Circulating Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and Arterial Stiffness in a Large Population Sample: Data From the Brisighella Heart Study

Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulating levels are significantly associated with an increased risk of cardiovascular events. This study aimed to evaluate the relationship between circulating levels of PCSK9 and arterial stiffness, an early instrumental biomarker of cardiovascular disease risk, in a large sample of overall healthy participants

Nutraceuticals and Hypertensive Disorders in Pregnancy: The Available Clinical Evidence

The aim of the present critical review is to summarize the available clinical evidence supporting the use of some dietary supplements that have been shown to lower blood pressure in hypertensive pregnant women. A systematic search strategy was carried out to identify trials in MEDLINE (National Library of Medicine, Bethesda, Maryland, MD, USA; January 1980 to September 2019) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). The terms \u2018nutraceuticals\u2019, \u2018dietary supplements\u2019, \u2018pregnancy\u2019, \u2018pre-eclampsia\u2019, \u2018clinical trial\u2019, and \u2018human\u2019 were incorporated into an electronic search strategy. The references of the identified studies and review articles were reviewed to look for additional studies of interest. We preferably selected papers that reported recent comprehensive reviews or meta-analysis, or original clinical trials of substances with blood pressure-lowering or vascular protective effect in pregnancy. There is a relative body of evidence that supports the use of calcium, vitamin D, folic acid, and resveratrol in preventing the development of hypertensive disorders in pregnancy, and evidence supporting drug treatment too. Further clinical research is advisable to identify the dosage and timing of the supplementation, the group of women that might benefit the most from this approach, and the nutraceuticals with the best cost-effectiveness and risk-benefit ratio for widespread use in clinical practice

PCSK9 induces a pro-inflammatory response in macrophages

Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250\u2009\uf7\u20092.5\u2009\ub5g/ml) of human recombinant PCSK9 (hPCSK9). After 24\u2009h incubation with 2.5\u2009\ub5g/ml PCSK9, a significant induction of IL-1\u3b2, IL-6, TNF-\u3b1, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-\u3b1 (2.4\u2009\ub1\u20090.5 fold) and IL-1\u3b2 (8.6\u2009\ub1\u20091.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-\u3b1 mRNA in murine LDLR-/- bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3\u2009\ub1\u20091.6 fold vs 31.1\u2009\ub1\u20096.1 fold for LDLR-/- and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-\u3b1 plasma levels of healthy adult subjects (males 533, females 537) was observed (B\u2009=\u20098.73, 95%CI 7.54\u2009\uf7\u20099.93, p\u2009<\u20090.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR

Management of pregnancy-related hypertensive disorders in patients infected with SARS CoV-2: pharmacological and clinical issues

Aims: Coronavirus-19 infection (COVID-19) continues to spread throughout the world. It is known that among patients with hypertension, diabetes, chronic respiratory disease, or cardiovascular (CV) diseases, COVID-19 is associated with greater morbidity and mortality compared to patients without these conditions. This correlation is of great importance in pregnant women affected by COVID-19 since it usually leads to the development of a serious clinical complication. In particular, managing hypertensive disorders in pregnancy can be problematic because anti-hypertensive medications may interact pharmacologically with drugs used to treat COVID-19. This review focuses on the safety of drug treatment for COVID-19 in pregnant women treated with anti-hypertensive medication. Methods and results: Several databases were searched to identify relevant literature. A few anti-hypertensive drugs and antithrombotic treatments are known for having a beneficial effect in the management of hypertension and hypertensive disorders in pregnancy. In this review, we focus on the expected drug-drug interactions with the experimental agents mostly used to treat COVID-19. Conclusions: The current indication for the management of hypertension-related disorders in pregnancy maintain their validity, while the risk of pharmacological interaction with the currently tested anti-SARS-CoV-2 medications is relatively low

Vitamin D Supplementation and COVID-19 Outcomes: Mounting Evidence and Fewer Doubts

The coronavirus disease 2019 (COVID-19) has already killed more than 6 million people around the world. A growing body of epidemiological evidence suggests that low 25-hydroxy vitamin D (25-OH-vitamin D) plasma levels are associated with an increased risk of developing COVID-19 and -most importantly-with a higher risk of developing more severe COVID-19 and dying. On the other hand, vitamin D supplementation during the early phases of COVID-19 has been related to a decreased length of hospital stay, less frequent need for oxygen, and a reduced mortality rate in inpatients. This seems to be particularly true when high dosages are used. In light of this evidence, further studies are needed to define the best timing for vitamin D supplementation and the most effective dosage schedule

An Evolving Definition of a “Healthy Diet”

Throughout life, most of us eat at least three meals a day for 365 days a year. It follows that, in a 90-year life, everyone is potentially exposed to food constituents (i.e., nutrients, bioactives, and other chemical compounds) more than 95 thousand times; therefore, dietary habits are a relevant determinant of health status. In daily clinical practice, we usually discourage patients from eating foods deemed unhealthy, such as highly processed items. Even more rarely do we recommend that patients consume healthy foods, except as an alternative to junk foods. Nevertheless, it is well known that a healthy diet prevents several chronic and degenerative diseases and is the key to a healthy and long life. However, what is a healthy diet and how do we define it? Recently, a large number of epidemiological studies have attempted to identify which dietary factors correlate with negative health outcomes, including death, loss of function, and lack of well-being. Determinants of positive health outcomes have been more rarely investigated, on the contrary

Functional Foods and Nutraceuticals to Reduce the Risk of Cardiometabolic Disease: Where We Are, and Where We Are Going

Atherosclerotic cardiovascular diseases (ASCVDs) remain leading causes of mortality and disability in Western countries [...]

Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update

This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that further well-designed clinical research is needed to deepen their efficacy and safety profile

Short-term evolocumab-induced tendon xanthomas regression in an elderly patient with homozygous familial hypercholesterolemia

Homozygous Familial Hypercholesterolemia (HoFH) is a rare inherited disorder affecting 1 in 160,000 to 1 in 300,000 individuals and resulting in extremely elevated low-densitym lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). Manifestations of ASCVD most notably include fatal and non-fatal myocardial infarction (MI) and occlusive vascular disease requiring surgical or percutaneous revascularization. Deposits of cholesterol in the skin or tendons, or both, called xanthomas, are the hallmark of the disease

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic cardiovascular disease (ASCVD). Red yeast rice (RYR) is a nutraceutical widely used as a lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which is structurally identical to lovastatin and targets the same key enzyme of cholesterol biosynthesis. RYR supplementation reduces LDL-C levels by approximately 15-34% versus placebo, with a similar effect to low-dose, first-generation statins in subjects with mild-to-moderate dyslipidemia. RYR has also demonstrated beneficial reductions of up to 45% versus placebo in the risk of ASCVD events in secondary prevention studies. RYR at a dose that provides about 3 mg/d of monacolin K is well tolerated, with an adverse event profile similar to that of low-dose statins. RYR is therefore a treatment option for lowering LDL-C levels and ASCVD risk for people with mild-to-moderate hypercholesterolemia who are ineligible for statin therapy, particularly those who are unable to implement lifestyle modifications, and also for people who are eligible for statin therapy but who are unwilling to take a pharmacologic therapy