Estimated sdLDL-C for predicting high-risk coronary plaque features in psoriasis: a prospective observational study.

BACKGROUND: Psoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive. METHODS: A recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C. RESULTS: Estimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (ß = 0.37; P = 0.050) and LDL-C adjustment for FFB (ß = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C. CONCLUSIONS: Estimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifiers: NCT01778569.

Substitution pattern in ruthenium octa-n-butoxyphthalocyanine complexes influence their reactivity in N-H carbene insertions.

Ruthenium phthalocyanine complexes bearing n-OBu substituents in the peripheral or non-peripheral positions are efficient catalysts for the selective double or single carbene insertion to the amine N-H bonds. This complementary reactivity of two Ru complexes can be used for the synthesis of asymmetric tertiary amines and diamines bearing different substituents and has been demonstrated by two examples of readily available primary amines using different carbene precursors in successive reactions.

Updates in the Impact of Chronic Systemic Inflammation on Vascular Inflammation by Positron Emission Tomography (PET).

PURPOSE OF REVIEW: In this review, we focus on the clinical and epidemiological studies pertaining to systemic and vascular inflammation by positron emission tomography (PET) in patients with chronic inflammatory conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and psoriasis to highlight the importance of chronic systemic inflammation on vascular inflammation by PET in these disease states. RECENT FINDINGS: Recent clinical and translation advancements have demonstrated the durable relationship between chronic systemic inflammation and cardiovascular disease (CVD). In chronic inflammatory states, this relationship is robustly evident in the form of increased vascular inflammation, yet traditional risk estimates often underestimate the subclinical cardiovascular risk conferred by chronic inflammation. PET has emerged as a novel, non-invasive imaging modality capable of both quantifying the degree of systemic and vascular inflammation and detecting residual inflammation prior to cardiovascular events. We begin by demonstrating the role of inflammation in the pathogenesis of atherosclerosis, discussing how PET has been utilized to measure systemic and vascular inflammation and their effect on subclinical atherosclerosis, and finally reviewing recent applications of PET in constructing improved risk stratification for patients at high risk for stroke and CVD.

COVID-19-Associated dyslipidemia: Implications for mechanism of impaired resolution and novel therapeutic approaches.

The current coronavirus disease 2019 (COVID-19) pandemic presents a global challenge for managing acutely ill patients and complications from viral infection. Systemic inflammation accompanied by a "cytokine storm," hemostasis alterations and severe vasculitis have all been reported to occur with COVID-19, and emerging evidence suggests that dysregulation of lipid transport may contribute to some of these complications. Here, we aim to summarize the current understanding of the potential mechanisms related to COVID-19 dyslipidemia and propose possible adjunctive type therapeutic approaches that modulate lipids and lipoproteins. Specifically, we hypothesize that changes in the quantity and composition of high-density lipoprotein (HDL) that occurs with COVID-19 can significantly decrease the anti-inflammatory and anti-oxidative functions of HDL and could contribute to pulmonary inflammation. Furthermore, we propose that lipoproteins with oxidized phospholipids and fatty acids could lead to virus-associated organ damage via overactivation of innate immune scavenger receptors. Restoring lipoprotein function with ApoA-I raising agents or blocking relevant scavenger receptors with neutralizing antibodies could, therefore, be of value in the treatment of COVID-19. Finally, we discuss the role of omega-3 fatty acids transported by lipoproteins in generating specialized proresolving mediators and how together with anti-inflammatory drugs, they could decrease inflammation and thrombotic complications associated with COVID-19.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Effects of CYP2C19*17 Genetic Polymorphisms on the Steady-State Concentration of Diazepam in Patients With Alcohol Withdrawal Syndrome.

Background: Diazepam is one of the most widely prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS), which includes the symptoms of anxiety, fear, and emotional tension. However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions, reducing the efficacy of therapy. Aim: The purpose of our study was to investigate the effects of CYP2C19*17 genetic polymorphisms on the steady-state concentration of diazepam in patients with AWS. Materials and Methods: The study was conducted on 50 Russian male patients suffering from the AWS. For the therapy of psychomotor agitation, anxiety, fear, and emotional tension, patients received diazepam in injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time polymerase chain reaction. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions. Therapeutic drug monitoring (TDM) was performed using the high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Results: Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 -806C>T genotypes: (*1/*1) -12.0 [-15.0; -8.0], (*1/*17+*17/*17) -7.0 [-14.0; -5.0], P < .001, as well as the results of TDM: (CC) 250.70 [213.34; 308.53] ng/mL (*1/*17+*17/*17) 89.12 [53.26; 178.07] ng/mL, P < .001. Conclusion: Thus, our study enrolling 50 patients with AWS, showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant difference in the levels of plasma steady-state concentrations of diazepam in patients carrying different genotypes.

Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis.

RATIONALE: Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis. OBJECTIVE: To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis. METHODS AND RESULTS: Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P <0.05 for all) with significant association of oxidized LDL (ß=0.10; P=0.020) and oxHDL (ß=-0.11; P=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32; P=0.03). CONCLUSIONS: Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.

Comparative Study of the Electronic Structures of µ-Oxo, µ-Nitrido, and µ-Carbido Diiron Octapropylporphyrazine Complexes and Their Catalytic Activity in Cyclopropanation of Olefins.

The electronic structure of three single-atom bridged diiron octapropylporphyrazine complexes (FePzPr8)2X having Fe(III)-O-Fe(III), Fe(III)-N-Fe(IV) and Fe(IV)-C-Fe(IV) structural units was investigated by Mössbauer spectroscopy and density functional theory (DFT) calculations. In this series, the isomer shift values decrease, whereas the values of quadrupole splitting become progressively greater indicating the increase of covalency of Fe-X bond in the µ-oxo, µ-nitrido, µ-carbido row. The Mössbauer data point to low-spin systems for the three complexes, and calculated data with B3LYP-D3 show a singlet state for µ-oxo and µ-carbido and a doublet state for µ-nitrido complexes. An excellent agreement was obtained between B3LYP-D3 optimized geometries and X-ray structural data. Among (FePzPr8)2X complexes, µ-oxo diiron species showed a higher reactivity in the cyclopropanation of styrene by ethyl diazoacetate to afford a 95% product yield with 0.1 mol % catalyst loading. A detailed DFT study allowed to get insight into electronic structure of binuclear carbene species and to confirm their involvement into carbene transfer reactions.

Properties and reactivity of µ-nitrido-bridged dimetal porphyrinoid complexes: how does ruthenium compare to iron?

Methane hydroxylation by metal-oxo oxidants is one of the Holy Grails in biomimetic and biotechnological chemistry. The only enzymes known to perform this reaction in Nature are iron-containing soluble methane monooxygenase and copper-containing particulate methane monooxygenase. Furthermore, few biomimetic iron-containing oxidants have been designed that can hydroxylate methane efficiently. Recent studies reported that µ-nitrido-bridged diiron(IV)-oxo porphyrin and phthalocyanine complexes hydroxylate methane to methanol efficiently. To find out whether the reaction rates are enhanced by replacing iron by ruthenium, we performed a detailed computational study. Our work shows that the µ-nitrido-bridged diruthenium(IV)-oxo reacts with methane via hydrogen atom abstraction barriers that are considerably lower in energy (by about 5 kcal mol‒1) as compared to the analogous diiron(IV)-oxo complex. An analysis of the electronic structure implicates similar spin and charge distributions for the diiron(IV)-oxo and diruthenium(IV)-oxo complexes, but the strength of the O‒H bond formed during the reaction is much stronger for the latter. As such a larger hydrogen atom abstraction driving force for the Ru complex than for the Fe complex is found, which should result in higher reactivity in the oxidation of methane.

Mechanism of Oxidative Activation of Fluorinated Aromatic Compounds by N-Bridged Diiron-Phthalocyanine: What Determines the Reactivity?

The biodegradation of compounds with C-F bonds is challenging due to the fact that these bonds are stronger than the C-H bond in methane. In this work, results on the unprecedented reactivity of a biomimetic model complex that contains an N-bridged diiron-phthalocyanine are presented; this model complex is shown to react with perfluorinated arenes under addition of H2 O2 effectively. To get mechanistic insight into this unusual reactivity, detailed density functional theory calculations on the mechanism of C6 F6 activation by an iron(IV)-oxo active species of the N-bridged diiron phthalocyanine system were performed. Our studies show that the reaction proceeds through a rate-determining electrophilic C-O addition reaction followed by a 1,2-fluoride shift to give the ketone product, which can further rearrange to the phenol. A thermochemical analysis shows that the weakest C-F bond is the aliphatic C-F bond in the ketone intermediate. The oxidative defluorination of perfluoroaromatics is demonstrated to proceed through a completely different mechanism compared to that of aromatic C-H hydroxylation by iron(IV)-oxo intermediates such as cytochrome P450 Compound I.

Bioinspired Oxidation of Methane in the Confined Spaces of Molecular Cages.

Non-heme iron, vanadium, and copper complexes bearing hemicryptophane cavities were evaluated in the oxidation of methane in water by hydrogen peroxide. According to 1H nuclear magnetic resonance studies, a hydrophobic hemicryptophane cage accommodates a methane molecule in the proximity of the oxidizing site, leading to an improvement in the efficiency and selectivity for CH3OH and CH3OOH compared to those of the analogous complexes devoid of a hemicryptophane cage. While copper complexes showed low catalytic efficiency, their vanadium and iron counterparts exhibited higher turnover numbers, ≤13.2 and ≤9.2, respectively, providing target primary oxidation products (CH3OH and CH3OOH) as well as over-oxidation products (HCHO and HCOOH). In the case of caged vanadium complexes, the confinement effect was found to improve either the selectivity for CH3OH and CH3OOH (≤15%) or the catalytic efficiency. The confined space of the hydrophobic pocket of iron-based supramolecular complexes plays a significant role in the improvement of both the selectivity (≤27% for CH3OH and CH3OOH) and the turnover number of methane oxidation. These results indicate that the supramolecular approach is a promising strategy for the development of efficient and selective bioinspired catalysts for the mild oxidation of methane to methanol.

µ-Nitrido Diiron Macrocyclic Platform: Particular Structure for Particular Catalysis.

The ultimate objective of bioinspired catalysis is the development of efficient and clean chemical processes. Cytochrome P450 and soluble methane monooxygenase enzymes efficiently catalyze many challenging reactions. Extensive research has been performed to mimic their exciting chemistry, aiming to create efficient chemical catalysts for functionalization of strong C-H bonds. Two current biomimetic approaches are based on (i) mononuclear metal porphyrin-like complexes and (ii) iron and diiron non-heme complexes. However, biomimetic catalysts capable of oxidizing CH4 are still to be created. In the search for powerful oxidizing catalysts, we have recently proposed a new bioinspired strategy using N-bridged diiron phthalocyanine and porphyrin complexes. This platform is particularly suitable for stabilization of Fe(IV)Fe(IV) complexes and can be useful to generate high-valent oxidizing active species. Indeed, the possibility of charge delocalization on two iron centers, two macrocyclic ligands, and the nitrogen bridge makes possible the activation of H2O2 and peracids. The ultrahigh-valent diiron-oxo species (L)Fe(IV)-N-Fe(IV)(L(+•))═O (L = porphyrin or phthalocyanine) have been prepared at low temperatures and characterized by cryospray MS, UV-vis, EPR, and Mössbauer techniques. The highly electrophilic (L)Fe(IV)-N-Fe(IV)(L(+•))═O species exhibit remarkable reactivity. In this Account, we describe the catalytic applications of µ-nitrido diiron complexes in the oxidation of methane and benzene, in the transformation of aromatic C-F bonds under oxidative conditions, in oxidative dechlorination, and in the formation of C-C bonds. Importantly, all of these reactions can be performed under mild and clean conditions with high conversions and turnover numbers. µ-Nitrido diiron species retain their binuclear structure during catalysis and show the same mechanistic features (e.g., (18)O labeling, formation of benzene epoxide, and NIH shift in aromatic oxidation) as the enzymes operating via high-valent iron-oxo species. µ-Nitrido diiron complexes can react with perfluorinated aromatics under oxidative conditions, while the strongest oxidizing enzymes cannot. Advanced spectroscopic, labeling, and reactivity studies have confirmed the involvement of high-valent diiron-oxo species in these catalytic reactions. Computational studies have shed light on the origin of the remarkable catalytic properties, distinguishing the Fe-N-Fe scaffold from Fe-C-Fe and Fe-O-Fe analogues. X-ray absorption and emission spectroscopies assisted with DFT calculations allow deeper insight into the electronic structure of these particular complexes. Besides the novel chemistry involved, iron phthalocyanines are cheap and readily available in bulk quantities, suggesting high application potential. A variety of macrocyclic ligands can be used in combination with different transition metals to accommodate M-N-M platform and to tune their electronic and catalytic properties. The structural simplicity and flexibility of µ-nitrido dimers make them promising catalysts for many challenging reactions.

Association of matrix metalloproteinase 3 and γ-glutamyltransferase 1 gene polymorphisms with the cardio-ankle vascular index in young Russians.

Specific gene polymorphisms are known to be associated with a different arterial physiology in the younger generation. The present study found that young Russians with the matrix metalloproteinase 3 6A/6A and γ-glutamyltransferase 1AA genotypes have lower levels of the cardio-ankle vascular index - a recent measure of arterial stiffness. This observation may serve as an additional tool for cardiovascular disease prevention in the young population.

Antioxidant-related gene polymorphisms associated with the cardio-ankle vascular index in young Russians.

The cardio-ankle vascular index is a measure of arterial stiffness, whereas oxidative stress underlies arterial pathology. This study aimed to investigate the association between the cardio-ankle vascular index and antioxidant-related gene polymorphisms in young Russians. A total of 89 patients (mean age, 21.6 years) were examined by the cardio-ankle vascular index and for 15 gene polymorphisms related to antioxidant enzymes including FMO3 (flavin-containing monooxygenase 3), GPX1 (glutathione peroxidase 1), and GPX4 (glutathione peroxidase 4). A higher cardio-ankle vascular index level was detected in carriers with the KK-genotype of FMO3 polymorphism rs2266782 than in those without (mean levels: 6.2 versus 5.6, respectively, p<0.05). Similarly, a higher cardio-ankle vascular index level was seen in carriers with the CC-genotype of GPX4 polymorphism rs713041 than in those without (6.0 versus 5.5, respectively, p<0.05). We did not observe significant associations between the cardio-ankle vascular index levels and the other gene polymorphisms. Although carriers with the LL-genotype of GPX1 polymorphism rs1050450 showed a higher diastolic blood pressure level than those without, the polymorphism did not affect the cardio-ankle vascular index level. This study showed a significant association between rs2266782 and rs713041 polymorphisms and arterial stiffness, as measured by the cardio-ankle vascular index, in young Russians. The pathways utilised by antioxidant enzymes may be responsible for early arterial stiffening in the Russian population.

Catalytic defluorination of perfluorinated aromatics under oxidative conditions using N-bridged diiron phthalocyanine.

Carbon-fluorine bonds are the strongest single bonds in organic chemistry, making activation and cleavage usually associated with organometallic and reductive approaches particularly difficult. We describe here an efficient defluorination of poly- and perfluorinated aromatics under oxidative conditions catalyzed by the µ-nitrido diiron phthalocyanine complex [(Pc)Fe(III)(µ-N)Fe(IV)(Pc)] under mild conditions (hydrogen peroxide as the oxidant, near-ambient temperatures). The reaction proceeds via the formation of a high-valent diiron phthalocyanine radical cation complex with fluoride axial ligands, [(Pc)(F)Fe(IV)(µ-N)Fe(IV)(F)(Pc(+•))], which was isolated and characterized by UV-vis, EPR, (19)F NMR, Fe K-edge EXAFS, XANES, and Kß X-ray emission spectroscopy, ESI-MS, and electrochemical techniques. A wide range of per- and polyfluorinated aromatics (21 examples), including C6F6, C6F5CF3, C6F5CN, and C6F5NO2, were defluorinated with high conversions and high turnover numbers. [(Pc)Fe(III)(µ-N)Fe(IV)(Pc)] immobilized on a carbon support showed increased catalytic activity in heterogeneous defluorination in water, providing up to 4825 C-F cleavages per catalyst molecule. The µ-nitrido diiron structure is essential for the oxidative defluorination. Intramolecular competitive reactions using C6F3Cl3 and C6F3H3 probes indicated preferential transformation of C-F bonds with respect to C-Cl and C-H bonds. On the basis of the available data, mechanistic issues of this unusual reactivity are discussed and a tentative mechanism of defluorination under oxidative conditions is proposed.

X-ray absorption and emission spectroscopies of X-bridged diiron phthalocyanine complexes (FePc)2X (X = C, N, O) combined with DFT study of (FePc)2X and their high-valent diiron oxo complexes.

µ-Nitrido diiron phthalocyanine [PcFe(+3.5)NFe(+3.5)Pc](0) is an efficient catalyst, able to catalyze the oxidation of methane under near-ambient conditions. In this work, we compared the properties of structurally similar µ-carbido (1), µ-nitrido (2), and µ-oxo (3) dimers of iron phthalocyanine. The goal was to discern the structural and electronic differences between these complexes and to propose a rationale for the exceptional activity of 2. Extended X-ray fine-structure spectroscopy, high-resolution X-ray emission spectroscopy, and resonant inelastic X-ray scattering were applied to study the geometry and electronic structure of iron species in the series 1-3. The data provided by core hole spectroscopies were compared to the results of DFT calculations and found to coherently describe the structural and electronic properties of 1-3 as having equivalent iron centers with formal iron oxidation degrees of 3, 3.5, and 4 for the µ-oxo, µ-nitrido, and µ-carbido dimers, respectively. However, the bond length to the bringing atom changed in an unexpected sequence Fe-O > Fe-N < Fe-C, indicating redox non-innocence of the brigding µ-carbido ligand in 1. According to the X-ray emission spectroscopy, the µ-nitrido dimer 2 is a low-spin compound, with the highest covalency in the series 1-3. The DFT-calculated geometry and electronic structures as well as core hole spectra of hypothetical high-valent oxo complexes of 1-3 were compared, in order to explain the particular catalytic activity of 2 and to estimate the prospects of spectroscopic observation of such species. It appears that the terminal Fe═O bond is the longest in the oxo complex of 2, due to the strong trans-effect of the nitrido ligand. The corresponding LUMO of the µ-nitrido diiron oxo complex has the lowest energy among the three oxo complexes. Therefore, the oxo complex of 2 is expected to have the highest oxidative power.

Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite effective low-density lipoprotein cholesterol-targeted therapies. This review explores the crucial role of inflammation in the residual risk of ASCVD, emphasizing its impact on atherosclerosis progression and plaque stability. Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD.