Frontiers of cardiovascular polypills: From atherosclerosis and beyond.

Fixed-dose combination (FDC) therapies (also known as polypills) remain underutilized in clinical practice despite over two decades of evidence from randomized controlled trials demonstrating increased adherence to multidrug therapy, improved cardiovascular disease (CVD) risk factor control, and lower incidence of cardiovascular events. Evidence demonstrates that FDC-based implementation strategies can substantially complement and augment current strategies for CVD risk prevention globally. The next decade is likely to extend the frontier of cardiovascular FDC therapies, particularly given expected advances in FDC manufacturing technology and accessibility. FDC-based anti-hypertensive therapies are emerging as integral components of a pragmatic blood pressure lowering strategy. Cardiovascular FDCs are rapidly approaching its coming of age, transforming from heavily hyped research tools to pragmatic clinical instruments. This review evaluates the current evidence for cardiovascular FDCs, barriers to current use, and potential next generation advances.

Subclinical atherosclerosis and cardiovascular markers in patients with lichen planus: A case-control study.

BACKGROUND: Lichen planus is an idiopathic and chronic inflammatory disease that affects the skin and the mucous membranes, and has been associated with an increased risk for cardiovascular diseases. Hyperhomocysteinemia has been regarded as a risk factor for atherosclerosis and cardiovascular diseases. Increased plasma fibrinogen levels are also associated with increased risk of myocardial infarction. OBJECTIVE: The main aim of this study is the evaluation of common carotid artery mean intima media wall thickness, serum fibrinogen and homocysteine levels in patients with lichen planus. METHODS: Forty-three patients with lichen planus and 43 age, gender and body mass index (BMI) matched healthy controls (from general population without the disease) were included in this study. RESULTS: Compared to the healthy controls, patients had statistically significant greater mean intima media wall thickness of the common carotid artery. Moreover, a positive correlation was observed between lichen planus and increased serum homocysteine and c-reactive protein levels. LIMITATIONS: The main limitation of this study is the small sample size due to the time limitation and financial constraints. CONCLUSION: Early diagnosis of atherosclerosis in patients with lichen planus might afford better prophylaxis, including weight control and/or lipid profile monitoring. Measurement of the mean intima media wall thickness of the common carotid artery by duplex high-resolution B-mode ultrasound scanning could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus.

Comprehensive lipid tetrad index, atherogenic index and lipid peroxidation: Surrogate markers for increased cardiovascular risk in psoriasis.

BACKGROUND AND OBJECTIVES: Recently, the concept of "psoriatic march" has come to the fore, in which chronic cutaneous inflammation in psoriasis leads to systemic inflammation which, in conjunction with increased oxidative stress, triggers a cascade of events resulting in increased cardiovascular risk in patients with severe psoriasis. We, therefore, decided to study the levels of some biochemical cardiovascular risk markers: lipid peroxidation (malondialdehyde), lipoprotein (a), lipid indices and atherogenic index, in patients with psoriasis and their association with disease severity. METHODS: Forty five patients with psoriasis and 45 age and gender-matched healthy controls were included in this cross-sectional study. Disease severity was assessed by the Psoriasis Area Severity Index (PASI). Serum malondialdehyde, lipoprotein (a) and fasting lipid profile were estimated in all study subjects. Lipoprotein ratios were computed using standard formulae. Atherogenic index was calculated as ratio of lipoprotein (a)/high-density lipoprotein. RESULTS: In psoriasis, we observed significantly higher levels of malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, lipoprotein (a), lipid ratios, atherogenic index and comprehensive lipid tetrad index, compared to controls. These levels were directly proportional to disease severity. Serum levels of malondialdehyde correlated positively with serum lipoprotein (a), comprehensive lipid tetrad index and atherogenic index. LIMITATIONS: Different morphological types of psoriasis were not included and follow-up post-therapy was not done. A larger sample size would have validated the results further. CONCLUSION: Our results indicate that psoriasis, especially the severe variants, are associated with increased oxidative stress and dyslipidemia, which correlate positively with atherogenic index and hence, an increased cardiovascular risk.

TECA (Titrated Extract of Centella Asiatica): new microcirculatory, biomolecular, and vascular application in preventive and clinical medicine. A status paper.

Plant-derived elements used for pharmacological applications constitute an increasing research field. Centella asiatica is widely used mainly as an extract (TECA). Triterpenic fractions, the primary constituents of Centella asiatica, produce a wide range of preventive and therapeutic effects. The modulation of collagen production and deposition in wound healing is of primary importance. TECA is also used to treat several microcirculatory problems, inflammatory skin conditions (leprosy, lupus, varicose ulcers, eczema, atopic dermatitis, psoriasis) and also intestinal problems, fever, amenorrhea and genitourinary conditions. Cognitive functions, anxiety and mental impairment may be also affected by TECA administration. New applications in neurology include nerve growth factor enhancement and applications in neurological degenerative conditions. Interaction with other products is also indicated in this document. The multiplicity of actions of TECA is associated to six important mechanisms, all inter-connected and modulating each other: 1) edema - and capillary filtration - control; 2) a strong antioxidant power, effective on several forms of oxidative stress associated to inflammation or infections and synergic with other antioxidant products; 3) an anti-inflammatory action; 4) a modulation of the collagen production avoiding slower scarring or faster, hyperthrophic scarring and cheloids; 5) a modulating action of local growth factors; 6) a modulation of angiogenesis. This "status" paper - resulting from an expert meeting held in Cobham, Surrey, indicates most of the therapeutic potential of TECA, still to be explored in further studies. The status paper constitutes the basis for a consensus document on TECA to be developed in the next future. This "status" paper opens a new window on an ancient but still partially unexplored product that may become an important value in prevention and treatment of several pre-clinical and risk conditions and in clinically significant disease both as a single products and in association with other 'natural' products.

Th1 polarized response induced by intramuscular DNA-HSP65 immunization is preserved in experimental atherosclerosis

We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardiovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 mug DNA-HSP65. On day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.

Th1 polarized response induced by intramuscular DNA-HSP65 immunization is preserved in experimental atherosclerosis.

We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardiovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 microg DNA-HSP65. On day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.

Avaliaçäo dos níveis de lipídios, lipoproteínas, apoproteínas e o papel da lipoproteína(a) na desenvolvimento de aterosclerose e alterações fibrinolíticas nos pacientes portadores de hanseníase virchoviana / Avaliation of lipidis levels, lipoproteins, apoproteins and lixoproteins paper at atherosclerosis development and altering fibrinolitics

Muitos portadores de hanseníase virchoviana, após longo tempo de evoluçäo, apresentam alterações dérmicas muito semelhantes aos xantonas e seus exames histológicos mostram numerosos macrófagos carregados de material lipídico. Esses fatos, associados a alteraçöes humorais dos lipídios descritas na literatura, sugerindo alteraçöes no metabolismo dos mesmos, levou-nos a estudos, visando a estabelecer valores médios em pacientes, utilizando-se de novas determinaçöes lipoprotêicas e de apoproteínas muito mais precisas. A lipoproteína(a) apresentou valor médio acima de 20 mg/dl em 64,6(por cento) dos pacientes, contra 33,3(por cento) no grupo controle. O encontro de lipoproteína(a) aumentada em pacientes portadores de hanseníase virchoviana é importante, porque existe uma comprovada relaçäo entre esta lipoproteína e alteraçöes vasculares tipo ateroscleróticas e distúrbios na fibrinólise