Robert Daly / Stone / Getty A man being revived by defibrillator machine.

Related The Early Morning Heart Attack

Heart disease, including heart attack, is the world's No. 1 killer. A person's risk of heart attack depends mostly on a familiar repertoire of factors: exercise, smoking, diet, weight, genes. But our bodies' circadian rhythms also play a role, leaving us more prone to injury during certain hours than others. If you're guessing that the danger zone comes at the end of a stressful workday, guess again. Here to explain is Roberto Manfredini, professor of internal medicine at the University of Ferrara in Italy.

Q: What time of day am I most likely to have a heart attack?

A: The most dangerous times for heart attack and for all kinds of cardiovascular emergency  including sudden cardiac death, rupture or aneurysm of the aorta, pulmonary embolism and stroke  are the morning and during the last phase of sleep. A group from Harvard estimated this risk and evaluated that on average, the extra risk of having a myocardial infarction, or heart attack, between 6 a.m. and noon is about 40%. But if you calculate only the first three hours after waking, this relative risk is threefold.

The cardiovascular system follows a daily pattern that is oscillatory in nature: most cardiovascular functions exhibit circadian changes (circadian is from the Latin circa and diem, meaning "about one day"). Now, a heart attack depends on the imbalance between increased myocardial oxygen demand (i.e., a greater need for oxygen in your heart) and decreased myocardial oxygen supply  or both. And unfortunately, some functions in the first hours of the day require more myocardial oxygen support: waking and commencing physical activities, the peak of the adrenal hormone cortisol [which boosts blood-pressure and blood-sugar levels] and a further increase in blood pressure and heart rate due to catecholamines (adrenaline and noradrenaline), which show a peak when you wake up. All those factors lead to an increase of oxygen consumption but at the same time contribute to the constriction of vessels. So you have reduced vessel size and reduced blood flow to the coronary vessels.

You have to remember that blood coagulation is important in the genesis of what we call thrombi, the blood clots that can block the blood vessels and cut off supply to the heart. When we wake up, platelets, the particles in the blood that make thrombi, are particularly adhesive to the vessels. Usually we have an endogenous system  it's called fibrinolysis  to dissolve the thrombi. But in the morning, the activity of our fibrinolytic system is reduced. So we have a greater tendency to make thrombi that can occlude the coronary vessels. This contributes to further reduction of coronary blood flow. Thus, at the same time that you need more blood flow, you have less.

All these changes, however, probably are not so harmful in healthy people. But for a person with a plaque in the coronary vessel, if these changes occur at the same time and peak at the same time, the final result is a higher risk of heart attack during that specific window of morning hours.

Why is the risk also higher during the last part of sleep? Usually, during the night, the cardiovascular system is "sleeping," which is characterized by low blood pressure and heart rate. But the last stage of sleep  REM, or rapid eye movement, sleep [when we believe most dreaming occurs]  is a risk period for cardiovascular emergencies because when you dream, you have a dramatic increase of activity of the autonomic nervous system  even more than when you are awake. Probably each of us can remember waking up in the morning sometimes feeling very tired. That's because during that stage of dreams, we were running or facing some danger. Your heart was running, so it was consuming oxygen. And for similar reasons to those when you're awake, that activity is risky if you don't have a good vessel system.

It's probably difficult for people to minimize the effects of their own biological rhythms. For example, you cannot avoid your morning risk by simply waking up later. Some researchers have tried an experimental model, in which people were instructed to stay in bed for four hours after they woke up before rising. But the same pattern simply occurred four hours after waking, because the risk is linked to our activities. We can't be afraid of the catecholamines and the peak in blood pressure in the morning. It's part of our physiology. And for healthy people, it's not a problem.

It's important for doctors, however, to remember this risk when we give therapy. Usually people take hypertensive drugs in the morning, when they wake up. But this is already the higher-risk period  so is the last hour of activity of the pill they have taken the day before [and not all pills give 24-hour coverage]. We have to be sure that the pill we're prescribing is still active when patients need it most. It's not as easy as simply asking patients to take pills before bed instead of first thing in the morning, because during sleep we have a low heart rate and blood pressure. If you lower your blood pressure too much during the night, you risk reducing blood supply to the brain, and that can be harmful too.