Irregular Sleep Patterns Increase Cardiovascular Disease Risk by 27%: Multi-Ethnic Study of Atherosclerosis (MESA) Extended Follow-Up

What Did the MESA Sleep Study Find About Irregular Sleep and Heart Disease?

The Multi-Ethnic Study of Atherosclerosis (MESA) is a long-running NIH-funded prospective cohort study that has followed 6,814 men and women from six US communities since 2000-2002. The MESA Sleep Ancillary Study, initiated in 2010-2013, equipped approximately 2,000 participants (mean age in the late 60s, diverse ethnic composition including White, African American, Hispanic, and Chinese American participants) with wrist-worn actigraphy devices for 7 consecutive days to objectively measure sleep timing, duration, and regularity. Analysis of this data, published in the Journal of the American Heart Association in 2020, linked actigraphy-derived sleep irregularity to cardiovascular outcomes.

Sleep regularity was quantified using the Sleep Regularity Index (SRI), a validated metric ranging from 0 (completely irregular — random sleep-wake pattern) to 100 (perfectly regular — identical sleep timing every day). The SRI captures variability in both sleep onset time and wake time across the monitoring period. Additionally, standard deviation of sleep duration was calculated. Participants were categorised into tertiles of sleep regularity. The most irregular sleepers had substantial night-to-night variability in sleep onset and duration, while the most regular sleepers had relatively stable patterns with variability typically under 30 minutes.

In multivariable Cox proportional hazards models adjusted for age, sex, race/ethnicity, educational attainment, BMI, smoking, alcohol, physical activity, total sleep duration, sleep quality (Pittsburgh Sleep Quality Index), obstructive sleep apnoea severity, diabetes, hypertension, dyslipidaemia, and use of sleep medications, participants in the most irregular sleep tertile had approximately 27% higher risk of incident composite cardiovascular events (including myocardial infarction, coronary heart disease death, and stroke) compared to the most regular tertile. The risk was also elevated for heart failure and stroke individually. Notably, the association was independent of total sleep duration — meaning that sleeping irregular hours was harmful even among those who averaged the recommended 7-8 hours per night. Subsequent analyses of the MESA cohort with longer follow-up have continued to support these findings.

Why Does Irregular Sleep Increase Cardiovascular Risk?

The relationship between sleep irregularity and cardiovascular disease is underpinned by circadian biology. The master circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates 24-hour rhythms in virtually every physiological system, including the cardiovascular system. Normal cardiovascular circadian rhythms include nocturnal blood pressure dipping (a 10-20% reduction during sleep, which gives the heart and vasculature a nightly recovery period), diurnal variation in heart rate and cardiac output, rhythmic fluctuations in sympathetic and parasympathetic nervous system activity, and circadian variation in platelet aggregability and fibrinolytic activity. Irregular sleep patterns disrupt these rhythms, a phenomenon termed "social jet lag" or circadian misalignment.

A landmark controlled laboratory study by Scheer et al. at Harvard, published in the Proceedings of the National Academy of Sciences in 2009, showed that simulated shift work-style circadian misalignment acutely elevated 24-hour blood pressure, increased inflammatory markers including C-reactive protein and interleukin-6, impaired glucose tolerance, and reversed the normal cortisol rhythm — all within just 8 days. In the MESA cohort, analyses have demonstrated that participants with the most irregular sleep had significantly higher odds of a non-dipping blood pressure pattern — a pattern strongly associated with target organ damage and cardiovascular events. Irregular sleepers also showed higher levels of inflammatory markers and greater insulin resistance at baseline, suggesting chronic low-grade inflammation and metabolic disruption.

Emerging evidence also links sleep irregularity to accelerated atherosclerosis. In the MESA cohort, irregular sleep was associated with higher coronary artery calcium (CAC) scores at baseline, a marker of subclinical atherosclerosis. Research published in cardiovascular journals has found that greater sleep duration variability is associated with faster progression of arterial wall thickening. These findings complement animal research showing that chronic circadian disruption in mouse models accelerates atherogenesis, promotes vascular smooth muscle cell proliferation, and impairs endothelial function. Together, the evidence suggests that sleep regularity — not just sleep duration — is a critical and previously underappreciated determinant of cardiovascular health.

How Can People Improve Sleep Regularity?

The most effective strategy for improving sleep regularity is maintaining consistent sleep and wake times, ideally within a 30-minute window, every day of the week including weekends and holidays. The common practice of "social jet lag" — sleeping significantly later on weekends to compensate for weekday sleep restriction — is itself a form of circadian disruption. Research by Roenneberg and colleagues has demonstrated that social jet lag is independently associated with adverse cardiovascular and metabolic outcomes, with each hour of social jet lag increasing the risk. The MESA data reinforced this finding: participants who maintained consistent sleep times throughout the week had the lowest cardiovascular risk, while those with substantial weekend/weekday misalignment had significantly elevated risk.

Light exposure is the most powerful synchroniser (zeitgeber) of the circadian clock. Exposure to bright light (at least 2,500 lux, ideally 10,000 lux) within the first hour after waking helps anchor the circadian rhythm and promotes consistent sleep onset timing the following night. Conversely, exposure to bright light (particularly blue-enriched light from screens) in the 2-3 hours before bedtime delays melatonin secretion and shifts the circadian clock later, making it harder to fall asleep on time. Research suggests that reducing evening blue light exposure — either by using blue light-blocking glasses or enabling device night mode filters — can modestly improve sleep onset latency and total sleep time. The American Academy of Sleep Medicine recommends dimming lights and avoiding screens for at least 30 minutes before bed, or using blue light filters if screens cannot be avoided.

Regular meal timing also reinforces circadian rhythms, as peripheral clocks in the liver, gut, and pancreas are strongly entrained by food intake. Eating at consistent times each day — and avoiding late-night eating (within 2-3 hours of bedtime) — supports alignment between the central clock and peripheral metabolic rhythms. Regular physical activity, particularly when performed in the morning or early afternoon, promotes sleep quality and circadian entrainment. Caffeine should be avoided for at least 6 hours before bedtime; a study by Drake et al. published in the Journal of Clinical Sleep Medicine in 2013 demonstrated that caffeine consumed 6 hours before bed still significantly reduced total sleep time. For individuals with persistent sleep irregularity despite behavioural strategies, cognitive behavioural therapy for insomnia (CBT-I) has strong evidence for improving sleep patterns and is recommended as the first-line treatment for chronic insomnia by the American College of Physicians and the European Sleep Research Society.

What Is the Ideal Sleep Schedule for Heart Health?

The MESA data, combined with other large cohort studies, paint a clear picture of the sleep pattern associated with the lowest cardiovascular risk: 7-8 hours of total sleep duration, with a consistent sleep onset time between approximately 10:00-11:00 PM, minimal night-to-night variability (less than 30 minutes), and good sleep efficiency (85% or above, meaning that 85% of time in bed is actually spent asleep). In the MESA analysis, participants who simultaneously had regular sleep and optimal duration had the lowest cardiovascular event rates, while those with both irregular sleep and short duration had substantially higher event rates.

A complementary study from the UK Biobank, published in European Heart Journal – Digital Health in 2021 by Nikbakhtian et al., analysed accelerometer data from approximately 88,000 participants and found that sleep onset between 10:00-11:00 PM was associated with the lowest cardiovascular risk. Falling asleep before 10:00 PM or after 11:00 PM was associated with modestly increased risk, while falling asleep after midnight was associated with approximately 25% increased risk compared to the 10:00-11:00 PM reference group. This is consistent with the alignment of sleep timing to the natural light-dark cycle and endogenous circadian rhythm.

For shift workers — who represent approximately 15-20% of the workforce in industrialised countries and face inherent challenges in maintaining regular sleep — the cardiovascular risks are well-documented. A systematic review and meta-analysis by Vyas et al. published in the BMJ in 2012 found that shift work was associated with a 23% increased risk of myocardial infarction. While some circadian disruption is unavoidable in shift work, strategies to mitigate harm include rotating shifts in a clockwise direction (morning → evening → night), using strategic bright light exposure to shift the circadian clock toward the work schedule, taking planned naps before and during night shifts, and ensuring that sleep periods after night shifts are protected from light and noise. For non-shift workers, the evidence overwhelmingly supports that a consistent, well-timed sleep schedule is one of the most modifiable cardiovascular risk factors available — arguably as important as the well-established pillars of diet, exercise, and not smoking.