title: Twenty-four-hour patterns in occurrence and pathophysiology of acute cardiovascular events and ischemic heart disease.
abstract: The scientific literature clearly establishes the occurrence of cardiovascular (CV) accidents and myocardial ischemic episodes is unevenly distributed during the 24 h. Such temporal patterns result from corresponding temporal variation in pathophysiologic mechanisms and cyclic environmental triggers that elicit the onset of clinical events. Moreover, both the pharmacokinetics and pharmacodynamics of many, though not all, CV medications have been shown to be influenced by the circadian time of their administration, even though further studies are necessary to better clarify the mechanisms of such influence on different drug classes, drug molecules, and pharmaceutical preparations. Twenty-four-hour rhythmic organization of CV functions is such that defense mechanisms against acute events are incapable of providing the same degree of protection during the day and night. Instead, temporal gates of excessive susceptibility exist, particularly in the morning and to a lesser extent evening (in diurnally active persons), to aggressive mechanisms through which overt clinical manifestations may be triggered. When peak levels of critical physiologic variables, such as blood pressure (BP), heart rate (HR), rate pressure product (systolic BP × HR, surrogate measure of myocardial oxygen demand), sympathetic activation, and plasma levels of endogenous vasoconstricting substances, are aligned together at the same circadian time, the risk of acute events becomes significantly elevated such that even relatively minor and usually harmless physical and mental stress and environmental phenomena can precipitate dramatic life-threatening clinical manifestations. Hence, the delivery of CV medications needs to be synchronized in time, i.e., circadian time, in proportion to need as determined by established temporal patterns in risk of CV events, and in a manner that averts or minimizes undesired side effects.
authors.affiliation: Section of Clinica Medica, Department of Clinical and Experimental Medicine, University of Ferrara, Via Savonarola 9, Ferrara, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Manfredini
authors.forename: Benedetta
authors.initials: B
authors.lastname: Boari
authors.forename: Raffaella
authors.initials: R
authors.lastname: Salmi
authors.forename: Fabio
authors.initials: F
authors.lastname: Fabbian
authors.forename: Marco
authors.initials: M
authors.lastname: Pala
authors.forename: Ruana
authors.initials: R
authors.lastname: Tiseo
authors.forename: Francesco
authors.initials: F
authors.lastname: Portaluppi
mesh_terms: D001014:Aortic Aneurysm / Q000175:diagnosis / Q000503:physiopathology; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000503:physiopathology; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D002317:Cardiovascular Agents / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000503:physiopathology; D002940:Circadian Rhythm; D006339:Heart Rate; D006801:Humans; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D020521:Stroke / Q000175:diagnosis / Q000503:physiopathology; D054549:Takotsubo Cardiomyopathy / Q000175:diagnosis / Q000503:physiopathology; D013997:Time Factors
chemical_list: D002317:Cardiovascular Agents