Commentary on the Biological Rhythmicity of Coronary Disease.

All human organic functions show diurnal variation or regular changes from day to night (Van Cauter, 1989) with circadian rhythms having evolved as responses to environmental fluctuations. Health risks may therefore stem from alteration of the “…biological time-structure or chronobiology.” (Gugini, 1990). Therefore an “…acquired endogenous temporal programme…” (Van Cauter, 1989) from the “…periodicity of the environment…” that “…acts as a synchronizing agent for the endogenous circadian rhythmicity.”

In the pathological syndromes of CHD there is a circadian pattern of episodic cardiac ischaemia. There is a peak in episodic ischaemia during morning waking hours and 24 hour ECG monitoring has shown that

…the distribution of ischaemic episodes showed a similar circadian variation to the reported distribution of acute myocardial infarction and sudden death.” (Mulcahy, 1988; Muller, 1987). Ischaemic episodes show circadian rhythmicity (Rocco, 1987; Quyyumi, 1985) with most episodes between 07.30 am and 19.30 pm with morning and evening (lesser) peaks (Mulcahy, 1988).

A circadian rhythm for episodic ischaemia is shown by the existence of nocturnal and daytime aspects of CHD (Rocco, 1987) and in severe CHD …the mechanisms producing nocturnal resting ischaemia were apparently similar to those during daytime exertion: increased myocardial oxygen demand not coronary spasm seemed responsible for most of the periods of nocturnal ischaemia.” (Quyyumi, 1984), with episodes of ischaemia during sleep occurring particularly between 4.00 am and 6.00 am (Selwyn, 1978). In addition – blood pressure falls during sleep (Millar-Craig, 1978).

Transient asymptomatic (‘silent’) ischaemia shows a circadian rhythm similar to that of the ‘total ischaemic burden’ (Mulcahy, 1988). Most episodes occur between 06.00 am and 12.00 noon (unlike SCD with a rhythm

of 18.00 pm to 22.00 pm), being least frequent between 24.00 midnight and 06.00 am (Campbell, 1986; Coy, 1987). Such diurnal variation shows a steep rise to a maximum around 10.00 am, most episodes accompanied by heart rate increase but few are due to coronary artery spasm or increased vasomotor tone (McCarthy, 1987). In general silent ischaemia shows a circadian peak in incidence on waking and the few hours thereafter (Campbell, 1988), which parallels the circadian incidence of AMI, even though ‘silent’ ischaemia shows individual variation (Deanfield, 1983; Nabel, 1988). Blood pressure is lowest at 03.00 am with elevation during early hours before waking (Millar-Craig, 1978).

The circadian rhythm shown by acute myocardial ischaemia (angina pectoris) supports the demand theory because morning waking hours are a time of (a) increased myocardial demand, (b) peak in heart rate and BP,(c) catecholamine release (Mulcahy, 1988). The peak morning period for angina pectoris parallels a similar pattern shown by haemodynamic (BP, heart rate) measurements (Millar-Craig, 1978). Variant angina and angina at rest are commonest during the early morning (Mulcahy, 1985) suggesting that supply reduced by coronary artery spasm may be the underlying cause, possibly involving a role for intracardiac catecholamine release (Kattus,1976), with most cases of vasospastic closure occurring in association with atheromatous plaques of both mild and severe forms (McAlpin, 1980).

It is thought that vasoconstrictor stimuli and ‘cold pressors’ are involved in precipitating critical vasoconstriction and ischaemia and these factors vary between the two groups – nocturnal and daytime (Crea,1982). It is known that there is an increase in sympathetic nervous activity during the morning waking hours (Muller, 1987), and this may well predispose to “…coronary as well as systemic vasoconstriction” and is possibly one more causal factor for cardiac ischaemia (Mulcahy,1988). A similar circadian pattern is shown by catecholamines (Turton,1974). Heart rate is increased by reflexes and circulatory catecholamines during exercise and stress – with catecholamines increasing contraction velocity (Bailey, 1984) and explains how angina can be induced by effort and emotion.


The circadian rhythm for AMI (Muller, 1985) shows a peak incidence of infarction around 10.00 am (Millar-Craig, 1978) with the circadian rhythm for SCD (Willich, 1987; Muller, 1987) showing an evening peak between 18.00 pm and 22.00 pm (Moss, 1980). Heart rate shows a similar circadian pattern to episodic ischaemia (Millar-Craig, 1978) and other haemodynamic measurements including blood flow and BP (Mulcahy, 1988). Coronary blood flow exhibits circadian variation with flow 12.8% greater after 12.00 noon than during the morning (Fugita, 1987). Heart rate achieves a mid-day maximum and then falls to reach a nadir during sleep (Millar-Craig, 1978). BP has a circadian early afternoon peak in adults (Gugini, 1990) and like heart rate BP peaks mid-morning and falls during the day (Millar-Craig, 1978).

Diurnal variations involve the endocrine system and numerous other physiological variables including BP, temperature, cardiac output (Van Cauter, 1989). SCD (Muller, 1987) and AMI (Muller, 1985) exhibit rhythms that also correspond with patterns of blood coagulation (Mulcahy, 1988). Circadian rhythms for coagulation indices shown by an increase in platelet stickiness with decreased fibrinolytic activity in the morning (Willich, 1987; Tofler, 1987) with control of BP circadian rhythmicity maintained through neurohormonal mechanisms (Millar-Craig, 1978). Serum cholesterol levels vary from a nadir of 4.88 mmol/1 (189 mg/dl) between 10.00 and 11.00 am to a peak of 5.45 mmo1/1 (211 mg/dl) between 15.00 and 16.00 pm, with a lower mid-peak around 12.00 noon (Natelson, 1988), and in addition TC levels showed a cyclical periodicity of 50 minutes.

References – to follow.

Appendix 179. MPhil Thesis: Population Variation for Risk Factors in Ishaemic Heart Disease. CNAA. Oxford Polytechnic and Oxford Brookes University. September, 1992.


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