Although patients with diabetes have 2 to 4 times increased risk of cardiovascular morbidity and mortality than individuals without diabetes, recent studies indicate that a significant part of ...patients are in a lower cardiovascular risk category. Men younger than 35 years, women younger than 45 years, patients with diabetes duration of less than 10 years without other risk factors have a much lower risk than patients who have traditional cardiovascular risk factors, and subclinical or established coronary artery disease (CAD). These patients are not risk equivalent as stated in previous studies. On the contrary, when in the presence of traditional risk factors or evidence of subclinical coronary disease (e.g. high coronary calcium score), the coronary risk is much increased and patients may be classified at a higher-risk category. Recent guidelines do not anymore consider diabetes as a CAD risk equivalent and recommend cardiovascular risk stratification for primary prevention. Stratification of diabetic patients improves accuracy in prediction of subclinical CAD, silent ischemia and future cardiovascular events. Stratification also discriminates higher from lower risk patients who may need intensive statin or aspirin prevention, while avoiding overtreatment in lower risk cases. It may also allow the clinician to decide whether to intensify risk reduction actions through specific newer drugs for glucose control such as SGLT-2 inhibitors or GLP-1 agonists, which recently have shown additional cardiovascular protector effect. This review addresses the assessment of cardiovascular disease risk using traditional and non-traditional cardiovascular risk factors. It also reviews the use of risk calculators and new reclassification tools, focusing on the detection of subclinical atherosclerosis as well as silent ischemia in the asymptomatic patients with diabetes.
Dyslipidemia: A Narrative Review on Pharmacotherapy de Oliveira, Lucas Lentini Herling; de Assis, Arthur Cicupira Rodrigues; Giraldez, Viviane Zorzanelli Rocha ...
Pharmaceuticals (Basel, Switzerland),
02/2024, Letnik:
17, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Dyslipidemia plays a fundamental role in the development and progression of atherosclerosis. Current guidelines for treating dyslipidemia focus on low-density lipoprotein-cholesterol (LDL-C). Despite ...advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease-statins-remain insufficient in the primary or secondary prevention of acute myocardial infarction. Advancing therapy for hypercholesterolemia with emerging new drugs, either as monotherapy or in combination, is expected to improve cardiovascular outcomes. An emerging field in dyslipidemia pharmacotherapy is research on genetic therapies and genetic modulation. Understanding the genetic mechanisms underlying lipid alterations may lead to the development of personalized treatments that directly target the genetic causes of dyslipidemia. RNA messenger (mRNA)-based therapies are also being explored, offering the ability to modulate gene expression to normalize lipid levels. Furthermore, nanotechnology raises new possibilities in drug delivery for treating dyslipidemia. Controlled-release systems, nanoparticles, and liposomes can enhance the effectiveness and safety of medications by providing more precise and sustained release. This narrative review summarizes current and emerging therapies for the management of patients with dyslipidemia.
Inflammatory Concepts of Obesity Rocha, Viviane Zorzanelli; Folco, Eduardo J.
International journal of inflammation,
01/2011, Letnik:
2011
Journal Article
Recenzirano
Odprti dostop
Obesity, long considered a condition characterized by the deposition of inert fat, is now recognized as a chronic and systemic inflammatory disease, where adipose tissue plays a crucial endocrine ...role through the production of numerous bioactive molecules, collectively known as adipokines. These molecules regulate carbohydrate and lipid metabolism, immune function and blood coagulability, and may serve as blood markers of cardiometabolic risk. Local inflammatory loops operate in adipose tissue as a consequence of nutrient overload, and crosstalk among its cellular constituents-adipocytes, endothelial and immune cells-results in the elaboration of inflammatory mediators. These mediators promote important systemic effects that can result in insulin resistance, dysmetabolism and cardiovascular disease. The understanding that inflammation plays a critical role in the pathogenesis of obesity-derived disorders has led to therapeutic approaches that target different points of the inflammatory network induced by obesity.
Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the ...adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher numbers of both CD4 and CD8 T cells than lean controls, monitored by flow cytometry. When stimulated in vitro, T cells from obese AT produced more interferon (IFN)γ than those from controls. AT from obese animals also had more cells expressing I-A, a mouse class II histocompatibility marker implicated in antigen presentation, as determined by immunostaining. Differentiated 3T3-L1 cells stimulated with recombinant IFNγ or T-helper 1–derived supernatant produced several chemokines and their mRNAs. Obese IFNγ-deficient animals had significantly reduced AT expression of mRNA-encoding inflammatory genes such as tumor necrosis factor-α and monocyte chemoattractant protein-1, decreased AT inflammatory cell accumulation, and better glucose tolerance than control animals consuming the same diet. Obese mice doubly deficient for IFNγ receptor and apolipoprotein (Apo)E on a mixed 129SvEv/C57BL/6 (129/B6) genetic background, despite exhibiting similar AT mRNA levels of tumor necrosis factor-α and monocyte chemoattractant protein-1 as 129/B6-ApoE controls, had decreased expression of important T cell–related genes, such as IFNγ-inducible protein-10 and I-A, and lower plasma triglycerides and glucose. These results indicate a role for T cells and IFNγ, a prototypical T-helper 1 cytokine, in regulation of the inflammatory response that accompanies obesity.
Update on Sitosterolemia and Atherosclerosis Rocha, Viviane Zorzanelli; Tada, Mauricio Teruo; Chacra, Ana Paula Marte ...
Current atherosclerosis reports,
05/2023, Letnik:
25, Številka:
5
Journal Article
Recenzirano
Purpose of Review
The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma ...plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either
ABCG5
or
ABCG8
, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease.
Recent Findings
Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in
ABCG5
and
ABCG8
in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in
ABCG5/ABCG8
can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia.
Summary
Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.
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