The liver and heart are closely interconnected organs, and their bidirectional interaction plays a central role in cardiometabolic disease. In this review, we summarize current evidence linking liver dysfunction—particularly metabolic dysfunction–associated steatotic liver disease, alcohol-associated liver disease, and cirrhosis—with an increased risk of heart failure and other cardiovascular diseases. We discuss how these liver conditions contribute to cardiac remodeling, systemic inflammation, and hemodynamic stress and how cardiac dysfunction in turn impairs liver perfusion and promotes hepatic injury. Particular attention is given to the molecular mediators of liver-heart communication, including hepatokines and cardiokines, as well as the emerging role of advanced research methodologies, including omics integration, proximity labeling, and organ-on-chip platforms, that are redefining our understanding of interorgan cross talk. By integrating mechanistic insights with translational tools, this review aims to support the development of multiorgan therapeutic strategies for cardiometabolic disease.

The metabolic effects of insulin predominate in skeletal muscle, fat, and liver where the hormone binds to its receptor, thereby priming a series of cell-specific and biochemically diverse intracellular mechanisms. In the presence of a good secretory reserve in the pancreatic islets, a decrease in insulin sensitivity in the metabolic target tissues leads to compensatory hyperinsulinemia. A large body of evidence obtained in clinical and experimental studies indicates that insulin resistance and the related hyperinsulinemia are causally involved in some forms of arterial hypertension. Much of this involvement can be ascribed to the impact of insulin on renal sodium transport, although additional mechanisms might be involved. Solid evidence indicates that insulin causes sodium and water retention, and both endogenous and exogenous hyperinsulinemia have been correlated to increased blood pressure. Although important information was gathered on the cellular mechanisms that are triggered by insulin in metabolic tissues and on their abnormalities, knowledge of the insulin-related mechanisms possibly involved in blood pressure regulation is limited. In this review, we summarize the current understanding of the cellular mechanisms that are involved in the pro-hypertensive actions of insulin, focusing on the contribution of insulin to the renal regulation of sodium balance and body fluids.

Alcoholic beverages are common components of diets worldwide and understanding their effects on humans’ health is crucial. Because hypertension is the leading risk factor for cardiovascular diseases and all-cause mortality, the relationship of alcohol consumption with blood pressure (BP) has been the subject of extensive investigation. For the purpose of this review, we searched the terms “alcohol”, “ethanol”, and “arterial hypertension” on Pubmed MeSH and selected the most relevant studies. Short-term studies showed a biphasic BP response after ingestion of high doses of alcohol, and sustained alcohol consumption above 30 g/day, significantly, and dose-dependently, increased the risk for hypertension. These untoward effects of alcoholic beverages on BP can be mediated by a multiplicity of neurohormonal mechanisms. In addition to the effects on BP, excess alcohol intake might contribute to cardiac and renal hypertensive organ damage, although some studies suggest possible benefits of moderate alcohol consumption on additional cardiovascular risk factors, such as diabetes and lipoprotein(a). Some intervention studies and cumulative analyses support the evidence of a benefit of the reduction/withdrawal of alcohol consumption on BP and cardiovascular outcomes. This is why guidelines of scientific societies recommend avoidance or limitation of alcohol intake below one unit/day for women and two units/day for men. This narrative article overviews all these topics, providing an update of the current knowledge on the relationship between alcohol and BP.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), including alpha-linolenic acid (ALA) and its derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are “essential” fatty acids mainly obtained from diet sources comprising plant oils, marine blue fish, and commercially available fish oil supplements. Many epidemiological and retrospective studies suggested that ω-3 PUFA consumption decreases the risk of cardiovascular disease, but results of early intervention trials have not consistently confirmed this effect. In recent years, some large-scale randomized controlled trials have shed new light on the potential role of ω-3 PUFAs, particularly high-dose EPA-only formulations, in cardiovascular prevention, making them an attractive tool for the treatment of “residual” cardiovascular risk. ω-3 PUFAs' beneficial effects on cardiovascular outcomes go far beyond the reduction in triglyceride levels and are thought to be mediated by their broadly documented “pleiotropic” actions, most of which are directed to vascular protection. A considerable number of clinical studies and meta-analyses suggest the beneficial effects of ω-3 PUFAs in the regulation of blood pressure in hypertensive and normotensive subjects. These effects occur mostly through regulation of the vascular tone that could be mediated by both endothelium-dependent and independent mechanisms. In this narrative review, we summarize the results of both experimental and clinical studies that evaluated the effect of ω-3 PUFAs on blood pressure, highlighting the mechanisms of their action on the vascular system and their possible impact on hypertension, hypertension-related vascular damage, and, ultimately, cardiovascular outcomes.

Elevated plasma lipoprotein(a) [Lp(a)] is a relatively common and highly heritable trait conferring individuals time-dependent risk of developing atherosclerotic cardiovascular disease (CVD). Following its first description, Lp(a) triggered enormous scientific interest in the late 1980s, subsequently dampened in the mid-1990s by controversial findings of some prospective studies. It was only in the last decade that a large body of evidence has provided strong arguments for a causal and independent association between elevated Lp(a) levels and CVD, causing renewed interest in this lipoprotein as an emerging risk factor with a likely contribution to cardiovascular residual risk. Accordingly, the 2022 consensus statement of the European Atherosclerosis Society has suggested inclusion of Lp(a) measurement in global risk estimation. The development of highly effective Lp(a)-lowering drugs (e.g., antisense oligonucleotides and small interfering RNA, both blocking LPA gene expression) which are still under assessment in phase 3 trials, will provide a unique opportunity to reduce “residual cardiovascular risk” in high-risk populations, including patients with arterial hypertension. The current evidence in support of a specific role of Lp(a) in hypertension is somehow controversial and this narrative review aims to overview the general mechanisms relating Lp(a) to blood pressure regulation and hypertension-related cardiovascular and renal damage.