Hydrogen sulfide and cardiovascular disease: Doubts, clues, and interpretation difficulties from studies in...

Hydrogen sulfide (H₂S) represents one of the main pollutants originating from both geologic phenomena such as volcanoes, geysers, fumaroles and hot springs, and geothermal plants that produce heat and electricity. Many increasing data suggest that H₂S retains a variety of biological properties, and modulates many pathways related to cardiovascular pathophysiology although its role as beneficial/adverse determinant on cardiovascular disease (CVD) is not clearly established. In this review, the current knowledge on the association between H₂S exposure and risk of CVD in geothermal areas has been examined. The few epidemiological studies carried out in geothermal areas suggest, in some cases, a protective role of H₂S towards CVD, while in others a positive association between exposure to H₂S and increased incidence of CVD. Most of the studies have an ecological design that does not allow to produce evidence to support a causal relationship and also often lack for an adequate adjustment for individual CVD risk factors. The review has also considered the potential role of two other aspects not sufficiently explored in this relationship: the production of endogenous H₂S that is a gasotransmitter producing beneficial effects on cardiovascular function at low concentration and the intake of H₂S-releasing drugs for the treatment of patients affected by hypertension, inflammatory diseases, and CVD. Thus, a threshold effect of H₂S and the shift of action as beneficial/adverse determinant given by the synergy of exogenous exposure and endogenous production cannot be excluded. In this complex scenario, an effort is warranted in the future to include a more comprehensive evaluation of risk for CVD in relation to H₂S emissions, especially in geothermal areas.