for recurrent CV events (³65%) and residual inflammatory risk (47-85%), yet a noticeable proportion (52-92%) cardiologists acknowledged a need to learn more about SI in ASCVD+CKD (highest in ME, 92%). While overall (aided: 47% [n= 571]; unaided: 24%) considered hsCRP test for SI, few variations were observed (EA/AP/EU, aided: 55/52/33 and unaided: 22/24/03) (Table 2). Proven efficacy of hsCRP test, availability of medication for SI, and guideline recommendation were acknowledged as unmet needs to inform clinical care in ASCVD+CKD. Conclusion In this survey across regional sub-groups, discussion of SI as a CV risk factor was consistently low. Barring few noticeable variations in testing patterns in EU, perceptions towards SI were generally consistent. There is a need for better understanding and guidance on SI and hsCRP testing in practice.

The impact of cardiovascular risk factors on longitudinal changes in cardiac structure and function in an older population of hypertensive patients

Abstract Background Hypertension is associated with cardiac structural and functional changes, with left ventricular hypertrophy and diastolic dysfunction as strong predictors of adverse cardiac events. Limited data exist on how cardiovascular (CV) risk factors accelerate left ventricular (LV) mass and diastolic dysfunction over time in older hypertensive patients. Purpose To investigate the association between CV risk factors and accelerated deterioration of LV mass, left atrial volume (LAV), global longitudinal strain (GLS), and tissue Doppler E/e’ ratio in an older population of hypertensive patients. Methods Post-hoc analysis of a randomized clinical trial that investigated whether atrial fibrillation screening, using an implantable loop recorder, and subsequent initiation of anticoagulation, could prevent stroke in high-risk individuals. Only individuals with hypertension who had transthoracic echocardiography performed on two occasions, with a median of 5 years between echocardiograms, were included in this sub-study (n = 570). Multivariable linear regression analysis was performed to investigate the association between risk factors and changes in LV mass, LAV, GLS and E/e’. ß-values were calculated per 1 SD change for all variables. Results Mean age was 74±3 years, and 55% were men. Mean body mass index (BMI) was 27.8±4.3 kg/m2, 26% had diabetes, 58% used statins, 12% had a history of ischemic heart disease, and 4% had heart failure. The median use of antihypertensive drugs was 2 (IQR: 1,2), mean systolic blood pressure was 148.6±18.2 mmHg. During a median follow-up of 5 years, the mean increase in LV mass was 6.5±38.3g. Male sex (ß 0.24, p &amp;lt; 0.001) and increasing BMI (ß 0.29, p &amp;lt;0.001) were significantly associated with an accelerated increase in LV mass (Fig. 1). The mean increase in LAV was 14.6±15.7ml. Diabetes (ß -0.16, p = 0.006) and high sensitivity C-reactive protein (hsCRP) (ß 0.14, p = 0.007) were significantly associated with changes in LAV (Fig. 2). The absolute decline in mean GLS was 0.27%. Increasing age (ß -0.09, p = 0.027), heart failure (ß -0.10, p = 0.020), ischemic heart disease (ß -0.16, p &amp;lt; 0.001), hsCRP (ß -0.12, p = 0.003) and s-creatinine (ß -0.09, p = 0.033) were all significantly associated with an accelerated decline in GLS (Fig. 1). E/e’ declined with an average 0.96±2.89. Increasing age (ß 0.12, p = 0.001), female sex (ß 0.09, p = 0.049), and increasing systolic blood pressure (ß 0.13, p = 0.004) were associated with an increase in E/e’ (Fig. 2). Conclusion Male sex and increasing BMI were independently associated with an accelerated increase in LV mass. Diabetes was independently associated with LAV decline, while hsCRP was significantly associated with increasing LAV. Increasing age, heart failure, ischemic heart disease, hsCRP, and s-creatinine were independently associated with an accelerated decline in GLS. Increasing age, systolic blood pressure and female sex were independently associated with increasing E/e’.

Fat mass mediating effect on the association of worsening insulin resistance with increased left ventricular mass in 1595 adolescents: a 7-Year Longitudinal and Mediation Study

Abstract Background Fat mass-insulin resistance vicious cycle has been established in the young population and late adolescence has been identified as the critical time when the pathologic cycle begins. However, the independent and synergistic effect of fat mass in the relationship of insulin resistance with cardiac structure remains unexamined in a large cohort of adolescents, possibly due to the scarcity of repeated echocardiography measures. Mounting effective prevention strategies relies on strong evidence of the timing of the earliest cardiovascular alteration induced by insulin resistance. Purpose To investigate the longitudinal association of insulin resistance with left ventricular mass (LVM) and the mediating effect of fat mass in adolescents. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting glucose and insulin measured at 17- and 24-year clinic visits were included. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated from fasting insulin x fasting glucose/22.5 at ages 17 and 24 years. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7) was available at baseline and follow-up. Fat mass was repeatedly measured with dual-energy Xray absorptiometry at both time points. Multivariable adjusted association was examined using generalized linear mixed-effect models and adjusted for sex, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, and time-varying covariates measured at both baseline and follow-up such as age, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, fat mass, lean mass, smoking status, sedentary time, light physical activity, moderate-to-vigorous physical activity, low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol. Mediation analysis was conducted with a structural equation model adjusting for same covariates, except fat mass. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) median insulin resistance increased from 1.46 to 1.74, median fat mass increased from 15.6kg to 19.2kg and the mean LVMI increased from 35.4g/m2.7 to 38.1g/m2.7, over 7 years. In a fully adjusted model, increased insulin resistance from adolescence through young adulthood was significantly associated with increased LVMI (effect estimate 1.01g/m2.7 [95% CI, 0.63 – 1.57], p&amp;lt;0.001) across the 7-year observation period. Increased fat mass mediated (62.3% mediation effect) the longitudinal association between insulin resistance and LVMI from ages 17 – 24 years. Conclusion Worsening insulin resistance from adolescence through young adulthood was associated with increased cardiac mass, contributing 37% to the total increase in LVMI between ages 17 to 24 years but increased fat mass explained two-thirds of the relationship.

Interleukin-6 and suPAR improves prediction of all-cause mortality in type 1 diabetes - the Thousand &amp; 1 Study

Abstract Background Cardiovascular diseases (CVD) are the leading cause of mortality in type 1 diabetes (T1D). Inflammation frequently accompanies T1D and is suggested as an important contributor to the pathogenesis and progression of CVD. However, current risk prediction models for T1D lack biomarkers of inflammation. Methods A prospective study of individuals with T1D without overt heart disease was evaluated. Interleukin-6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) were analysed. In Cox proportional hazards model, adjustments were made for variables in the Steno T1 Risk Engine: age, sex, duration of diabetes, HbA1c, systolic blood pressure, glomerular filtration rate, albuminuria status, use of statins, tobacco use and physical activity. The model included the biomarkers as continuous variables, and a "combination" category was defined as simultaneously elevated suPAR &amp;gt; 4 ng/mL and IL-6 &amp;gt; 3 pg/mL. The net reclassification improvement (NRI) and C-statistics were calculated. Results For included individuals (n=1,014, 52% male, mean age 50±15), follow-up was 100% after median of 12.2 years (interquartile range: 11.8 to 12.9).In the fully adjusted model, IL-6 and suPAR were both associated with all-cause mortality (IL-6 hazard ratio (HR): 1.6 (95% confidence interval: 1.04 to 2.4), suPAR HR: 1.9 (1.2 to 2.9). HsCRP was not associated with the outcome. The combination category showed even stronger association: HR 2.7 (1.4 to 5.1). When added to the Steno T1 Risk Engine, IL-6, suPAR, and their combination all added discriminatory power in predicting all-cause mortality assessed by NRI; IL-6: 38% (19 to 58), suPAR: 45% (25 to 65), combination 56% (36 to 76). C-statistics showed similar results for only suPAR. Area under the curve for suPAR: from 0.84 to 0.86 (P=0.049), IL-6: 0.84 to 0.85 (P=0.338), combination: 0.84 to 0.86 (P=0.066). Conclusions IL-6 and suPAR are independently associated with all-cause mortality in T1D without known heart disease. Assessment of IL-6 and suPAR in T1D may enhance risk prediction.Figure 1Figure 2

Association of soluble ST2 with heart failure and other comorbidities in patients with severe coronary heart disease

Abstract Background Circulating levels of soluble suppression of tumorigenicity-2 (sST2) reflect vascular congestion, inflammation, and fibrosis. sST2 has been proposed as a useful biomarker to predict the mortality and hospitalization due to heart failure. However, there is limited evidence regarding the relationship between sST2 and heart failure, as well as other comorbidities, in severe coronary heart disease (CAD). Purpose This study aims to measure the circulating levels of soluble ST2 (sST2) in a large population of patients with severe CAD to determine its association with heart failure, cardiac function, inflammation, and other important comorbidities. Methods This subanalysis is part of the ongoing perspective observational study. Available serum samples from 520 patients undergoing elective coronary artery bypass grafting (CABG) were analysed for sST2 levels. The inclusion criteria were written informed consent and age between 18-85 years. Exclusion criteria for this analysis were severe valvular disease, severe chronic obstructive pulmonary disease, oxygen therapy, nocturnal positive airway pressure support or mechanical ventilation, and the need for catecholamines or circulatory assist devices. The circulating levels of human sST2 were measured from frozen serum (-80°C) using commercially available ELISA kits. The plasma was diluted 100 times to detect sST2 levels (assay range of 31.2 - 2,000 pg/mL). Two measurements were taken to account as means for intra-assay variabilities. Logarithmic transformation was used to convert non-normal distributed data. Student t' test and linear regression were applied to categorical or continuous variables as appropriate. Results sST2 levels (median 20.4 ng/ml, [IQR 15.5 – 28.8]) significantly predict worse left ventricular ejection fraction (β = -0.164, p = 0.006), and significantly correlate with levels of NT-proBNP (β = 3.263, p &amp;lt; 0.001), hs-Troponin T (β = 3.391, p &amp;lt; 0.001), high-sensitivity C-reactive protein (β = 2.472, p = 0.014) and heart failure (p= 0.002). Interestingly, common comorbidities such as chronic kidney disease (estimated glomerular filtration rate &amp;lt; 60 mL/min/1.73 m2, p = 0.004), diabetes mellitus (p = 0.001) and higher levels of glycated haemoglobin (HbA1c, β = 3.615, p &amp;lt; 0.001) showed also a significant association with sST2 levels. No significant association of sST2 was observed with arterial hypertension (p = 0.190), atrial fibrillation (p = 0.289), obesity (BMI ≥ 30 kg/m2, p = 0.302), sleep apnoea (apnoea-hypopnoea index ≥ 15/h, p = 0.068), peripheral artery disease (p = 0.823), or previous stroke (p = 0.861). Conclusion(s) Circulating levels of sST2 significantly correlate with heart failure, NT-proBNP, hs-TnT, and hs-CRP in patients with severe CAD. Additionally, sST2 levels were found to be elevated in patients with diabetes mellitus and chronic kidney disease.

The association of inflammation, triglycerides and lipoprotein(a) with cardiovascular events in the UK Biobank

Abstract Background Recent trial data has suggested that high-sensitivity C-reactive protein (hsCRP) is, at least, as strong a predictor of future cardiovascular events as LDL cholesterol in patients on lipid-lowering therapy1,2. There are limited data however on how hsCRP and other additional risk factors perform in patients at different levels of CVD risk. Purpose To evaluate the relationship of hsCRP, triglyceride and lipoprotein(a) [Lp(a)] levels with cardiovascular events in guideline-defined, clinically distinct cohorts. Such a study will improve the understanding of CVD risk prediction and provide essential information on the role of these pathways in CVD. Methods Data from the UK Biobank were used. In accordance with the 2021 ESC CVD prevention guidelines, four risk groups were derived based on clinical data and 10-year CVD risk, calculated from the recently derived SCORE2 model (Figure 1)3. Those not falling into one of the four cohorts were excluded as further risk stratification in these individuals would not influence management. For increasing quartiles (Q) of each biomarker, hazard ratios (HR), 95% confidence intervals (CI) and p-values were calculated relative to the lowest Q, using Cox proportional hazards models, adjusted for age, sex, smoking status, systolic blood pressure, HDL cholesterol and total cholesterol. Interactions between sex and biomarker were explored. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, and ischaemic stroke. Secondary endpoints were the individual components of the primary endpoint. Results A total of 229,339 participants were included across the four risk groups, with a total of 24,133 primary endpoint events over the mean follow-up period of 14 years. In all four groups there was a robust linear relationship of hsCRP with MACE (p&amp;lt;0.001 [Figure2]) – strongest in the secondary prevention population (Q4 v Q1 HR=1.79 [95%CI:1.60, 2.02]). Of the secondary endpoints, hsCRP was most strongly associated with cardiovascular death (Q4 v Q1 secondary prevention cohort HR=1.97 [1.68, 2.30]). Lp(a) was associated with MACE in the primary prevention cohorts only (Q4 vs Q1 high-risk cohort HR=1.35 [1.27, 1.44]), driven by its strong association with myocardial infarction (Q4 vs Q1 HR 1.61 [1.48, 1.75]) but not other secondary endpoints. After adjustment, triglyceride levels were not associated with MACE in the four cohorts. There was no evidence of sex interactions in any analysis (p&amp;gt;0.05). Conclusions After adjustment for traditional CVD risk factors, hsCRP is a more robust predictor of cardiovascular events than Lp(a) or triglycerides in both primary and secondary prevention settings. Consideration should be given to evaluating whether hsCRP, Lp(a) and other ‘non-traditional’ risk factors can improve CVD risk reclassification and/or be used to guide allocation to targeted anti-atherosclerotic therapies.Figure 1:Participant FlowFigure 2:Main effects

Long-term prognostic value of multiple circulating biomarkers for ventricular arrhythmias in patients with left ventricular hypertrabeculation

Abstract Background Left ventricular hypertrabeculation (LVHT) is a rare morphologic phenotype of the heart with heterogeneous manifestations and variable prognosis [1,2]. Ventricular arrhythmia (VA) has been recognized as an independent risk factor that significantly impacts the mortality of LVHT patients [1,3]. However, knowledge regarding the prognosis and risk stratification of VAs in LVHT is currently limited. Purpose To explore the long-term predictive value of multiple circulating biomarkers reflecting cardiac function, endothelial function, inflammation, and oxidative stress for the development of VAs in LVHT patients. Methods This longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2012 and December 2020 at a national-level medical center. All participants possessed thorough profiles of multiple biomarkers [N-terminal pro-brain natriuretic peptide, big endothelin-1 (big ET-1), high-sensitivity C-reactive protein, uric acid and free fatty acid] and had no previously documented ventricular arrhythmic events. The cohort were followed annually until October 2022. VA was defined as a composite of non-sustained ventricular tachycardia, sustained ventricular tachycardia, ventricular fibrillation, and appropriate therapy of implantable cardioverter defibrillator. Potential predictors for VAs in the LVHT cohort were evaluated by multivariable Cox regression. Restricted cubic spline (RCS) analysis was employed to explore the nonlinear association between plasma big ET-1 and clinical outcomes. Differences in the cumulative incidence of VAs according to big ET-1 levels and/or the extent of hypertrabeculation were analyzed by Kaplan-Meier curves. Results A total of 265 morphologically diagnosed LVHT patients (44.2 ± 17.0 years, 65.7% male) were included in this study. Over a median follow-up of 4.34 years, 82 (30.9%) patients experienced ventricular arrhythmic events. Multivariable Cox regression analysis identified that baseline levels of big ET-1 (hazard ratio 1.513, 95% confidence interval 1.136-2.013) and isolated hypertrabeculation in left ventricular lateral wall (LVLW) (hazard ratio 1.810, 95% confidence interval 1.023-3.202) were independently associated with the occurrence of VAs. RCS analysis illustrated that the susceptibility to VAs was remarkably raised with the increase of big ET-1 levels. LVHT patients with higher plasma big ET-1 suffered from more severe cardiac dysfunction and remodeling. Individuals who displayed elevated concentrations of big ET-1 and isolated LVLW hypertrabeculation were at a significantly greater risk of developing VAs. Conclusions Introducing routine assessments for plasma big ET-1 and the extent of hypertrabeculation at baseline can offer valuable support in the risk stratification and clinical management of ventricular arrhythmic events in patients with LVHT.Prognositc value of big ET-1 for VAsbig ET-1/LVLW hypertrabeculation &amp; VAs

HIV is associated with subtle impairments in left ventricular function: insights from a large prospective cohort study of well-treated people with HIV

Abstract Background Human Immunodeficiency Virus (HIV) has become a treatable, chronic condition, but people with HIV still face an elevated risk of cardiovascular disease, including heart failure. Purpose To assess echocardiographic alterations in left ventricular (LV) function in a contemporary cohort of well-treated people with HIV compared to the general population. Methods We included 744 people with HIV frequency matched 1:1 on age and sex with controls from the general population. Both people with HIV and controls underwent echocardiography, physical examination, questionnaires and blood sampling according to similar study protocols. LV systolic dysfunction was defined as LV ejection fraction (LVEF) &amp;lt;50% or absolute global longitudinal strain (GLS) &amp;lt;16%. LV diastolic function was defined as abnormal if the following was true for half or more available parameters: (1) average E/e’&amp;gt;14, (2) septal e’ velocity &amp;lt; 7 cm/s or lateral e’ velocity &amp;lt;10cm/s, (3) tricuspid regurgitation velocity &amp;gt;2.8 m/s, (4) left atrial volume index &amp;gt;34ml/m2. Associations between HIV status and LV function were assessed using linear and logistic regression models adjusted for age, sex, smoking, hypertension, diabetes mellitus, total cholesterol and high-sensitivity C-reactive protein. Among people with HIV, the association between HIV-specific characteristics and LV function were assessed using logistic regression models with adjustment for the same potential confounders. Results Mean age was 53.4 years and 88% were male. For people with HIV, median time since HIV diagnosis was 18 years and 99% received antiretroviral therapy. People with HIV had lower adjusted mean absolute GLS [17.6 vs. 18.5%, p&amp;lt;0.001], E/A ratio [1.0 vs. 1.2, p&amp;lt;0.001] and average e’ [9.5 vs. 10.5 cm/s, p&amp;lt;0.001] than controls, while LVEF and E/e’ were not significantly different between people with HIV and controls (Figure 1). HIV was associated with impaired systolic function as assessed by GLS [odds ratio 1.70, 95% CI: 1.17-2.46, p=0.005], but not when assessed by LVEF [odds ratio 1.06, 95% CI: 0.78-1.45, p=0.69](Figure 2). Living with HIV was not associated with diastolic dysfunction compared to controls [odds ratio 0.97, 95% CI: 0.61-1.52, p=0.88], but longer HIV-duration was associated with higher odds of diastolic dysfunction among people with HIV (odds ratio 1.06, 95% CI: 1.02-1.10 per year, p=0.004). Current antiretroviral medication type, previous AIDS defining conditions, current CD4+ count and detectable viral load were not associated with LV dysfunction. Conclusion People with HIV show signs of early impairments in longitudinal LV systolic function compared to the general population. These subclinical changes may underlie the increased risk of heart failure observed in PWH.

Increased circulating levels of standardized inflammatory and endothelial dysfunction biomarkers in patients with myocardial infarction with nonobstructive coronary arteries

Abstract Introduction Around 10% of patients with acute myocardial infarction (AMI) present with nonobstructive coronary arteries (MINOCA), for which the underlying pathophysiology is often uncertain. Our aim was to evaluate inflammatory burden and endothelial dysfunction in MINOCA patients by assessing biomarkers in both acute and stable phases. Methods An analytical and observational study at a University Hospital involving 166 MI patients admitted over the past 3years. Following ESC guidelines, patients were categorized into MINOCA or myocardial infarction with significant coronary artery disease (MI-CAD) groups. Circulating levels of inflammatory biomarkers (interleukin-6(IL-6), tumor necrosis factor-α(TNF-α) and high-sensitivity C-reactive protein(hs-CRP)) and of endothelial dysfunction (asymmetric dimethylarginine (ADMA)) were measured in 44 MINOCA patients and 122 MI-CAD patients at acute phase (admission and discharge) and stable phase (2months after MI). As biomarker levels may vary with MI size, each value was standardized by dividing it by the peak troponin, resulting in a biomarker/troponinT ratio. We evaluated the effects of standardized (SB) and non-standardized (NSB) biomarker values using a multivariate regression model adjusted for age and sex. Results We analyzed 166 patients (median age:68 years, 70% males). MI-CAD patients had higher peak high-sensitive troponinT (hs-TnT) levels upon admission compared to those with MINOCA (1491ng/L vs 247ng/L,p&amp;lt;0.001),likely due to larger infarctions generating higher levels of inflammation. When examining the association between infarct size, as measured by peak hs-TnT values, and biomarker levels, we observed a significant dose-response relationship for hs-CRP at admission (βcoefficient 0.16 [95%CI,0.02-0.29],p0.02) and IL-6 at admission (βcoefficient 0.15 [95%CI,0.04-0.27],p0.01). Significant positive associations were found between MINOCA and all SBs, both during the acute phase and in follow-up. During the acute phase ORs ranged from 1.35to2.7 (p&amp;lt;0.05) for inflammatory biomarkers and from 2.34 to 2.76 (p&amp;lt;0.01) for ADMA. In the stable phase ORs ranged from 1.49to3.06 (p&amp;lt;0.05) for inflammatory biomarkers, and OR was 2.79(p&amp;lt;0.01) for ADMA (Figure 1). In contrast, none of the NSBs were associated with MINOCA. Regarding temporal biomarker changes, during the acute phase of MI and 2 months post-event, both MINOCA and MI-CAD patients showed similar trends. However, MINOCA patients consistently maintained elevated inflammatory activity and ADMA concentrations only when biomarkers were standardized by infarct size (Figure 2). Conclusions Higher levels of SBs were consistently associated with MINOCA, both during the acute phase of the event and in follow-up, compared to MI-CAD. Consequently, this study suggests that the inflammatory burden, measured by heightened levels of standardized inflammatory biomarkers, and endothelial dysfunction, as measured by ADMA, may play a role in the pathophysiology of MINOCA.Boxplots for SBs at three time points.Temporal changes in biomarker levels.

Control for multiple risk factors and incident heart failure and mortality in patients with diabetes mellitus: insights from the kailuan cohort study

Abstract Purpose This study aimed to evaluate the relationship between control for multiple risk factors and diabetes-related heart failure and all-cause mortality, and to explore the extent to which the excess risk can be reduced. Methods Diabetes participants with pre-existing heart failure documented in discharge register or medical insurance records and incomplete baseline risk factor information were excluded. Each of these patients was then matched randomly to four control subjects. The degree of risk factor control was defined by attainment of target values for blood pressure, body mass index , low-density lipoprotein cholesterol, fasting blood glucose, high-sensitive C-reactive protein and smoking. The primary outcome was newly diagnosed heart failure, and the secondary outcome was all-cause mortality.Fine-Gray and Cox regression were performed to estimate the risk of heart failure and all-cause mortality among diabetes patients in relation to the degree of control for multiple risk factors respectively, and the group with ≤1 risk factor control was set as the reference group. All-cause mortality was used as a competing risk in the Fine-Gray model. Results A total of 17,676 patients with diabetes and 69,493 matched non-diabetic control subjects were included. Of these, 84.2% were men and the mean age was 56.2±10.7 years. Over a median follow-up of 11.2 (13.1-15.0) years, a total of 1,070 cases of heart failure and 4,121 cases of all-cause mortality were identified among patients with diabetes. Significant inverse associations were observed between the number of well-controlled risk factors and the risk of incident adverse outcomes in diabetes patients. For each additional risk factor that was controlled, there was an associated 16% decrease in the risk of heart failure and a 10% decrease in the risk of all-cause mortality. The incidence rate of heart failure among diabetes patients was at its lowest for those with ≥5 risk factors (HR: 0.46, 95% CI: 0.34-0.62), and it constantly increased with a lower number of well-controlled risk factors. As for all-cause mortality, the lowest risk was associated with optimal risk factor control (HR: 0.59, 95% CI: 0.50-0.68). Among diabetes patients with ≥5 risk factors that were well controlled, the adjusted hazard ratio for heart failure and all-cause mortality was 1.25 (95%CI: 0.99-1.56) and 1.17(95%CI: 1.05-1.31) respectively, as compared with controls. The protective impact of comprehensive risk factor control on the risk of heart failure was more pronounced among men than women, as well as among those using antihypertensive medications than non-users. Conclusions Control for multiple risk factors is related to a lower risk of heart failure and all-cause mortality in an accumulative and sex-specific manner. Compared to the general population, patients with diabetes mellitus remains associated with an increased risk for the outcomes in spite of the optimization of risk factor control.

Clinical impact of systemic inflammation across the spectrum of different high-sensitivity CRP values in patients undergoing percutaneous coronary intervention

Abstract Background Systemic inflammation enhances atherosclerosis progression and is a well-established determinant of cardiovascular risk. High-sensitivity C-reactive protein (hsCRP), the most widely available biomarker of inflammation, has indeed been associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). However, some heterogeneity exists in the threshold to define high hsCRP associated with increased cardiovascular risk, with the 2 and 3 mg/L cut-offs being used more commonly. Purpose We aimed to evaluate the clinical impact of systemic inflammation in patients undergoing PCI across the spectrum of baseline hsCRP values. Methods We retrospectively evaluated consecutive patients undergoing PCI with drug-eluting stent implantation from 2012 to 2022 at Mount Sinai Hospital (NY, USA). We excluded patients presenting with acute myocardial infarction or active cancer and those for whom baseline hsCRP was not available or was above 10 mg/L. Patients were stratified into three groups according to baseline hsCRP levels: &amp;lt;2.0, 2.0 to 3.0, and &amp;gt;3.0 mg/L. We estimated the risk of 12-month adverse events using the lowest hsCRP group (&amp;lt;2.0 mg/L) as reference. The primary endpoint was MACCE, defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACCE individual components, target vessel revascularization (TVR), stent thrombosis and bleeding. Results A total of 10,811 patients were included in the analysis. Of these, 6,210 (57.4%) had hsCRP &amp;lt;2.0 mg/L, 1,624 (15.0%) between 2 and 3 mg/L and 2,977 (27.6%) &amp;gt;3.0 mg/L. Incidence of anemia, diabetes mellitus, peripheral and cerebrovascular artery disease, atrial fibrillation and chronic kidney disease increased stepwise across hsCRP groups. Moreover, patients with higher hsCRP tended to present more frequently with unstable angina and higher baseline LDL cholesterol levels. As regards procedural variables, coronary artery disease severity and PCI complexity did not differ significantly across groups. When compared with patients with hsCRP &amp;lt; 2, hsCRP &amp;gt; 3 mg/L was associated with a greater adjusted risk of MACCE (4.9% vs 2.4%; HR 1.75 % CI 1.35 - 2.28), all-cause death (2.5% vs 0.9%, HR 2.34, 95%CI 1.57-3.47) and MI (2.5% vs 1.3%; HR 1.58 95%CI 1.11-2.26) (Figure 1). Risks of stroke, TVR, stent thrombosis and bleeding did not significantly differ across hsCRP groups (Table 1) Conclusions In patients undergoing PCI, elevated hsCRP values exceeding 3 mg/L exhibit a more robust association with the risk of MACCE and all-cause mortality, as compared with both hsCRP &amp;lt; 2.0 and between 2.0 and 3.0 mg/L. In this context, the use of hsCRP might improve the stratification of patients associated with higher inflammatory burden.

Exploratory mediation analysis of the effect of semaglutide on cardiovascular outcomes in people with overweight or obesity in the SELECT randomised trial

Abstract Background Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to reduce major adverse cardiovascular (CV) events (MACE) in people with diabetes. The SELECT trial investigated weekly subcutaneous semaglutide 2.4 mg versus placebo in people with pre-existing CV disease and body mass index ≥27kg/m², but without diabetes at randomisation. Over a mean duration of follow-up of 39.8 months, risk of MACE was lower in patients treated with semaglutide vs placebo (6.5% vs 8.0%, hazard ratio, 0.80; 95% CI, 0.72, 0.90; P&amp;lt;0.001). There were improvements in several CV risk factors; however, mechanisms underlying the MACE reduction are unclear. Purpose This prespecified analysis explored whether the effects on measured CV risk factors may mediate the 20% reduction in MACE in SELECT. Methods CV risk factors measured during the trial and included as potential mediators in the analysis were: body weight, waist circumference, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c), lipids, blood pressure, estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Mediation analyses were performed using the Vansteelandt repeated regression approach. First, the observed difference in MACE-free survival between semaglutide and placebo at 36 months was estimated as the total effect. The direct effect of semaglutide was then estimated as the difference in MACE-free survival, had the semaglutide arm experienced the values of the mediator observed in the placebo arm during follow-up. The % mediation was then calculated as 100 × (1 – [direct effect] / [total effect]). A reversed counterfactual approach estimating the direct effect as the difference between arms in MACE-free survival, had the placebo arm experienced the mediator values observed in the semaglutide arm, was also conducted. A large disparity between the % mediation from the two approaches can indicate potential treatment–mediator interaction or hidden confounding. Results Statistically significant (P&amp;lt;0.05) improvements in all potential mediators were observed with semaglutide. Table 1 shows the estimated mediation of each potential mediator when evaluated separately. Point estimates for the % mediation were largest for waist circumference (64.0%), hsCRP (42.1%), HbA1c (29.0%) and body weight (19.5%), but with wide 95% CIs. For waist circumference, the estimated mediation was markedly lower using the reversed counterfactual approach, suggesting potential hidden confounding or treatment–mediator interaction (Figure 1). In a multivariable analysis, the estimated joint mediation was 31.4% (−30.1%, 143.6%). Conclusions The results suggest that neither change in body weight nor other measured CV risk factors fully explain the effect of semaglutide on MACE in SELECT. Substantial unmeasured pleiotropic effects of semaglutide on MACE not mediated through these risk factors remain possible.

Clinical outcomes according to residual cholesterol and inflammatory risk in patients undergoing PCI

Abstract Background Elevated concentrations of low-density lipoprotein cholesterol (LDL-c) and low grade vascular inflammation, commonly quantified using high-sensitivity C-reactive protein (hsCRP), have been demonstrated to be causal in the development of atherosclerotic disease. Whilst recent large-scale trials have investigated the relative impact of LDL-c and inflammation on cardiovascular outcomes, there is a scarcity of data in real-world patients undergoing percutaneous coronary intervention (PCI). Purpose To investigate the relative drivers of residual risk in patients with established statin treatment undergoing PCI in a contemporary large-scale cohort. Methods From January 2012 to February 2020 patients undergoing PCI at a tertiary center were included for current analysis. Patients were categorized into 4 subgroups according to different combinations of LDL-c and hsCRP concentrations at baseline: no residual cholesterol or inflammatory risk (LDL-c &amp;lt;70 mg/dL + hsCRP &amp;lt;2 mg/L), residual cholesterol risk (LDL-c ≥70 mg/dL + hsCRP &amp;lt;2 mg/L), residual inflammatory risk (LDL-c &amp;lt;70 mg/dL + hsCRP ≥2 mg/L), and combined residual cholesterol and inflammatory risk (LDL-c ≥70 mg/dL + hsCRP ≥2 mg/L). Individuals who presented with acute myocardial infarction, neoplastic disease and hsCRP concentrations &amp;gt;10 mg/l were excluded. The outcome of interest was major adverse cardiac events (MACE - composite of all-cause mortality, myocardial infarction, or stroke). A univariable cox regression model was calculated. Results Overall, 10,845 patients were included. In total, 3,210 patients displayed neither cholesterol nor inflammatory risk and 3,059 individuals had elevated cholesterol risk only. In 1,839 patients an inflammatory risk was noted, whilst 2,737 patients presented with combined cholesterol and inflammatory risk. Kaplan-Meier curves for 1-year follow-up are displayed in Figure 1. Patients with residual inflammatory risk had the highest event rate of the composite endpoint (5.2%), followed by patients with combined residual risk (3.5%), individuals with residual cholesterol risk (2.3%) and persons with neither cholesterol nor inflammatory risk (2.4%; p&amp;lt;0.0001 for log rank test across all groups). An association with MACE was solely documented for patients with residual inflammatory risk (HR: 2.09, 95% CI: 1.52 - 2.88; p&amp;lt;.001), and also borderline significant for combined cholesterol and inflammatory risk (HR: 1.41, 95% CI: 1.03 - 1.95; p=0.034), whilst this was not the case for patients with elevated cholesterol risk only (see Figure 2). Conclusion In a contemporary real-world cohort of statin treated patients undergoing PCI, inflammation irrespective of LDL-c concentrations was the driver for adverse cardiovascular outcomes. This data might be helpful to further define target populations for both intensified lipid-lowering as well as anti-inflammatory treatment approaches.