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Take a look at a selection of our recent media coverage:
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
2nd December 2022
HDL cholesterol is generally considered to be protective against coronary heart disease (CHD) but a recent analysis that included both Black and White patients suggests that higher levels offer no protection in either race with an elevated CHD risk due to low levels only relevant for White individuals.
Globally, coronary heart diseases were estimated to kill 17.9 million people in 2019, which represents 32% of all global deaths, with 85% of deaths due to heart attack and stroke. Since the early 1970’s, there has been a well-established and inverse relationship between plasma high-density lipoprotein (HDL) cholesterol and CHD risk. However, whether this relationship remains for different ethnicities is uncertain. It is known for example, that after accounting for social determinants of health and other risk factors, Black patients have a similar risk of a fatal CHD to White patients, but that the risk for a nonfatal CHD is consistently lower for Black people. The underlying reasons behind this difference are unclear and have been further confounded by the somewhat paradoxical observation that low levels of HDL cholesterol are associated with a reduced risk of incident CHD in black participants.
In trying to better understand the relationship between HDL cholesterol and incident CHD, a team of US researchers turned to data collected in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, designed to examine underlying racial and regional differences in stroke and mortality. The researchers selected a cohort without baseline CHD and for whom a wide range of clinical and demographic factors were collected. The cohort was followed over time and the number of incident CHD (i.e., definite or probable nonfatal myocardial infarction or CHD death) were recorded.
HDL cholesterol and CHD events in Black and White patients
A total of 23,901 participants with a mean age of 64.1 years (58.3% female) and of whom, 57.7% self-identified as White were included in the analysis and followed for a median of 10.7 years. During the follow-up there were 1,615 CHD events of which 41.1% occurred in Black participants and 45.5% in women.
When analysing the relationship between CHD events and plasma LDL cholesterol in fully adjusted models, for every 1 standard deviation increase in LDL levels, there was a modest increase in CHD risk (Hazard ratio, HR = 1.10, 95% CI 1.05 – 1.17). Similarly, for triglyceride levels, there was also a modest increase in CHD risk (HR = 1.05, 95% CI 1.01 – 1.10). However, in fully adjusted models, there was a non-significant association between HDL cholesterol (HDL-C) levels and CHD risk (HR = 0.95, 95% CI 0.89 – 1.02).
But when researchers examined the relationship between HDL-C and CHD risk stratified by race, they found something unusual. As might be expected based on the currently known relationship, a low HDL-C level was associated with an increased risk of CHD, but this was only significant for White patients (HR = 1.22, 95% CI 1.05 – 1.43). Among Black patients the relationship was not significant (HR = 0.94, 95% CI 0.78 – 1.14). Furthermore, a high HDL-C level was not protective in either White (HR = 0.96, 95% CI 0.79 – 1.16) or Black (HR = 0.91, 95% CI 0.74 – 1.12) patients.
Based on these findings, the authors concluded that current high-density lipoprotein cholesterol–based risk calculations could lead to inaccurate risk assessment in Black adults.
Zakai NA et al. Race-Dependent Association of High-Density Lipoprotein Cholesterol Levels With Incident Coronary Artery Disease. J Am Coll Cardiol 2022
10th November 2022
Patients with thyroid cancer (TC) have a greater risk of developing coronary heart disease and in those under 65 years of age, this elevated risk persists for at least five years after their cancer diagnosis according to an observational study by Taiwanese researchers.
In 2020, the global estimated rate of thyroid cancer was 10·1 per 100 000 women and 3·1 per 100 000 men, although mortality rates were lower at 0·5 per 100 000 and 0·3 per 100 000 for women and men respectively. Surgery is the mainstay of treatment in nearly every case of thyroid cancer although radiotherapy can also be used. If the thyroid is removed, then patients will require life-long therapy with levothyroxine both to replace the hormone and lower the risk of cancer recurrence. However, long-term use of levothyroxine may cause marked impairment of cardiac functional reserve and physical exercise capacity. Whether these changes increase the subsequent risk of cardiovascular disease remains uncertain with some evidence that such patients have a higher incidence of cardiovascular disease morbidity. In contrast however, other work has shown that the incidence of cerebrovascular disease, cerebral infarction, ischaemic heart disease, ischaemic heart attack and heart failure are no different between those with TC and the general population.
With some uncertainty over the relationship between TC and the risk of cardiovascular diseases, in the current study, the Taiwanese researchers turned to data contained within a nationwide population-based cohort to retrospectively examine this relationship. They chose a baseline date for their analysis as the time when TC patients underwent a thyroidectomy but excluded those aged < 20 and > 85 years and anyone with a history of coronary heart disease (CHD) or atrial fibrillation. They set the primary endpoint of interest as hospitalisation for CHD defined in terms of fatal and non-fatal CHD. Secondary outcomes included ischaemic stroke (IS) that required hospitalisation and atrial fibrillation, which again required hospitalisation. The researchers calculated a standardised incidence ratio (SIR) as the ratio of observed to expected CHD cases, stratified by age and gender within the general population.
Thyroid cancer and risk of coronary heart disease
A total of 4,274 individuals who had thyroid cancer without CHD and a mean age of 49 years (24.4% male) were included in the analysis and followed-up for a mean of 3.5 years.
During follow-up, there were 69 CHD events in those with TC and the SIR was significantly higher than expected in the age-standardised population (SIR = 1.57, 95% CI 1.2 – 1.93). However, the rate of IS was not significantly different (SIR = 0.74, 95% CI 0.47 – 1), neither was the incidence of cardiovascular disease (SIR = 0.88, 95% CI 0.70 – 1.05) or atrial fibrillation (SIR = 0.74, 95% CI 0.42 – 1.06).
When researchers considered the SIR over time, particularly among those under 65 years of age, the elevated risk remained significant, 5 years after the date of their TC diagnosis (SIR = 2.08, 95% CI 1.5 – 2.66) although it was non-significant among those over 65 years of age (SIR = 1.0, 95% CI 0.57 – 1.42).
The authors concluded that thyroid cancer patients had a greater risk of CHD than the general population without the cancer and that this risk persisted for at least 5 years. They called for future research to further investigate this observed association.
Tsai MC et al. Association between thyroid cancer and cardiovascular disease risk: a nationwide observation study. Sci Rep 2022
17th June 2022
Patients with coronary heart disease (CHD) who continue to be physically active over time and even those who reduce their activity, have a significantly lower risk of all-cause mortality compared to those who remain physically inactive. This was the key finding from a meta-analysis by a team of researchers from Switzerland and Colombia.
Cardiovascular diseases are the leading cause of mortality around the world with an estimated 17.9 million deaths in 2019 and which represented 32% of all global deaths. One modifiable risk factor for cardiovascular disease (CVD) is physical activity and in a 2017 study found that a higher level of recreational and non-recreational physical activity was associated with a lower risk of all-cause mortality and CVD events.
However, whilst there are clear benefits from increased levels of physical activity with respect to all-cause mortality among those with CHD, what is less clear, is the impact of changes in physical activity over time. For the present study, the researchers performed a systematic review and meta-analysis to examine the association between longitudinal trajectories of physical activity and both all-cause mortality and cardiovascular disease mortality in those with CHD. The team included studies with a longitudinal design in adults with CHD and which provided data on all-cause and CVD mortality. For the purposes of the analysis, the researchers examined the changes in all-cause mortality by different levels of reported physical activity trajectories. For example, those who remained inactive, those who increased their physical activity and finally individuals who decreased their activity level over time. For the analysis, hazard ratios were calculated and regression models were adjusted for age, gender, ethnicity, smoking status, alcohol intake and co-morbidities. All of the studies assessed physical activity using validated questionnaires.
All-cause mortality and physical activity trajectories
A total of 9 articles were included in the final analysis, all of which were prospective in nature with 33,576 patients with an overall mean age of 62.5 years and the proportion of women ranging from 18 to 56%.
Compared to those who remained inactive over time, the risk of all-cause mortality was 50% lower among those who remained active (hazard ratio, HR = 0.50, 95% CI 0.39 – 0.63), 45% lower for those who increased their level of activity (HR = 0.55, 95% CI 0.44 – 0.70). Moreover, even among those who had been active but who became less active, there was still a 20% lower all-cause mortality risk (HR = 0.80, 95% CI 0.64 – 0.99).
These reductions in risk were similar for cardiovascular mortality. For example, it was 51% lower for those who remained active (vs inactive) however, it became non-significant for those whose activity levels had reduced over time (HR = 0.91, 95% CI 0.67 – 1.24).
The authors concluded that there was a possible protective mortality benefit of either increased or continued activity among patients with CHD and suggested that physical activity trajectories should be considered in clinical practice.
Gonzalez-Jaramillo N et al. Systematic Review of Physical Activity Trajectories and Mortality in Patients With Coronary Artery Disease J Am Col Cardiol 2022