There are those who would like zero LDL cholesterol.

The overwhelming evidence that the reduction of LDL cholesterol (LDLc) levels is associated with a parallel reduction in cardiovascular (CV) risk has led the scientific community to progressively and constantly reduce the optimal therapeutic targets of LDLc, both in patients with known CV disease and in patients undergoing primary prevention. The recent introduction of proprotein convertase subtilisin/kexin type 9 inhibitors has allowed clinicians to observe reductions in LDLc levels that go well beyond the limits set by the main international guidelines; following the 'the lower the better' paradigm, it is natural to ask how low LDLc can be reduced, whether this intervention is associated with a further reduction in CV risk and, above all, whether there are no issues related to safety in the use of polypharmacotherapies that determine an extreme reduction in LDLc levels. The purpose of this article is to summarize the main scientific evidence on the topic, trying to provide an answer to all clinicians who 'would like their LDLc to be-almost-zero'.

Clinical results and mechanism of action of icosapent ethyl.

Serum triglyceride concentration is considered as an additional component that often contributes to residual cardiovascular risk in patients already at high risk; these considerations have led to several clinical studies aimed at evaluating the efficacy of supplements based on omega-3 fatty acids in reducing serum triglyceride levels and consequently cardiovascular risk. Although partially inconclusive and contradictory, these clinical trials laid the foundations for the implementation of the REDUCE-IT and EVAPORATE studies, in which the use of a purified derivative of eicosapentaenoic acid, icosapent ethyl, resulted in a significant reduction both of the composite for cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke and of the reduction in the volumetric progression up to the induction of a real regression of the coronary atheromatous plaques detected by computerized coronary angiography tomography. Surprisingly, these brilliant results seem to be, at least in part, not related to the reduction of triglyceride concentration. The purpose of this article is to examine the latest evidence regarding icosapent ethyl therapy, describing the results of the main clinical trials performed to date and formulating hypotheses on the potential mechanisms of action of this fascinating molecule.

'Use of lipid-lowering therapy: the guidelines, the drugs or the patient?'

The current step up approach in the therapy of dyslipidemias aims to reduce the amount of LDL cholesterol below a threshold that varies according to the patient's risk category, with a pharmacological approach that sees statins as a fundamental cornerstone. Although absolutely functional in reducing cardiovascular events, this therapeutic algorithm does not yet take into consideration the innumerable phenotypic variables that we can find in dyslipidemic subjects. The ever finer understanding of the pathophysiological mechanisms underlying dyslipidemias in combination with the novelties obtained through DNA genotyping will allow, in the near future, the development of a 'tailor-made' therapy for each category of patients. This article will summarize the most recent evidence regarding the therapy of dyslipidemias, with particular attention to the concept of cumulative exposure and some hypotheses on possible initial therapeutic proposals in patients with diabetes, vasculopathy, with hypertriglyceridaemia and with high levels of Lp (a).

[New evidence on coffee consumption, hypertension and cardiovascular diseases]. / Caffè, ipertensione e malattie cardiovascolari: nuove acquisizioni.

Coffee is the most widespread drink in the world, immediately after water. In the United States, coffee consumption amounts to 400 million cups per day and is, globally, the main source of caffeine. In view of such a high worldwide use, it is of great interest for the scientific community to understand whether or not this drink has an impact on health. In the first clinical studies aimed at investigating the effects of coffee, a possible deleterious effect on systemic blood pressure and on the incidence of cardiovascular diseases was hypothesized. These data have been interpreted on the basis of the mild increase in blood pressure that can occur immediately following the consumption of caffeine. Coffee, however, contains more than 1000 chemical components, among which are polyphenols such as chlorogenic acid and lignans, with antioxidant and anti-inflammatory properties, and substances with a vasodilating action such as vitamin E, niacin, potassium and magnesium. It is therefore likely that if, on the one hand, caffeine causes a mild increase in blood pressure, on the other hand, the countless substances contained in coffee are able to counteract this effect, actually resulting in a health benefit. The latest evidence available in the literature shows indeed how the consumption of 3-5 cups of coffee a day is not only harmless, but is even able to significantly reduce the incidence of and mortality from cardiovascular diseases, as well as mortality from all causes.

Surprises in cardiology: efficacy of gliflozines in heart failure even in the absence of diabetes.

It is now well-established that the therapy of type II diabetes mellitus has undergone a radical change in the past 15 years: countless innovative drugs, such as SGLT2I, able to guarantee an optimization of glycaemic control without causing hypoglycaemia, today represent real therapeutic cornerstones not only for the intrinsic ability of these molecules to ensure better glycaemic control but also for the effects they exert on the cardiovascular system. Several pioneering clinical trials, such as EMPA-REG, CANVAS, and DECLARE-TIMI-58, have demonstrated clear benefits of empagliflozin, canagliflozin, and dapagliflozin, respectively, in reducing cardiovascular risk and diabetes-associated macrovascular complications in the diabetic population. The promising results that emerged from these trials represent the spark that triggered a series of studies aimed at evaluating the efficacy of gliflozines in the treatment of patients with heart failure even in the absence of diabetes. Preliminary results confirm the efficacy of SGLT2I in the treatment of this population, representing a real therapeutic revolution.

The new type 2 diabetes mellitus therapy: comparison between the two classes of drugs GLPR (glucagon-like peptide receptor) agonists and SGLT2 (sodium-glucose cotransporter 2) inhibitors.

Type 2 diabetes mellitus represents one of the most common chronic-degenerative diseases in modern society and is the cause of innumerable micro- and macrovascular complications that weigh on the national health system. Until a few years ago, there was no anti-diabetic drug that, in addition to lowering blood sugar, had an impact on cardiovascular risk in these patients. In this report, we will analyse the characteristics, contraindications, and evidence in favour of the use of two innovative categories of molecules that aim, for the first time in history, at controlling blood sugar levels and simultaneously lower cardiovascular risk in diabetics individuals: the glucagon-like peptide receptor agonists and the sodium-glucose cotransporter 2 inhibitors.

Safety implications of combining ACE inhibitors with thiazides for the treatment of hypertensive patients.

INTRODUCTION: ACE-inhibitors (ACEI) and diuretics are the typical first-line antihypertensive drugs with complementary mechanisms of action. The present paper is summarizing the evidence supporting the efficacy of their combination in a broad range of hypertensive patients. AREAS COVERED: This source of data is different trials investigating the use of ACEI and diuretics in different populations of patients. The available evidence supports some advantage for thiazide-type compounds (chlortalidone-CHT and indapamide-IND) in the prevention of major CV complications. In terms of safety, hydrochlorothiazide (HCTZ) and indapamide are associated with a lesser rate of hypokalemia and abnormalities of metabolic profile (glucose control, uric acid levels, serum potassium levels). As far as the results of clinical trials, the most relevant studies are involving the combination of benazepril or perindopril with HCTZ (benazepril) or IND (Perindopril) respectively. All these studies have resulted in a favorable clinical outcome. In terms of safety profile, the combination of ACEi and diuretic is safe and comparable with that of ACEi and calcium channel blockers with no differences in the rate of major adverse events (cough or angioedema) and a lower rate of ankle edema. EXPERT OPINION: The combination of ACEi and diuretic is safe and well-tolerated and should be considered among the first-line treatments in most of the patients with hypertension.