Editorial: Endocrine insights into heart disease

Rogério Faustino Ribeiro Júnior¹Daigo SAWAKI²Li Chan³Gabor Czibik^3*

• ¹Universidade Federal do Espirito Santo, Vitoria, Brazil
• ²Jichi Medical School, Shimotsuke, Japan
• ³Queen Mary University of London, London, United Kingdom

Apart from familial cardiomyopathies evolving based on disease-causing mutations of myocardial proteins, cardiovascular diseases do not develop in isolation. Common causes of and composite eDects in cardiovascular disease tend to be more elusive. Some inducers include unhealthy diets promoting atherosclerosis or hypertension and age as well as sedentary lifestyle that are recognised determinants of cardiovascular disease. Increased incidence and prevalence of cardiovascular disease in patients with chronic liver or kidney disease underscore the importance of interdependent organorgan interactions in health and disease. Sustained overactivation of the sympathicoadrenergic or renin-angiotensin-aldosterone systems (RAAS) straining the heart or vasculature illustrate classic endocrine influences over the cardiovascular system. These examples notwithstanding, relatively little is known about how dysfunction of one organ begets dysfunction in the cardiovascular system. 1 Due to the reductionistic nature of scientific studies, there is a long way to the discovery of how seemingly disparate alterations impair cardiovascular health. This is particularly so when classic physiology does not come to the aid of our investigations.There is much to be learned about an organism composed of symbiotic cells fated to live and die together. Questions include, but are not limited to how adverse influences work? Does a singular abnormality emerge as a loss-of-function of physiological activity (e.g. loss of kidney function altering extracellular volume or ion composition) or gain-offunction to induce detrimental changes (e.g., secretion of factors promoting organ damage)? How is the damage signal conveyed: via secretion, through bodily fluids, such as blood, the neural system or some other way? Which cells are responsible, and which ones are aDected? How does the eDect manifest? Are molecular eDects mediated through receptors expressed by certain cell types or using other channels of cellular communication? Can we detect cardiovascular diseases from the blood? Are there easily measurable signs before a crippling disorder develops or is at a still reversible stage?In line with these questions (to some of which we already have answers) there is a considerable clinical interest in discovering predictors (precede the condition, signifying its coming) or markers (simultaneous with the condition, and incrementally indicates degree of severity) of cardiovascular disease. Criteria for good disease predictors and markers include that they draw attention to a specific condition to be prevented or stopped with great accuracy, i.e., with negligible chance for false negative and/or positive cases. By replacing or reducing the need for expensive equipment and/or specialised expertise, these diagnostic tools are meant to be simpler, and more cost-eDective than traditional diagnosis. Functionally a good predictor/marker may be an epiphenomenon, a change that develops contemporaneously with the condition, but with no causal eDect on the condition per se. It could be for example a product with a minor function cosecreted in stochiometric quantity with a more important factor (i.e., C-peptide cosecreted with insulin). The other kind of predictor/marker is intricately involved in the pathogenesis of the condition (such as insulin in glucose homeostasis and anabolism), without which the condition would develop very diDerently (type I and II diabetes mellitus). With regard to the diagnosis alone, it makes no diDerence whether the predictor/marker is pathogenically involved or not, as long as the condition is precisely reported. Research aiming to identify easily measurable, aDordable disease predictors/markers could be especially useful for screening masses of people. This is a very important practical consideration, because in our overburdened healthcare systems, people, especially the underprivileged, are at a disadvantage to access diagnosis. A pathogenic involvement of predictors/markers is a bonus, as increased mechanistic understanding may be exploited therapeutically in the long run. For example, increased circulating levels of catecholamines and angiotensin II led to the development of new classes of medicines. Today, the countless human lives saved with beta blockers 2 and RAAS inhibitors 3 exemplify the potential of therapeutically targeting circulating messengers of harm.Our goal with the call "Endocrine insights into heart disease" was to attract work to help connect the dots on a landscape spanning from primary abnormalities, through their responses down to cardiovascular disease. The exciting studies in this topic cover an extended range of endocrine abnormalities, as briefly outlined below. Another important area revolves around body composition and metabolism. This is most timely due to the epidemic proportions obesity reaches, aDecting our society in complex, elusive but predominantly bad ways. The eDect is not simply incremental, however, i.e., the more obese the worse. The obesity paradox indicates that obese patients show improved outcomes in myocardial infarction, strokes, or heart failure, 5 whilst HDL-cholesterol protect against coronary heart disease), logistic analysis suggested that TyG, SII and SIRI were all independent risk factors for coronary heart disease in NAFLD patients. Further analysis indicated that these innovative biomarkers, individually and especially combined, have high predictive value, therefore may aid diagnostic eDorts. Our quest for the future will be to uncover the molecular underpinnings behind these exciting observations. Managing blood glucose is essential for reducing cardiovascular risks, but the intricate relationship between glycemic control and cardiovascular outcomes reveals deeper complexity, particularly involving diDerent lipoprotein fractions. In particular, uncontrolled lipoproteins, through their varying biological eDects, have been proposedto underlie divergent cardiovascular outcomes despite close glucose control. Studies highlight the distinct impacts of remnant-versus LDL-cholesterol in hypertension risk, demonstrate how apolipoprotein B mediates inflammation-related coronary heart disease, and emphasize the diDerential eDectiveness of hypoglycemic agents in slowing carotid artery thickening, an early marker of cardiovascular disease. These observations underscore the necessity to adopt a more nuanced approach beyond standard blood glucose control and take specific lipid profiles and inflammatory markers into consideration in therapeutic decisions for cardiovascular disease.Chen and colleagues (https://doi.org/10.3389/fendo.2023.1236404) took a deep dive into how SGLT2 inhibitors, originally designed to lower blood sugar in diabetes, protect patients with chronic kidney disease (CKD) from severe cardiovascular events.Remarkably, their analysis revealed that these medications significantly reduce hospital admissions for heart failure, the risks of heart-related and overall mortality. Even more reassuringly, these benefits did not come with increased rate of serious side-eDects or urinary tract infections, though they did see an uptick in reproductive tract infections. they established a direct connection between these benign tumors and elevated systolic blood pressure. This finding is particularly important for women's health, emphasizing the need for careful blood pressure monitoring in women with fibroids, especially during pregnancy. These findings also open the door to potential treatments that tackle uterine fibroids not just for their direct symptoms, but also as a means to control blood pressure.