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9th January 2023
Infection with herpes zoster is associated with a higher long‐term risk of a major cardiovascular event such as a stroke and the development of coronary heart disease, according to an analysis of three large, prospective studies by researchers from Harvard Medical School, Boston, US.
Herpes zoster (HZ) occurs after reactivation of the varicella-zoster virus which is both persistent and clinically dormant, within spinal ganglia or cranial sensory nerves following an initial infection with varicella. In fact, HZ strikes millions of older adults annually worldwide and disables a substantial number of them via post-herpetic neuralgia. Moreover, in recent years, emerging evidence suggests that HZ infection leads to 1.3 to 4-fold increased risk of cerebrovascular events with a higher risk among adults under 40 years of age and within one year after an HZ episode. However, what remains unclear, is the long‐term association between HZ infection and the risk of adverse cardiovascular events or cardiovascular disease.
In the present study, US researchers investigated the longitudinal association of herpes zoster (or ‘shingles’) and the risk of stroke or coronary heart disease (CHD) among participants in 3 large US cohorts; the NHS (Nurses’ Health Study), NHS II (Nurses’ Health Study II), and HPFS (Health Professionals Follow-Up Study). Within the three cohorts, participants were asked to self-report about clinician‐diagnosed shingles and the year of diagnosis. The primary exposure for the study was categorised according to time (in years) since the participant’s HZ event and those with no history of HZ served as the reference group. The researchers then categorised the time since HZ as never, 1 to 4 years since infection, 5 to 8 years, 9 to 12 years and ≥13 years. In their analysis, adjustment were made for several factors that could potentially be related to HZ and stroke or CHD, including age, race, smoking history, body mass index, waist circumference etc.
Herpes zoster infection and cardiovascular events
The study included data on 79,658 women in the NHS, 93,932 in the NHS II and 31,440 men in the HPFS (2004-2016), without prior stroke or CHD. During >2 million person-years of follow-up, 3603 incident stroke and 8620 incident CHD cases were documented.
In a pooled analyses and compared to those without a history of HZ infection, the multivariable-adjusted hazard ratio (HR) for stroke was non-significant for those with 1 to 4 years since HZ infection (HR = 1.05, 95% CI 0.88 – 1.25). However, the associations became significant as the duration from infection increased. For example, among those with 5 to 8 years since HZ, the hazard ratio was 1.38 (95% CI 1.10 – 1.74) and 1.28 (95% CI 1.03 – 1.59) among those with for 9 to 12 years since HZ. Interestingly, the association became non-significant among those with ≥13 years since HZ (HR = 1.19, 95% CI 0.90 – 1.56).
When considering CHD, the corresponding multivariable-adjusted hazard ratios were similar, e.g. 1.25 (95% CI 1.07 – 1.46) for 9 to 12 years and, as with stroke, the risk of CHD became non-significant after ≥13 years (HR = 1.00, 95% CI 0.83 – 1.21).
The authors concluded that herpes zoster is associated with a higher long-term risk of a major cardiovascular event, underscoring the importance of prevention of infection.
Curhan SG et al. Herpes Zoster and Long-Term Risk of Cardiovascular Disease. J Am Heart Assoc. 2022