fimasartan + rosuvastatin (Tubero / Tuvero)

Persistent atherogenic lipoprotein changes during lorlatinib therapy.

Shibue Kimitaka K, Kunimasa Kei K, Hamasaki Akihiro A

Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK)/ROS1 tyrosine kinase inhibitor, frequently induces hypercholesterolemia and hypertriglyceridemia, but longitudinal qualitative lipoprotein changes remain incompletely characterized. We describe a 52-year-old woman with ALK-rearranged non-small cell lung cancer who developed persistent dyslipidemia despite lipid-lowering therapy. Before lorlatinib, total cholesterol was 164 mg/dL (SI [International System of Units]: 4.24 mmol/L) (reference range, 148-248 mg/dL [SI: 3.83-6.41 mmol/L]), low-density lipoprotein (LDL) cholesterol was 52 mg/dL (SI: 1.34 mmol/L) (reference range, 65-139 mg/dL [SI: 1.68-3.59 mmol/L]), and triglycerides were 54 mg/dL (SI: 0.61 mmol/L) (reference range, 30-117 mg/dL [SI: 0.34-1.32 mmol/L]). Within 3 weeks after lorlatinib initiation, these increased to 340, 245, and 166 mg/dL, respectively. Longitudinal profiling showed persistent apolipoprotein B (ApoB) elevation, increased oxidized LDL, and a prominent pre-β-lipoprotein fraction. Subclinical hypothyroidism was later detected, and pitavastatin was switched to rosuvastatin. This case highlights the potential value of ApoB and qualitative lipid assessment during prolonged lorlatinib therapy.

Interleukin-17D Deficiency Attenuates Atherosclerosis by Diminishing Macrophage Inflammation and Promoting M2 Phenotype.

Hou Jingyuan J, Gu Xiaodong X, Li Xia X, Zhao Junli J et al.

Macrophages are central to atherosclerosis by driving vascular inflammation, plaque growth, and instability. Although interleukin-17D (IL-17D) has been linked to endothelial inflammation, its role in macrophage-mediated atherosclerosis remains unclear. This study investigated the function and mechanism of macrophage IL-17D in atherosclerosis. Using IL-17D knockout, macrophage-specific IL-17D knockdown, and macrophage-specific Spi-B knockdown mouse models on an ApoE-/- background, we assessed aortic lesion burden, necrotic core formation, macrophage accumulation, inflammatory responses, and macrophage polarization. Mechanistic studies were performed using transcriptomic analysis, ChIP-PCR, and luciferase reporter assays. IL-17D deficiency markedly reduced atherosclerotic plaque formation in the whole aorta and aortic root, decreased necrotic core size, and limited macrophage accumulation and vascular inflammation. Both in vitro and in vivo, IL-17D deficiency promoted M2 macrophage polarization while suppressing pro-inflammatory cytokines and chemokines. Macrophage-specific IL-17D knockdown similarly attenuated atherosclerotic lesion development and inflammation. Mechanistically, IL-17D deficiency activated the Spi-B-STAT6 transcriptional axis. Macrophage-specific Spi-B knockdown reversed the anti-atherosclerotic effects of IL-17D deficiency, confirming its functional importance. Rosuvastatin suppressed IL-17D expression, and IL-17D repression contributed to its anti-inflammatory and anti-atherogenic effects. These findings identify macrophage-derived IL-17D as a key regulator of atherosclerosis. Targeting IL-17D may promote protective M2 polarization and alleviate vascular inflammation, offering a potential therapeutic strategy for atherosclerotic disease.

Potential triggers of drug-induced autoimmune-like hepatitis: aloe vera, rosuvastatin and the varicella zoster virus glycoprotein E antigen recombinant (Shingrix) vaccine.

Mishra Kritika K, Saxon Sarah S, Lynch Kate D KD

Association of serum complement levels with failure of low-density-lipoprotein-cholesterol target attainment in patients after acute coronary syndrome: A prospective, observational study.

Gogolas Vasileios V, Kyriazopoulou Evdoxia E, Dagre Anna A, Ikonomidis Ignatios I et al.

The interplay between inflammation and atherosclerosis is well acknowledged. However, the role of the complement system in lipid-lowering therapy (LLT) is poorly understood. To investigate the association of serum-complement levels with low-density lipoprotein cholesterol (LDL-C) levels in patients with acute coronary syndrome (ACS). Adult hospitalized patients with ACS received rosuvastatin 40 mg with an LDL-C target of <55 mg/dL and a reduction of >50% of baseline. High-sensitivity C-reactive protein, complement C3c, C4, C5a levels, LDL-C, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B levels were measured before treatment initiation, 6 weeks, 6 months, and 12 months afterward. Patients were followed up for 12 months for major adverse cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, cardiovascular death). Among 130 patients (91.5% male; mean age 56 ± 9 years), 42 (32.3%) achieved the target at 6 weeks, 61 (46.9%) at 6 months, and 63 (48.5%) at 12 months. Serum C3c levels were lower at baseline in 6-week target achievers (median [Q1-Q3], 98.9 [86.9-107.3]) vs nonachievers (126.0 [112.0-136.0]; P < .001). Similarly, C4 levels were 21.4 (18.2-26.4) mg/dL in achievers vs nonachievers (26.8 [22.1-31.6] mg/dL; P < .001); C5a levels did not differ between groups. C3c predicted failure of target attainment at 6 weeks (area under the curve, 95% CI: 0.94, 0.90-0.98; P < .001). A cut-off value of 112.5 mg/dL demonstrated sensitivity 77.3%, specificity 92.3%, and independently predicted failure (adjusted odds ratio 52.54; 95% CI, 12.49-221.0). In patients with ACS treated with rosuvastatin 40 mg, serum C3c levels are associated with failure of LDL-C target attainment. Further research is needed to determine if they may be used to guide LLT.