Three-year changes in high-sensitivity cardiac troponin-T and total mortality in older adults.

Elevated high-sensitivity cardiac troponin-T (hs-cTnT) is associated with mortality in older adults. However, little is known about the implications of changes over time. We investigated hs-cTnT 3-year change and its association with subsequent mortality in the Activity and Function in the Elderly Study.

Subphenotypes of adult-onset diabetes: Data-driven clustering in the population-based KORA cohort.

Aims: A data-driven cluster analysis in a cohort of European individuals with type 2 diabetes (T2D) has previously identified four subgroups based on clinical characteristics. In the current study, we performed a comprehensive statistical assessment to (1) replicate the above-mentioned original clusters; (2) derive de novo T2D subphenotypes in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) cohort and (3) describe underlying genetic risk and diabetes complications.

Methods: We used data from n = 301 individuals with T2D from KORA FF4 study (Southern Germany).

Effects of Inclisiran in Patients With Atherosclerotic Cardiovascular Disease: A Pooled Analysis of the ORION-10 and ORION-11 Randomized Trials.

Objective: To evaluate the efficacy, safety, and tolerability of inclisiran in participants with atherosclerotic cardiovascular disease (ASCVD) from ORION-10 and ORION-11 stratified by key patient characteristics.

Patients And Methods: Participants were randomized 1:1 to receive 300 mg inclisiran sodium (284 mg inclisiran) or placebo on days 1, 90, 270, and 450, alongside background lipid-lowering therapy. This pooled, post hoc analysis stratified participants with ASCVD by sex, age, race, kidney function, body mass index, and glycemic status.

Familial Hypercholesterolemia: Pitfalls and Challenges in Diagnosis and Treatment.

Familial hypercholesterolemia (FH), a condition, which is characterized by a life-long exposure to markedly elevated low-density lipoprotein (LDL) concentrations from birth, and it still remains underdiagnosed and undertreated, despite the fact that its heterogeneous form represents one of the commonest genetic disorders to date. Indeed, only 10% of all estimated affected individuals have been diagnosed worldwide and for the most of them diagnosis comes too late, when atherosclerotic cardiovascular disease (ASCVD) has already been developed. Undiagnosed and undertreated FH leads to accelerated ASCVD with a high rate of premature deaths.

Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease.

Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities.

Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDL) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events.

Methods: Among 68,748 CHD-free subjects at baseline LDL was calculated as "LDL-C-Lp(a)-C," where Lp(a)-C was 30% or 17.

Associations between multiple neurological biomarkers and distal sensorimotor polyneuropathy: KORA F4/FF4 study.

Aims: The aim of this study was to assess associations between neurological biomarkers and distal sensorimotor polyneuropathy (DSPN).

Materials And Methods: Cross-sectional analyses were based on 1032 participants aged 61-82 years from the population-based KORA F4 survey, 177 of whom had DSPN at baseline. The prevalence of type 2 diabetes was 20%.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.

Background And Aims: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis.

Prediction of Myocardial Infarction Using a Combined Generative Adversarial Network Model and Feature-Enhanced Loss Function.

Accurate risk prediction for myocardial infarction (MI) is crucial for preventive strategies, given its significant impact on global mortality and morbidity. Here, we propose a novel deep-learning approach to enhance the prediction of incident MI cases by incorporating metabolomics alongside clinical risk factors. We utilized data from the KORA cohort, including the baseline S4 and follow-up F4 studies, consisting of 1454 participants without prior history of MI.

Inclisiran in individuals with diabetes or obesity: Post hoc pooled analyses of the ORION-9, ORION-10 and ORION-11 Phase 3 randomized trials.

Aims: To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata.

Materials And Methods: Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3-month doses up to 18 months, with background oral lipid-lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m).

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.

Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.

Design, Setting, And Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age.

Estimating potential cardiovascular health benefits of improved population level control of LDL cholesterol through a twice-yearly siRNA-based approach: A simulation study of a health-system level intervention.

Background And Aims: Inclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation.

Methods: For each participant in the ORION-10 and ORION-11 trials comparing inclisiran with placebo, baseline 10-year cardiovascular risk was estimated using the SMART equation.

PCSK9 inhibition with orally administered NNC0385-0434 in hypercholesterolaemia: a randomised, double-blind, placebo-controlled and active-controlled phase 2 trial.

Background: Currently available injectable drugs that target proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce serum LDL cholesterol and improve cardiovascular outcomes. This phase 2 study assessed NNC0385-0434, an oral PCSK9 inhibitor, in individuals receiving oral lipid-lowering therapy.

Methods: In this randomised, double-blind, placebo-controlled and active-controlled trial, 42 research sites across seven countries (Belgium, Germany, Greece, Japan, the Netherlands, Poland, and the USA) recruited individuals with established atherosclerotic cardiovascular disease (aged ≥40 years) or at high risk of atherosclerotic cardiovascular disease (aged >50 years), who had LDL cholesterol concentration of at least 1·8 mmol/L and were receiving maximum tolerated statins and stable lipid-lowering therapy.

Association of plasma proteomics with incident coronary heart disease in individuals with and without type 2 diabetes: results from the population-based KORA study.

Background: Coronary heart disease (CHD) is a major global health concern, especially among individuals with type 2 diabetes (T2D). Given the crucial role of proteins in various biological processes, this study aimed to elucidate the aetiological role and predictive performance of protein biomarkers on incident CHD in individuals with and without T2D.

Methods: The discovery cohort included 1492 participants from the Cooperative Health Research in the Region of Augsburg (KORA) S4 study with 147 incident CHD cases (45 vs.

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease: the BiomarCaRE project.

Background And Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.

Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.

Low-Dose Colchicine in Patients With Type 2 Diabetes and Recent Myocardial Infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

Objective: The cardiovascular benefits of low-dose colchicine have been demonstrated in patients with coronary disease. Its effects were evaluated in this prespecified analysis in patients with type 2 diabetes (T2D) from the Colchicine Cardiovascular Outcomes Trial (COLCOT).

Research Design And Methods: COLCOT was a randomized, double-blinded trial of colchicine, 0.

Proteogenomic Data Integration Reveals CXCL10 as a Potentially Downstream Causal Mediator for IL-6 Signaling on Atherosclerosis.

Background: Genetic and experimental studies support a causal involvement of IL-6 (interleukin-6) signaling in atheroprogression. Although trials targeting IL-6 signaling are underway, any benefits must be balanced against an impaired host immune response. Dissecting the mechanisms that mediate the effects of IL-6 signaling on atherosclerosis could offer insights about novel drug targets with more specific effects.

Long-term exposure to ambient air pollution and inflammatory response in the KORA study.

Previous studies consistently showed an association between fine atmospheric particulate matter (PM) and cardiovascular diseases. Concerns about adverse health effects of ultrafine particles (UFP) are growing but long-term studies are still scarce. In this study, we examined the association between long-term exposure to ambient air pollutants and blood biomarkers of inflammation and coagulation, including fibrinogen, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) adiponectin and interleukin-6 (IL-6), measured in the German KORA-S4 cohort study (1999-2001).