Circadian rhythmic aspects of human cardiovascular function: a review by chronobiologic statistical methods

In this paper, evidence for circadian and other rhythms in cardiac and circulatory function is reviewed through the evaluation of earlier published data by least squares spectral and cosinor analyses. While the focus, herein, is on the documentation of temporal (mainly 24 h) changes in cardiovascular function of healthy human subjects using previously reported data, additional recent findings of ours from studies on patients as well as on human primates are included when relevant. Even though the aim of this paper is to present a comprehensive picture of circadian changes in cardiac and circulatory functions, it must be pointed out that data for this review were obtained from authors who studied individuals of various ages and levels of cardiovascular fitness and health. For example, studies cited pertain to investigations carried out on infants as well as elderly subjects, although most were carried out on healthy adults. Therefore, due to the wide range in age of subjects, and because of expected changes in cardiovascular function which occur with advancing chronologic age, even in healthy samples, simple and all inclusive statements about temporal characteristics, i.e. mesor, amplitude and acrophase for a given rhythm, can not be formulated indiscriminately for application to all individuals. Nonetheless, results of chronobiologic analyses on data obtained from several samples of healthy subjects, such as the variables of heart rate as well as systolic, diastolic and pulse pressure, reveal remarkable agreement for the aforementioned rhythmometric endpoints. Furthermore, several important aspects of cardiovascular function are yet to be studied for temporal variability. Because of this, several gaps exist, and a complete presentation of the temporal organization of the cardiovascular system is not possible at this time. However, this review does attempt to bring together relevant findings in order to present what is now known so that prospective investigations can be undertaken to verify previously reported findings, and more importantly, to provide new data on temporal aspects of cardiac and circulatory function not as yet studied. New investigations are needed to provide greater insight into the suspected existence of circadian susceptibilities to arrhythmias, coronary occlusion and stroke. If indeed such circadian or other susceptibility rhythms are documented, for example, as was the case for the nocturnal occurrence of asthma, the chronopharmacologic implications are obvious. The findings here reported documenting circadian rhythms in cardiovascular function, and those found by others on cardiac morbidity and mortality or on the manifestation of arrhythmias in recent myocardial infarct patients, suggest that treatment of heart disease be considered according to a possible circadian requirement for medications. The suspicion of circadian rhythms in cardiac dysfunction indicates the need for chronopharmacologic investigations of cardiac medications. Although some chronopharmacologic work has been initiated with respect to disorders other than cardiovascular ones, prospective studies must include aspects of the bioavailability of medication as well as the timing of treatments to achieve the best therapeutic advantage in patients with cardiac dysfunction. Chronopharmacologic methods with respect to synthetic corticosteroids have already proven useful in managing several steroid dependent illnesses. It is anticipated that chronopharmacologic investigations applied to cardiovascular disease will result in a re evaluation of dosage and administration schedules of medications with regard to circadian and possibly other period rhythms. (142 references are cited).