scholarly journals Hydrophilic or Lipophilic Statins?

2021 ◽  
Vol 8 ◽  
Author(s):  
Elisenda Climent ◽  
David Benaiges ◽  
Juan Pedro-Botet
Keyword(s):  
Clinical Evidence ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Prevention ◽  
Cardiovascular Outcomes ◽  
The Other ◽  
Solubility Profile ◽  
Other Regarding ◽  
Secondary Cardiovascular Prevention

Drugs can be classified as hydrophilic or lipophilic depending on their ability to dissolve in water or in lipid-containing media. The predominantly lipophilic statins (simvastatin, fluvastatin, pitavastatin, lovastatin and atorvastatin) can easily enter cells, whereas hydrophilic statins (rosuvastatin and pravastatin) present greater hepatoselectivity. Although the beneficial role of statins in primary and secondary cardiovascular prevention has been unequivocally confirmed, the possible superiority of one statin or other regarding their solubility profile is still not well-established. In this respect, although some previously published observational studies and clinical trials observed a superiority of lipophilic statins in cardiovascular outcomes, these results could also be explained by a greater low-density lipoprotein cholesterol reduction with this statin type. On the other hand, previous studies reported conflicting results as to the possible superiority of one statin type over the other regarding heart failure outcomes. Furthermore, adverse events with statin therapy may also be related to their solubility profile. Thus, the aim of the present review was to collect clinical evidence on possible differences in cardiovascular outcomes among statins when their solubility profile is considered, and how this may also be related to the occurrence of statin-related adverse effects.

LDL-cholesterol lowering efficacy of atorvastatin® in primary prevention. Real-world experience in a developing country; a program based on evidence, personalization, and empowerment

2021 ◽  
Vol 9 (11) ◽  
Author(s):  
Enrique Morales-Villegas ◽  
Abigail Vega-Velasco ◽  
Gualberto Moreno-Virgen
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Prevention ◽  
Scientific Quality ◽  
Atherosclerotic Cardiovascular Disease ◽  
Net Benefit ◽  
Therapeutic Class ◽  
Risk Patients

Despite the iconoclasts of the LDL-centric principle and the net benefit of statins, the plurality, quantity, and especially the scientific quality of the evidence that supports the causal role of low-density lipoprotein cholesterol (LDL-C) in atherosclerosis, as well as the net benefit of statins in its prevention, make these two concepts, universal principles accepted by all guidelines worldwide. The efficacy, safety, and cost-effectiveness of statins have been confirmed in multiple randomized and controlled clinical trials. However, paradoxically, and especially in developing countries like Mexico, the use of this therapeutic class is suboptimal. The reasons to explain this paradox are multiple and are analyzed in this article, which has the purpose of confirming the efficacy, safety, and significant potential impact of statins in the "real developing world." To fulfill this purpose, this article presents our center experience using statins, especially atorvastatin®, in patients without atherosclerotic cardiovascular disease (ASCVD). Founded on an evidence-based, personalization, and empowerment program, our results in almost four hundred patients in primary cardiovascular prevention are as follows. In intermediate-risk patients, atorvastatin® 10 mg/day with a baseline LDL-C of 111.6 mg/dL (±25.1), reduced LDL-C by 38.0% (±13.9); atorvastatin® 20 mg/day with a baseline LDL-C of 124.4 mg/dL (±25.3), reduced LDL-C by 44.9% (±15.0) (p <0.005 for both). In the atorvastatin® 10/20 mg/day cohort (a total of 294 patients), 87.7% (258 patients) achieved a ≥30% LDL-C reduction, and 36.7% (108 patients) a ≥50% reduction. In the atorvastatin 10/20 mg/day cohort, with an average baseline LDL-C of 122.6 mg/dL (±25.6), 92.5 and 55.7% achieved LDL-C of ≤100 and ≤70 mg/dL, respectively. In high-risk patients, atorvastatin® 40 mg/day with a baseline LDL-C of 151.7 mg/dL (±31.6), there was an LDL-C average reduction of 54.7% (±12.2). Atorvastatin 80mg/day with a baseline LDL-C of 160.2 mg/dL (±41.5) produced an LDL-C average reduction of 62.5% (±10.8) (P <0.005 for both). In the atorvastatin® 40/80 mg/day cohort (89 patients), 98.8% (88 patients) achieved a ≥30% LDL-C reduction, and 76.4% (68 patients) achieved a ≥50% reduction. In the atorvastatin 40/80 mg/day cohort, with an average baseline LDL-C of 153.0 mg/dL (±33.2), 95.8 and 62.9% achieved LDL-C of ≤100 and ≤70 mg/dL, respectively.

The Role of the Low-Density Lipoprotein Receptor-Related Protein (LRP) in the Plasma Clearance and Liver Uptake of Recombinant Single-chain Urokinase-type Plasminogen Activator in Rats

1997 ◽  
Vol 77 (04) ◽  
pp. 710-717 ◽  
Author(s):  
Marieke E van der Kaaden ◽  
Dingeman C Rijken ◽  
J Kar Kruijt ◽  
Theo J C van Berkel ◽  
Johan Kuiper
Keyword(s):  
Plasminogen Activator ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Single Chain ◽  
Liver Uptake ◽  
Type Plasminogen Activator ◽  
Parenchymal Liver ◽  
Urokinase Type Plasminogen Activator ◽  
Density Lipoprotein Receptor

SummaryUrokinase-type plasminogen activator (u-PA) is used as a thrombolytic agent in the treatment of acute myocardial infarction. In vitro, recombinant single-chain u-PA (rscu-PA) expressed in E.coli is recognized by the Low-Density Lipoprotein Receptor-related Protein (LRP) on rat parenchymal liver cells. In this study we investigated the role of LRP in the liver uptake and plasma clearance of rscu-PA in rats. A preinjection of the LRP inhibitor GST-RAP reduced the maximal liver uptake of 125I-rscu-PA at 5 min after injection from 50 to 30% of the injected dose and decreased the clearance of rscu-PA from 2.37 ml/min to 1.58 ml/min. Parenchymal, Kupffer and endothelial cells were responsible for 40, 50 and 10% of the liver uptake, respectively. The reduction in liver uptake of rscu-PA by the preinjection of GST-RAP was caused by a 91 % and 62% reduction in the uptake by parenchymal and Kupffer cells, respectively. In order to investigate the part of rscu-PA that accounted for the interaction with LRP, experiments were performed with a mutant of rscu-PA lacking residues 11-135 (= deltal25- rscu-PA). Deletion of residues 11-135 resulted in a 80% reduction in liver uptake and a 2.4 times slower clearance (0.97 ml/min). The parenchymal, Kupffer and endothelial cells were responsible for respectively 60, 33 and 7% of the liver uptake of 125I-deltal25-rscu-PA. Preinjection of GST-RAP completely reduced the liver uptake of delta 125-rscu-PA and reduced its clearance to 0.79 ml/min. Treatment of isolated Kupffer cells with PI-PLC reduced the binding of rscu-PA by 40%, suggesting the involvement of the urokinase-type Plasminogen Activator Receptor (u-PAR) in the recognition of rscu-PA. Our results demonstrate that in vivo LRP is responsible for more than 90% of the parenchymal liver cell mediated uptake of rscu-PA and for 60% of the Kupffer cell interaction. It is also suggested that u-PAR is involved in the Kupffer cell recognition of rscu-PA.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

scholarly journals Psycho-Social Factors in Patients with Cardiovascular Disease Attending a Family-Centred Prevention and Rehabilitation Programme: EUROACTION Model in Spain

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 89
Author(s):  
Cristina Buigues ◽  
Ana Queralt ◽  
Jose Antonio De Velasco ◽  
Antonio Salvador-Sanz ◽  
Catriona Jennings ◽  
...  
Keyword(s):  
Social Factors ◽  
Illness Perceptions ◽  
Vegetable Consumption ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cardiovascular Prevention ◽  
Anxiety And Depression ◽  
Coronary Patients ◽  
Low Levels ◽  
One Year

Background: Coronary heart disease (CHD) persists as the leading cause of death worldwide. Cardiovascular prevention and rehabilitation (CVPR) has an interdisciplinary focus, and includes not only in physiological components, but it also addresses psycho-social factors. Methods: The study analysed the Spanish psycho-social data collected during the EUROACTION study. In Spain, two hospitals were randomised in the Valencia community. Coronary patients were prospectively and consecutively identified in both hospitals. The intervention hospital carried out a 16-week CVPR programme, which aimed to assess illness perceptions and establish healthy behaviours in patients and their partners. Results: Illness perceptions were significantly and inversely associated with anxiety and depression. Low levels of anxiety were associated with better self-management of total cholesterol (p = 0.004) and low-density lipoprotein-cholesterol (p = 0.004). There was concordance at one year among patients and partners who participated in the programme related to anxiety (p < 0.001), fruit consumption (p < 0.001), and vegetable consumption (p < 0.001). Conclusions: The EUROACTION study emphasised the importance of assessing psycho-social factors in a CVPR programme and the inclusion of family as support in patients’ changes in behaviour.

Abstract 3691: Deletion of Suppressor Of Cytokine Signaling-1 in a Murine Model of Atherosclerosis Results in a Lethal Systemic Inflammation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christina Grothusen ◽  
Harald Schuett ◽  
Stefan Lumpe ◽  
Andre Bleich ◽  
Silke Glage ◽  
...  
Keyword(s):  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
The Impact

Introduction: Atherosclerosis is a chronic inflammatory disease of the cardiovascular system which may result in myocardial infarction and sudden cardiac death. While the role of pro-inflammatory signaling pathways in atherogenesis has been well characterized, the impact of their negative regulators, e.g. suppressor of cytokine signaling (SOCS)-1 remains to be elucidated. Deficiency of SOCS-1 leads to death 3 weeks post-partum due to an overwhelming inflammation caused by an uncontrolled signalling of interferon-gamma (IFNγ). This phenotype can be rescued by generating recombination activating gene (rag)-2, SOCS-1 double knock out (KO) mice lacking mature lymphocytes, the major source of IFNγ. Since the role of SOCS-1 during atherogenesis is unknown, we investigated the impact of a systemic SOCS-1 deficiency in the low-density lipoprotein receptor (ldlr) KO model of atherosclerosis. Material and Methods: socs-1 −/− /rag-2 −/− deficient mice were crossed with ldlr-KO animals. Mice were kept under sterile conditions on a normal chow diet. For in-vitro analyses, murine socs-1 −/− macrophages were stimulated with native low density lipoprotein (nLDL) or oxidized (ox)LDL. SOCS-1 expression was determined by quantitative PCR and western blot. Foam cell formation was determined by Oil red O staining. Results: socs-1 −/− /rag-2 −/− /ldlr −/− mice were born according to mendelian law. Tripel-KO mice showed a reduced weight and size, were more sensitive to bacterial infections and died within 120 days (N=17). Histological analyses revealed a systemic, necrotic, inflammation in Tripel-KO mice. All other genotypes developed no phenotype. In-vitro observations revealed that SOCS-1 mRNA and protein is upregulated in response to stimulation with oxLDL but not with nLDL. Foam cell formation of socs-1 −/− macrophages was increased compared to controls. Conclusion: SOCS-1 seemingly controls critical steps of atherogenesis by modulating foam cell formation in response to stimulation with oxLDL. SOCS-1 deficiency in the ldlr-KO mouse leads to a lethal inflammation. These observations suggest a critical role for SOCS-1 in the regulation of early inflammatory responses in atherogenesis.

Abstract 14727: Meteorin-like Glial Cell Differentiation Regulator is a Novel Protein Biomarker of Cardiovascular Outcomes in Patients With Diabetes and Vascular Disease: A TECOS Substudy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lauren K Truby ◽  
Jessica A Regan ◽  
Maggie Nguyen ◽  
Stephani Giamberardino ◽  
Robert J Mentz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Conditional Logistic Regression ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Specific Protein ◽  
Cardiovascular Outcomes ◽  
Diabetic Patients ◽  
Proteomic Profiling ◽  
Protein Biomarkers ◽  
Novel Protein

Introduction: To date, there are limited data on the potential role of proteomic biomarkers to predict future cardiovascular (CV) events among patients with type 2 diabetes mellitus (DM). Hypothesis: Specific protein biomarkers will be predictive of major adverse CV events (MACE) and incident heart failure hospitalization (HFH) among patients with DM. Methods: Using the Olink aptamer-based platform, we performed proteomic profiling (>700 proteins) on 440 paired cases and matched controls from placebo-assigned participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Cases were defined as having met the primary composite outcome of MACE or incident HFH and matched to controls on baseline prevalent heart failure, coronary artery disease, BMI, hemoglobin A1C, creatinine, low-density lipoprotein cholesterol, fasting status and ejection fraction. Conditional logistic regression was used to determine the association between log-transformed relative protein expression and incident MACE or HFH. False-discovery-rate (FDR) was used to adjust for multiple comparisons. Results: We identified three specific proteins that were significantly associated with prevalent MACE or HFH: METRNL, Notch 3, and ROR1 (OR 2.1, 1.6, 1.7 and q-value 0.01, 0.02, and 0.05 respectively) (Figure 1). METRNL, in particular, performed similarly to the established biomarker NT-proBNP (Figure 1). When MACE and HFH were analyzed separately, METRNL, in particular, remained strongly associated with both outcomes (OR 2.0, p<0.001 and OR 2.7, p=0.05). Conclusions: Three novel protein biomarkers, in particular METRNL (a circulating adipokine that regulates insulin-sensitivity), may identify diabetic patients at high risk for subsequent HF and MACE. Additional studies are needed to replicate these findings and uncover the biologic mechanism linking adipokine signaling and heart failure.

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