Lipoprotein(a) (Lp(a)) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Our goal was to characterize patients undergoing Lp(a) testing and to assess the impact of Lp(a) testing on treatment changes and subsequent ASCVD events. A cross-sectional and a longitudinal claims data analysis were performed on 4 million patient records in Germany. Patients were followed up for a maximum of 4 years. In 2015 and 2018, 0.25% and 0.34% of patients were tested, respectively. Testing was more frequent in younger women in the overall population, and in men in the ASCVD population. Patients tested for Lp(a) had more comorbidities and higher ASCVD risk compared to matched control patients. ASCVD hospitalizations were more frequent prior to the first Lp(a) test (5.55 vs 1.42 per 100/person-years). The mortality rate of the Lp(a)-tested cohort and the control group was similar. Mortality was lower in patients with prior ASCVD and Lp(a) testing compared to matched controls with prior ASCVD and no Lp(a) test (2.30 vs 3.64 per 100/person-years, p <0.001). Patients with Lp(a) test received more laboratory examinations and cardiovascular medications and had more visits with specialized physicians. Lp(a) testing is rarely performed even in patients with very high cardiovascular risk. Patients tested for Lp(a) have more comorbidities and a higher ASCVD risk. Lp(a) testing is associated with more intensive preventive treatment and with positive effects on clinical outcomes and survival. The data support the value of Lp(a) measurements to characterize ASCVD risk and to improve ASCVD prevention.

Lipodystrophy syndromes (LDs) are characterized by loss of adipose tissue, metabolic complications such as dyslipidemia, insulin resistance, and fatty liver disease, as well as accelerated atherosclerosis. As a result of adipose tissue deficiency, the systemic concentration of the adipokine leptin is reduced. A current promising therapeutic option for patients with LD is treatment with recombinant leptin (metreleptin), resulting in reduced risk of mortality. Here, we investigate the effects of leptin on endothelial to mesenchymal transition (EndMT), which impair the functional properties of endothelial cells and promotes atherogenesis in LD. Leptin treatment reduced inflammation and TGF-β2–induced expression of mesenchymal genes and prevented impairment of endothelial barrier function. Treatment of lipodystrophic- and atherosclerosis-prone animals (Ldlr ^−/− ; aP2-nSrebp1c-Tg) with leptin reduced macrophage accumulation in atherosclerotic lesions, vascular plaque protrusion, and the number of endothelial cells with mesenchymal gene expression, confirming a reduction in EndMT in LD after leptin treatment. Treatment with leptin inhibited LD-mediated induction of the proatherosclerotic cytokine growth/differentiation factor 15 ( GDF15 ). Inhibition of GDF15 reduced EndMT induction triggered by plasma from patients with LD. Our study reveals that in addition to the effects on adipose tissue function, leptin treatment exerts beneficial effects protecting endothelial function and identity in LD by reducing GDF15 .

Statin intolerance is associated with increased cardiovascular risk. Symptoms and patients’ characteristics are incompletely known. We aimed to analyse the health-related quality of life (QOL) associated with statin intolerance. The Statin Intolerance Registry (SIR) is an observational, prospective, multicentre study that included 1111 patients, with intolerance to at least two different statins, between 2021 and 2023 in Germany. SIR baseline data were compared to individuals with and without statin therapy of the population-based LIFE-Adult Study (n = 9983). The mean age in SIR was 66.1 years (standard deviation (SD) 9.9). The cohort was characterized by a higher proportion of women compared to patients on statins in LIFE-Adult (57.7% vs. 38.2%). SIR patients had impaired QOL (mean EQ VAS score of 64.9 (SD 18.1)) as measured by EuroQol (EQ-5D-5L)), which further deteriorated with age. Muscle symptoms were frequent (95.8%) and were associated with severe pain in 43.2% and intake of pain medication in 32.3% of statin intolerant patients. 10.3% had a diagnosis of depression. Women reported more pronounced symptoms than men. A data-driven k-means analysis, based on variables predicting severity of pain while on statin therapy, identified five clusters of SIR patients. The clusters differed in sex, prevalence of depression, QOL, comorbidities, and expectations to tolerate statin therapy. Statin intolerance is associated with impaired QOL. Women are more frequently and severely affected. The identified clusters may help to identify patients at risk and to develop individualized strategies to improve patient trajectories and outcomes. 10.13039/501100008678 Leipzig University , research grants from Daiichi Sankyo, Novartis, and Amgen to 10.13039/501100008678 Leipzig University .

Background: Lipoprotein(a) (Lp(a)) is an inherited risk factor for atherosclerotic cardiovascular disease (ASCVD). Limited data exist on Lp(a) values in children. We aimed to evaluate whether Lp(a) concentrations in youth are influenced by BMI. Methods: 756 blood samples of 248 children with obesity and 264 matched healthy children aged 5 and 18 years, enrolled in the population-based LIFE Child (German civilization diseases cohort) study, were analyzed. Repeat measurements were available in 154 children (1–4 follow ups, ~1 year apart). Results: The median Lp(a) concentration in the total cohort (n = 512) at first visit was 9.7 mg/dL (IQR 4.0–28.3). Lp(a) concentrations between 30–50 mg/dL were observed in 11.5%, while 12.5% exhibited Lp(a) ≧50 mg/dL. There was no association of Lp(a) with body mass index (BMI) (ß = 0.004, P = 0.49). Lp(a) levels did not correlate with age or sex, while Lp(a) was associated positively with low-density lipoprotein cholesterol (ß = 0.05, P < 0.0001). The Lp(a) risk category remained stable in 94% of all children in repeated measurements. Conclusions: The data showed no association of Lp(a) levels in children with BMI, age or sex. Measurement of Lp(a) in youth may be useful to identify children at increased lifetime risk for ASCVD. Impact: In youth, Lp(a) levels are not affected by age, sex and BMI. Lp(a) risk categories remain stable over time in repeated measurements in children. Measurement of Lp(a) in children may be useful as an additional factor to identify children at increased lifetime risk for ASCVD and for reverse family screening.

Statin intolerance (SI) is an important cause of insufficient low-density lipoprotein cholesterol (LDL-C) target attainment. Contemporary treatment strategies and symptoms in patients with SI are incompletely understood. We report baseline lipid-lowering therapies (LLTs) and LDL-C target attainment in the Statin Intolerance Registry, an observational, prospective, multicenter study that recruited 1,111 patients with SI between 2021 and 2023 in Germany. The mean age was 66.1 (SD 9.9) years, 57.7 % were female. At study inclusion, 83.1 % received at least one LLT, and 47.0 % received combination LLT. A higher number of LLTs was associated with lower LDL-C, lower systolic blood pressure, more atherosclerotic disease, more elevations of creatine kinase and liver enzymes but not with impaired quality of life as measured by EuroQol (EQ-5D-5L). PCSK9 inhibitors were most frequently prescribed (48.0 %), followed by ezetimibe (39.2 %), statins (26.9 %), most commonly rosuvastatin, and bempedoic acid (25.4 %). Patients who had been prescribed multiple statins before were more likely to take a statin at baseline. Patients on a statin, even at low intensity, had lower LDL-C levels compared to patients without statin therapy (mean [SD] 2.4 [1.2] vs. 2.9 [1.6] mmol/L, p < 0.001). Significantly more men than women achieved the LDL-C target (21.7 % vs. 11.4 %, p < 0.001, total cohort: 15.8 %). LDL-C target attainment is low in patients with SI, especially among women, despite high cardiovascular risk. The use of a greater number of LLTs, including statins, is not associated with reduced quality of life but is associated with lower LDL-C levels.

Zusammenfassung: Einleitung Die ESC/EAS-Leitlinien von 2019 zum Dyslipidämie-Management empfehlen LDL-Cholesterin (LDL-C) Zielwerte gemäß dem kardiovaskulären (CV) Risiko des Patienten. SANTORINI untersucht als erste große europäische Beobachtungsstudie seit Einführung der Leitlinien 2019, ob sich das Lipidmanagement von Patienten mit hohem und sehr hohem CV Risiko verbessert hat. Methoden SANTORINI ist eine multinationale Registerstudie an 9602 Patienten ≥ 18 Jahre mit hohem und sehr hohem CV Risiko, die eine lipidsenkende Therapie benötigen. Primäres Ziel der Studie ist die Dokumentation der Effektivität aktueller Behandlungsstrategien zum LDL-C-Management in der täglichen Praxis. Ergebnisse Für diese Analyse lagen vollständige Baselinedaten für 2086 Patienten in Deutschland und 6958 Patienten in Europa vor. Die CV Risikoklassifizierung durch die Behandler erfolgte bei > 50 % der Patienten auf Basis der ESC/EAS-Leitlinien von 2019 und ergab ein hohes CV Risiko für 15,6 % (173/1112) bzw. ein sehr hohes CV Risiko für 84,4 % (939/1112) der Patienten in Deutschland (Europa: 20,7 % [743/3594] hohes, 79,3 % [2851/3594] sehr hohes CV Risiko). Eine unabhängige Nachberechnung, basierend auf diesen Guidelines, ergab dagegen ein hohes bzw. sehr hohes CV Risiko für 4,1 % (46/1112) bzw. 94,5 % (1051/1112) der Patienten in Deutschland. Auch im europäischen Vergleich wurde das CV Risiko in ca. 10 % der Fälle unterschätzt.Zu Studienbeginn erhielten 59,5 % (1241/2086) der Patienten in Deutschland und 52,6 % (3661/6958) der Patienten in Europa eine lipidsenkende Monotherapie und 19,9 % (416/2086, Deutschland) bzw. 25,2 % (1753/6958, Europa) eine Kombinationstherapie. 78,6 % (1640/2086) der Patienten in Deutschland verfehlten die in den ESC/EAS-Leitlinien empfohlenen LDL-C-Zielwerte (Europa: 71,7 % [4989/6958]). Fazit Die ESC/EAS Leitlinien-Empfehlungen von 2019 werden nur bei einer Minderheit der Patienten umgesetzt. Die Studie identifiziert Chancen zur Verbesserung der Prävention von CV Erkrankungen in Deutschland.