Homocysteine has long been studied as a potential cardiovascular risk factor due to its biochemical role in endothelial dysfunction, oxidative stress, inflammation, and thrombogenesis. Despite strong epidemiological and mechanistic support, the translation of homocysteine-lowering interventions into clinical benefit remains controversial. This non-systematic review aims to clarify the current understanding of homocysteine in the cardiovascular setting by distinguishing between well-established facts, clinically relevant interventions, and persistent misconceptions. We first revisit the historical emergence of homocysteine as a cardiovascular biomarker and explore its pathophysiological mechanisms, including endothelial damage, atherosclerosis progression, and prothrombotic effects—supported by in vitro and animal model studies. Subsequently, we evaluate evidence-based interventions such as B-vitamin supplementation (folate, B6, B12), lifestyle modifications, and the clinical relevance of homocysteine monitoring in specific populations (e.g., MTHFR mutations, chronic kidney disease). We then discuss common pitfalls, including the overinterpretation of genetic variants, the inappropriate use of supplementation, and the overreliance on surrogate biomarkers in clinical trials. Although elevated homocysteine remains a reproducible biomarker of cardiovascular risk, current evidence does not support routine intervention in unselected populations. A precision medicine approach—targeting high-risk subgroups and integrating homocysteine into broader cardiometabolic management—may help unlock its therapeutic relevance. Future pharmacological strategies should prioritize mechanistic insight, patient stratification, and clinically meaningful endpoints.

Arterial hypertension remains the major cardiovascular risk worldwide. It is estimated that under 50 years of age one in every three adults is hypertensive while beyond the age of 50 the prevalence is almost 50% globally. The latest World Health Organization (WHO) Global Report on Hypertension indicated that the global number of hypertensive patients almost doubled in the last three decades, with related increasing deaths, disability, and costs annually. Because of this global increase, early diagnosis and timely treatment is of great importance. However, based on the WHO Global Report, it is estimated that up to 46% of individuals were never diagnosed. Of those diagnosed, less than 50% were on treatment, with nearly half among these at target according to the current guidelines. It is also important to note that an increasing number of hypertensive patients, despite the use of three or more drugs, still do not achieve a blood pressure normalization, thus defining the clinical scenario of resistant hypertension (RH). This condition is associated to a higher risk of hypertension-mediated organ damage and hospitalization due to acute cardiovascular events. Current guidelines recommend a triple combination therapy (renin angiotensin system blocking agent + a thiazide or thiazide-like diuretic + a dihydropyridinic calcium-channel blocker) to all patients with RH. Beta-blockers and mineralocorticoid receptor antagonists, alone or in combination, should be also considered based on concomitant conditions and potential contraindications. Finally, the renal denervation is also proposed in patients with preserved kidney function that remain hypertensive despite the use of maximum tolerated medical treatment. However, the failure of this procedure in the long term and the contraindication in patients with kidney failure is a strong call for a new therapeutic approach. In the present review, we will discuss the pharmacological novelties to come for the management of hypertension and RH in the next future.

The nitric oxide (NO) pathway is a fundamental regulator of vascular tone, myocardial function, and inflammation. In heart failure (HF), especially in advanced stages, dysregulation of NO–soluble guanylate cyclase (sGC)–cyclic guanosine monophosphate (cGMP) signaling contributes to endothelial dysfunction, increased vascular resistance, myocardial fibrosis, and impaired cardiac performance. Chronic inflammation further reduces NO bioavailability, exacerbating HF progression This review synthesizes current knowledge on the role of the NO pathway in HF pathophysiology, with a focus on stable and advanced HF. Special attention is given to patient subgroups with comorbidities such as chronic kidney disease, where modulation of NO signaling may be particularly beneficial. We also evaluate therapeutic strategies targeting NO bioavailability and sGC stimulation. Evidence shows that impaired NO signaling promotes systemic and pulmonary vasoconstriction, elevates ventricular afterload, and worsens cardiac remodeling. Pharmacological agents that restore NO levels or activate downstream effectors such as sGC improve vasodilation, reduce fibrosis, and enhance myocardial relaxation. These effects are especially relevant in advanced HF patients and those with renal impairment, who often exhibit limited responses to conventional therapies. The NO pathway represents a promising therapeutic target in both stable and advanced HF. Modulating this pathway could improve outcomes, particularly in complex populations with multiple comorbidities, highlighting the need for further clinical research and tailored treatments.

Sodium nitroprusside (SNP) is a powerful vasodilator approved for treating acute hypertensive crises, acute heart failure, aortic dissection, and both controlled perioperative hypotension and perioperative hypertension. Its unique ability to cause both venous and arterial dilation makes it an invaluable option in critical care settings. Despite concerns regarding its manageability due to potential toxicity, it is a safe choice if properly used, as highlighted by its short half-life and minimal side effects. This review aims to summarize its pharmacological properties, toxicology, and various clinical applications, particularly focusing on acute heart failure and hypertensive emergencies.

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and “rapid” achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of “go lower, start earlier and keep longer!” should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score.

Cardiovascular diseases remain the main cause of death and disability worldwide. Despite the tremendous improvement in pharmacological, minimally invasive and rehabilitative strategies, global deaths due to cardiovascular diseases are still increasing. Additional risk factors have been recently proposed, and thanks to scientific progress, novel drugs for the control of the main risk factors focusing on the cardiometabolic pathways have been identified. Glucagon-like peptide-1 (GLP-1) receptor agonists represent an innovative step in the management of patients affected by type 2 diabetes mellitus. In addition to their significant efficacy on glycemic homeostasis, some members of this class of drugs have indications in the treatment of obesity. Furthermore, accumulated evidence in the literature has finally suggested a protective role in cardiovascular health. The possible role of GLP-1R agonist drugs (GLP-1RAs) on the mechanisms underlying chronic inflammation and the almost ubiquitous distribution of GLP-1 receptors could explain the enormous versatility of these drugs. Semaglutide is a GLP-1RA recently proven to be effective in cardiovascular outcomes. In the present article, we will review the available data on semaglutide in light of the most recent publications to better characterize the target population achieving cardiovascular benefits.