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Focus on cardio-oncology and cardio-toxicity with Dr Rebecca Dobson

17th February 2024

Speaking at Hospital Healthcare Europe’s Clinical Excellence in Cardiovascular Care event, Dr Rebecca Dobson discussed the need and demand for cardio-oncology services, how they’ve developed over time and the current state of play in this evolving field, as well as providing an overview of cardio-toxicity.

A decade or two ago, there was no such thing as cardio-oncology, and Dr Rebecca Dobson, consultant cardiologist specialising in imaging and cardio-oncology at Liverpool Heart and Chest Hospital and the Clatterbridge Cancer Centre, says things have ‘progressed somewhat from the days when all you were interested in was an ejection fraction’.

In fact, specialists like Dr Dobson – who also heads up her regional cardio-oncology service – now combine their wide-ranging cardiology expertise with close multidisciplinary working to allow cancer patients to receive the best possible treatments safely and minimise cancer therapy-related cardio-toxicity across the entire continuum of cancer care.

What is the role of cardio-oncology in contemporary medicine?

For a long time, everyone’s known that certain cancer therapies can affect the heart and, traditionally, these patients have been seen in heart failure clinics because we were looking for left ventricular systolic dysfunction.

But as the global burden of cancer has increased, and the treatments that we use to treat these cancers have increased, we’re seeing more and more patients with cancer who are exposed to more and more potentially cardio-toxic therapies, who would then potentially require the input of a cardiologist to maximise their cardiac health.

Previously, if a patient had cancer and was treated with cardio-toxic treatment, unfortunately, their outlook would have been relatively poor and a cardiologist would very rarely have to get involved with that patient’s treatment. Whereas now patients are living a lot longer with the effects of the cancer therapies.

And I think this is a real testament to the advances within oncology – the field is advancing at a really rapid pace, which is great for patients from a cancer point of view but it has important implications from a cardiology point of view.

What we don’t want to do with patients is cure their cancer and forget about their heart because it would be a real tragedy to cure someone’s cancer and then they end up having an avoidable cardio-toxicity.

It’s really important that we think about these patients’ cardiovascular health, and I think in the past, as cardiologists we’ve often almost shied away from patients with cancer. And I think we’ve probably done some of our patients a bit of a disservice because there is a lot we can do, and we need a rapid response service so that we can see these patients quickly.

What do you see as the role of the cardio-oncologist?

I think a lot of patients worry that when they come to a cardio-oncology clinic, that we’re going to put up barriers and say, ‘you can’t have your cancer therapy’. And sometimes we do have to do that, but it’s actually quite rare. Far more often, we can facilitate the necessary cancer therapy by optimising the cardiac side of things.

Then at the other end of the spectrum, we look after patients who have been happily cured of their cancer, but who are at risk of late effects. So, these will be, perhaps, children or young adults who’ve had cancer at a young age and had lots of cardio-toxic therapy, but who are living with that increased risk for the rest of their lives.

These are the patients that we really don’t want to lose track of – they need to stay on someone’s radar so that we can screen them at regular intervals and pick up any issues at the earliest possible point.

How do you manage demand for the cardio-oncology service and support patient care?

One of the service fundamentals, I would say, is that we provide prompt cardiology input. At the moment, the way we’ve set our service up means we can see patients within a week to two weeks, so it’s a very responsive service. There’s lots of moving patients around to try and make sure that the most urgent patients get seen most quickly.

It also has to be based upon collaborative, multidisciplinary working. There is no point me sitting in my hospital at Liverpool Heart and Chest doing my cardiac thing with the patients and not talking to the oncologist who’s three miles up the road. It’s all about efficient communication with the oncologists, with the surgeons, anaesthetists, whoever it is who’s involved in that patient’s care. It is a truly multidisciplinary specialty, and I think it has to be because these are complicated patients and the last thing we want to do is make a decision that denies someone that a potentially life-saving cancer therapy.

I’d like to think that we offer a really holistic approach to patient care. And I say that with a smile on my face as a cardiologist because I know we’re not known for that – cardiologists will often focus on the heart and nothing but the heart. And I think these patients have such a lot going on with them, it’s really important that we recognise that within the service and work with other specialties to make sure we treat all of the patient and not just their heart.

Traditionally, cardiologists and oncologists have not worked closely together; we speak different languages. Certainly, when I when I first started in this subspecialty, I had no idea what a TKI was or what CHOP meant. And similarly, cardiologists have their own language talking about DAPT and TAVI and GLS. It’s really important that we try and understand where each other is coming from, understand clinical priorities, and have that collaborative approach to bridge the gap between the two specialties.

I’d recommend reading the 2022 ESC guidelines on cardio-oncology. It’s a really comprehensive document that covers lots of different types of cardio-toxicity.

It also includes a diagram that illustrates quite nicely the role of cardio-oncology care pathway. It’s important that we see patients at the beginning of their diagnosis, we follow them through their treatment, and we follow them up in the long term.

The diagram really illustrates the importance of risk stratifying patients at baseline and tailoring their cardio-oncology input accordingly.

Tell us more about your cardio-oncology service and day-to-day work

I set up the service in 2019 and at that point, we were doing two cardio-oncology clinics a month. Now we’re running two and a half clinics a week and are looking to increase that further because the demand is there.

I also do a weekly ward round at Clatterbridge Cancer Centre, our local cancer hospital, which provides really useful input to the oncologists and radiotherapists there for inpatients with cancer who have a cardiac issue like atrial fibrillation or high blood pressure.

We run four weekly cardio-oncology echo lists and a weekly cardio-oncology MDT, which we do virtually and that’s probably the most important part of the service. Any patient who is particularly complex, where we’ve got important clinical decisions to make, will come through our MDT, and that will always have oncology, cardiology, radiology and usually cardiothoracic surgical representation.

We’ve recently taken over surveillance and management of all the region’s carcinoid heart disease patients. We’ve set up immunotherapy baseline screening programme so we can try and detect cardio-toxicity at an early stage. And we’ve worked with the radiotherapists at Clatterbridge to educate them and enable them to do their own cardiac monitoring for patients with cardiac devices when they’re receiving radiotherapy.

We’re quite busy, and we’re getting busier all the time, which is why we’re looking to bring in a cardio-oncology nurse specialist as soon as possible. We’re going to be running a physiologist-led echo clinic for those patients that don’t need to see a cardiologist. And we are also looking to improve our baseline ECG review for patients who are receiving immunotherapy.

What is cardio-toxicity and how does it manifest?

I could talk for days about this! In the past, we’ve always thought about left ventricular systolic dysfunction being what we mean when we say ‘cardio-toxicity’. Certainly, a lot of what I deal with is cardiac dysfunction or heart failure, but it’s not the only thing I deal with.

It’s a real broad church of different manifestations of cardio-toxicity, which I think is probably another reason why I really enjoy my job – it keeps me on my toes. The more I do in this field, the more I realise that I’ve got a lot to learn and I’m always coming across another cardio-toxicity with a different type of drug.

From a cardiac dysfunction point of view, the drugs that we worry about the most are anthracyclines, the anti-HER2 therapies like herceptin.

From an arrhythmia point of view, oncologists do use arsenic to treat some types of cancers, and arsenic and tyrosine kinase inhibitors (TKIs) are very good at causing atrial fibrillation and arrhythmias. And TKIs and mTOR inhibitors are the main offenders for causing hypertension.

For vascular toxicity, it’s usually the drugs that we use to treat bowel cancer so 5FU, which can cause coronary artery spasm, which can be incredibly dramatic. We’ve seen patients who’ve presented with the peri-arrest with ST elevation that’s all settled down as that spasm is released.

And myocarditis is usually caused by checkpoint inhibitors or immunotherapies, but there are other drugs that can do it as well.

When does cardio-toxicity manifest?

Cardio-toxicity does not always occur at the beginning when someone has commenced on systemic anti-cancer therapy. Patients who present very acutely within hours or days of commencing their therapy, although they tend to have a very dramatic presentation, ironically, they seem to have the best prognosis. Everything usually settles down with some treatment and is reversible.

It’s the patients who present months to years after having their treatment, who can be most challenging. This is why it’s so important to take a proper medical history for all patients and think outside the box.

Keep an open mind and remember that cardio-toxicity has lots of manifestations but also has a very variable timescale. If you’ve got a patient with any of these cardiovascular problems, always think: are they a cancer patient? Have they had treatment? When was the treatment?

Demand for collaborative cardio-oncology services is only going to go in one direction and it’s not just for cardio-oncologists, either. All clinical cardiologists are going to see patients with cancer in their clinics, whether that’s valve clinics, percutaneous coronary intervention clinics, heart rhythm clinics or hypertension clinics, because, as I’ve said, cardio-toxicity is much broader than left ventricular systolic dysfunction.

How do you classify high-risk patients before chemotherapy, and do these patients still receive this treatment?

ESC’s position paper on baseline cardiovascular risk assessment in cancer patients from a few years ago is a really useful document.

If we can identify patients at high risk of cardio-toxicity from the beginning, we can optimise things as much as possible. It’s really important that we work with the oncologist to persuade them to take a blood pressure, to do an ECG and to take a history at the beginning of cancer therapy so that we can focus our energies and resources on those that probably need us most.

The ESC guideline published in 2022 comes with a risk calculator. You can download the app onto your phone, and then you put in the patient’s variables: age, troponin, previous history, whatever it might be. Then it will tell you whether they’re low, medium, high or very high risk.

In terms of what that means for their cancer therapy, we will sometimes make a decision with the oncologist and the patient that their risk is too high to proceed with cancer therapy. These are usually patients who are not due to receive curative chemo. If the chemotherapy makes the difference between life and death and is potentially lifesaving then it would be unusual for us to say we can’t give it.

Usually, we will do everything in our power to enable the oncologist to give what they need. But there are certain circumstances where that wouldn’t be the case. For example, I’d be very reluctant for patients who’ve had coronary artery spasm with cardiac arrest to have more of the same chemo because we know that the risk of recurrence is significant. But that would be quite extreme and, as I say, we would work hard to enable the chemo or other treatment to continue.

Sometimes there might be two different treatment options with different risks and benefits. We’ll always bring the patient into that conversation and say, ‘look, we’ve got two different options from a cancer point of view, one is associated with a risk to your heart, the other isn’t’, and we’ll talk a bit about the risk and benefit from the cancer and cardiology sided, and then make that decision together.  

Nobody should be making unilateral decisions about these patients; it should be a real collaborative, multidisciplinary approach.

The spring 2024 Clinical Excellence in Cardiovascular Care event will take place on 19 March, with Dr Rebecca Dobson as chair. Registrations for all members of the multidisciplinary team are now open.

Type 2 diabetes remission associated with reduction of CVD and CKD complications, study finds

16th February 2024

Patients who successfully reversed a type 2 diabetes diagnosis though lifestyle changes substantially reduced their cardiovascular disease (CVD) and chronic kidney disease (CKD) risk in the long term, a study has found.

Published in the journal Diabetologia, the results came from a large trial of almost 4,500 participants in which doctors were comparing an intensive lifestyle programme with standard diabetes education and support.

Taking no diabetes medications and having a HbA1c of less than 48 mmol/mol (6.5%) at a single point in time was classed as remission.

Overall, those who achieved remission through the lifestyle changes – in whichever group – had a 33% lower rate of CKD and a 40% lower rate of CVD.

But those who had the most intensive support were more likely to be in remission from their diabetes, with 12% meeting the criteria at least one follow-up and falling to 7% over time compared with around 2% in the regular support group.

Being in remission overall was significantly linked to changes in weight and risk factors over the years, the study found.

Average weight loss associated with remission was 7.3kg after one year and 4.5kg after four years.

There were also significantly greater improvements in HDL-cholesterol and fitness after one and four years, and significantly greater systolic blood pressure improvements after one year among participants with remission compared with those without remission, the team said.

The analysis also showed systolic blood pressure decreased more and HDL-cholesterol increased more among participants who achieved a greater duration of diabetes remission.

There was a dose-response relationship with those who had remission for at least four visits seeing the most impact, the researchers said.

Those taking part in the study – which ran between 2001 and 2016 – had a mean age of 59 years and on average were in the range of severe obesity.

It was noted that while 18% of participants achieved remission at some point during follow-up, the percentage of participants with current remission had decreased to 3% by the eighth year of the study.

The figures underline, the challenges of keeping weight off using lifestyle interventions, the researchers said.

But for those with at least four years of remission the risk of CKD and CVD was reduced by 55% and 49% respectively.

The analysis also noted participants with a short duration of diabetes, low starting HbA1c and a large magnitude of weight loss were most likely to experience remission.

Study lead Professor Edward Gregg, head of the School of Population Health, RCSI University of Medicine and Health Sciences in Dublin, said: ‘As the first intervention study to associate remission with reduction of diabetes-related complications, this is encouraging news for those who can achieve remission from type 2 diabetes.

‘While our study is also a reminder that maintenance of weight loss and remission is difficult, our findings suggests any success with remission is associated with later health benefits.’

Another recent study has found that regular bouts of moderate to vigorous physical activity can protect patients with type 2 diabetes from developing kidney disease.

A version of this article was originally published by our sister publication Pulse.

Do JAK inhibitors increase the risk of MACE in atopic eczema?

17th August 2023

JAK inhibitors are known to increase the risk of major adverse cardiovascular events when used in rheumatoid arthritis, but does this elevated risk also apply when this class of drugs is used in atopic eczema? Clinical writer Rod Tucker investigates.

Since the 1990s, the treatment of severe rheumatoid arthritis (RA) has centred on biologics such as tumour necrosis factor (TNF) inhibitors. However, a better understanding of cell signalling pathways and, in particular, intracellular signal transduction, led to the development of alternative therapies, one of which being oral Janus kinase (JAK) inhibitors. Several of these have been approved for use in RA since 2011.

What’s more, as JAK inhibitors disrupt intracellular signalling through a variety of cytokine and haematopoietic growth factor receptors, this mode of action suggests the drug class may have a much wider role in a number of immune-mediated inflammatory diseases. As such, approvals for JAK inhibitors in Crohn‘s disease, psoriasis and atopic eczema have been seen in recent years.

JAK inhibitors and MACE in context

Despite their apparent effectiveness in RA, a recent post-marketing study has raised safety concerns over JAK inhibitors compared to TNF inhibitors. The Oral Rheumatoid Arthritis Trial (ORAL) was a randomised, post-authorisation, non-inferiority trial designed to evaluate the safety and efficacy of the JAK inhibitor tofacitinib compared to a TNF inhibitor such as etanercept or adalimumab. It focused on patients with RA who were aged 50 or older and had at least one additional cardiovascular risk factor.

The findings were somewhat disturbing. JAK inhibitor use led to a significantly higher incidence of both major adverse cardiovascular events (MACE) and cancers compared to a TNF inhibitor, even though the efficacies were broadly similar.

The ORAL trial served to highlight how JAK inhibitors may increase the risk of MACE when used in patients with RA who are already at an elevated risk due to their condition. Indeed, a meta-analysis of 24 studies with over 111,000 RA patients estimated a 50% higher risk of cardiovascular mortality.

So, with three JAK inhibitors (upadacitinib, baricitinib and abrocitinib) approved for atopic eczema, and representing an important and promising development for its treatment, should dermatologists be concerned over the risk of MACE when using this class of drugs?

Atopic eczema and the risk of MACE

Before considering whether JAK inhibitors might increase the risk of adverse cardiovascular sequelae in those with atopic eczema, its worth exploring whether atopic eczema, itself an inflammatory condition, is linked to a higher risk of MACE. After all, such a risk is theoretically possible, given the emerging evidence of the pivotal role of inflammation in the development and progression of both cardiac and vascular diseases.

The current evidence of an association between atopic eczema and MACE is equivocal. Some work, for instance, clearly demonstrates that atopic eczema is associated with increased risk of myocardial infarction compared to the general population. In contrast, another study found no such independent association in women.

Nevertheless, pooling data from several studies does suggest a positive relationship. For example, a 2018 meta-analysis of 15 studies, which included over 3.5 million participants, did show that atopic eczema was independently associated with an increased risk of stroke and myocardial infarction, especially in male subjects and those with more severe disease.

In addition, a recent Danish study, looked at what happened to patients over time following a diagnosis of atopic eczema. It included over 40,000 atopic eczema patients and an equal number of matched controls and found that adults were at a significantly higher risk of experiencing a subsequent cardiovascular disease.

Finally, a UK prospective study including 387,439 patients with atopic eczema followed for over five years, concluded that severe active atopic eczema was associated with an increased risk of cardiovascular outcomes.

While prospective studies are subject to confounding, Mendelian randomisation studies, are able to provide an estimate causality without the influence of confounders. One such study showed that asthma and atopic eczema were causal risk factors for heart failure and suggested that the underlying inflammatory nature of both diseases was a major contributory factor.

As ever, things are never that straightforward. In a recent bidirectional Mendelian randomisation study, it was found that there was no robust association between cardiovascular disease and atopic eczema.

JAK inhibitors and MACE in atopic eczema

In trying to establish if there was a higher risk of MACE in patients with atopic eczema prescribed a JAK inhibitor, researchers recently undertook a systematic review and meta-analysis. The findings were published in July 2023 in the British Journal of Dermatology and included phase 2b or 3 randomised controlled trials and controlled cohort studies.

The primary outcome was the occurrence of MACE, which the researchers defined as a composite of acute coronary syndrome (ACS), ischaemic stroke and CV death.

A total of 23 studies were included in the analysis. Very few cases of MACE were found, leading the researchers to suggest that JAK inhibitors may have little-to-no effect on the occurrence of MACE in patients with atopic eczema compared to placebo. However, they did add the caveat that the evidence was uncertain.

In addition, MACE generally occurred in patients at a high cardiovascular risk and not in the younger, healthy patients typically seen in routine clinical practice.

Further and reassuring evidence of the absence of a possible association with MACE comes from real-world studies on the use of JAK inhibitors in atopic eczema. There have been at least four such studies, none of which have identified any cases of MACE, even though some have been conducted in patients with more severe disease.

EMA safety advice

Although patients with atopic eczema may have a higher risk of MACE, this is more likely to occur either in those with severe disease or for patients at a greater risk of cardiovascular disease. Over time, pharmacovigilance data will no doubt shed further light on the level of risk associated with JAK inhibitors.

For now, the European Medicines Agency (EMA) issued advice in January 2023 on the use of JAK inhibitors in all chronic inflammatory disorders, including atopic eczema. This recommended avoiding against the use of a JAK inhibitor in those aged 65 years or above, in patients at an increased risk of major cardiovascular problems, smokers and individuals at a higher risk of cancer, unless there are no suitable alternatives.

For most patients with atopic eczema, JAK inhibitors represent a potentially game-changing addition to a dermatologist’s armamentarium for their treatment. Provided that clinicians heed the current safety guidance, those prescribed a JAK inhibitor for atopic eczema have much to gain but without the attendant risk of MACE.

Higher CVD risk in patients with obstructive sleep apnoea taking beta-blockers

16th August 2023

The use of beta-blockers is associated with an increased risk of cardiovascular disease (CVD) and a trend for a higher mortality risk among patients with obstructive sleep apnoea (OSA), according to the findings from a recent study.

Researchers from University College London School of Pharmacy found that the use of beta-blocker drugs in patients with OSA increases the five-year risk of mortality and adverse cardiovascular outcomes.

In the absence of real-world evidence, the study, published in The Lancet Regional Health – Europe, investigated the impact of beta-blocker use on all-cause mortality and adverse cardiovascular outcomes in patients with OSA.

For the purposes of their analysis, the researchers turned to IQVIA Medical Research Data – a nationwide database of primary care records in the UK that contains around 6% of the total UK population in 2015. The database includes demographic and lifestyle information such as smoking and alcohol consumption, medical diagnoses and procedures, together with prescribing information.

Included patients were adults aged over 18 who had a diagnosis of OSA in their medical records. The team then compared the treatment strategies of initiating oral beta-blockers versus not starting a beta-blocker in these patients.

The outcomes of interest were all-cause mortality or a diagnosis of CVD, defined as a composite event of angina, myocardial infarction, stroke/transient ischaemic attack, heart failure or atrial fibrillation.

Beta-blocker usage in patients with OSA

A total of 37,581 patients met the eligibility criteria and were followed for a median of 4.1 years.

The five-year absolute risk of all-cause mortality and CVD outcomes were 4.9% and 13.0% among beta-blocker users, compared to 4.0% and 9.4% among non-beta-blocker users, respectively.

Commenting on these findings, study lead Dr Kenneth Man said: ‘Our study underscores the urgent need for further investigation into the relationship between beta-blockers and health outcomes in OSA patients.

‘Our hope is that this information will help medical professionals make more informed decisions when treating patients with OSA.‘

This extensive study is one of the few exploring the real-world implications of medical treatment in OSA patients. It emphasises the importance of careful and continued monitoring of these patients and encourages further investigation in this field.

Further studies are anticipated to confirm these findings and delve deeper into understanding the association between beta-blocker usage and patient outcomes. Until such studies are conducted, the medical community is urged to consider the potential risks highlighted by this research when treating patients with OSA.

Successful psychological therapy for depression may reduce subsequent CVD risk

25th April 2023

Psychological therapy that improves a patient’s depression could also reduce their risk of developing cardiovascular diseases in the future, according to new research.

In the first-of-its-kind study, published in the European Heart Journal, researchers retrospectively examined a cohort of 636,955 individuals who had completed the Improving Access to Psychological Therapy (IAPT) primary care programme for depression.

Individuals were free of cardiovascular disease (CVD) before entry into the IAPT and over 45 years of age, with a mean age of 55. Some 58.6% showed an improvement in their depression. Regression models then estimated the association between improvement of depression and the risk of subsequent CVD events.

In fully adjusted models, those whose depression symptoms improved after psychological therapy were 12% less likely to experience a cardiovascular event than those who did not, over an average three-year follow up.

Indeed, improving depression symptoms gave rise to a significant lowering in the risk of any new onset of CVD (hazard ratio, HR = 0.88, 95% CI 0.86 – 0.89). This was true for coronary heart disease (HR = 0.89), stroke (HR = 0.88) and all-cause mortality (HR = 0.81).

This reduction in CVD risk and risk of death from all causes was higher in those aged under 60, with 15% and 22% decreased risk respectively. Those over 60 years of age had a 5% decreased risk of developing CVD and 14% decreased risk of death from all other causes.

The authors suggest that management of depression with psychological therapies might therefore reduce the risk of subsequent CVD, but more research is needed to understand the causality of these associations.

Long-term physical health benefits

Commenting on the study, lead author Celine El Baou, PhD candidate from UCL Psychology & Language Sciences, said: “The findings are important as they suggest that the benefits of psychological therapy may extend beyond mental health outcomes and to long-term physical health. They stress the importance of increasing access to psychological therapy to under-represented groups, for example minority ethnic groups who may be more at risk of experiencing cardiovascular disease.”

The authors also noted that previous studies have shown that people who experience depression are around 72% more likely to develop cardiovascular disease in their lifetime.

A study published earlier in 2023 also highlighted that depression and poor mental health among young adults is more likely to lead to premature CVD and suboptimal cardiovascular health. The researchers concluded that prioritising mental health might help to reduce CVD risk and improve cardiovascular health in young adults.

In 2021/22, 1.24 million referrals accessed the Improving Access to Psychological Therapies (IAPT) programme (now renamed NHS Talking Therapies for anxiety and depression) compared to 1.02 million the previous year, according to latest NHS Digital statistics.

Pregnancy hypertensive disorders linked to higher future risk of cardiovascular disease

24th February 2023

Pregnancy hypertensive disorders increase the longer term risk of cardiovascular diseases according to a results of a Mendelian analysis

Women who experience pregnancy hypertensive disorders such as preeclampsia have a higher risk of developing cardiovascular disorders in the future according to the findings of a Mendelian randomisation analysis by UK and Dutch researchers.

Hypertensive disorders during pregnancy affect 8% to 10% of all pregnant women and can lead to serious complications including mortality. In fact, one systematic analysis revealed how 14% of maternal deaths were due to hypertensive disorders. Moreover, observational evidence suggests that having a pregnancy-related hypertensive disorder increases the risk of cardiovascular events in later life. Nevertheless, observational data cannot be used to determine a causal relationship due to potential confounding. However, a better study design that can determine whether such a relationship is causal is the use of Mendelian randomisation (MR). This approach uses the genetic risk of disease as a proxy for the disease itself and can be used to mitigate the effect of confounding, as the MR estimate can be used to interpret the effect of the exposure, in this case pregnancy-related hypertensive diseases, on the outcome of interest (cardiovascular disease).

In the current study, researchers used estimates of genetic association obtained from genome-wide association data, to examine the association between gestational hypertension and preeclampsia and the risk of subsequently developing coronary artery disease, ischaemic stroke, heart failure and atrial fibrillation. The team also employed mediation analysis based on multivariable MR, to consider the impact of potential mediators e.g., body mass index, systolic blood pressure etc, on any identified associations.

Pregnancy hypertensive disorders and future cardiovascular risk

For any genetically predicted hypertensive disorder, there was an elevated risk of developing coronary artery disease (Odds ratio, OR = 1.24, 95% CI 1.08 – 1.43, p = 0.02). The risk was also elevated when considering gestational hypertension (OR = 1.08, p = 0.04), preeclampsia or eclampsia (OR = 1.06, p = 0.03) and ischaemic stroke (OR = 1.27, P < 0.001). However, the risks were non-significant for both gestational hypertension and preeclampsia and there were also non-significant for both heart failure and atrial fibrillation.

In the mediation analysis, there was a partial attenuation of the overall risk for CAD after adjusting for systolic blood pressure (adjusted OR = 1.10 vs 1.24) and the presence of type 2 diabetes (adjusted OR = 1.16 vs 1.24).

The authors concluded that given their findings, the presence of pregnancy-related hypertensive disorders should be considered as risk factors for cardiovascular disease.

Rayes B et al. Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. JAMA Netw Open. 2023

Depression and poor mental health linked to higher incidence of CVD in young adults

3rd February 2023

Both depression and poor mental health days in young adults are associated with a higher risk of premature cardiovascular disease

Depression and poor mental health among young adults is more likely to lead to premature cardiovascular disease (CVD) and suboptimal cardiovascular health according to the findings of a large study of US adults by US and UK researchers.

A worrying trend over the past 20 years is the observed increase in the prevalence of recognised cardiovascular disease risk factors e.g., obesity, physical inactivity and a poor diet, among younger individuals in developed countries. Moreover, though not considered as a traditional CVD risk factor, the American Heart Association accepts that depression should be considered as a risk factor for adverse outcomes in patients with acute coronary syndrome. But to what extent does the presence of depression or even poor mental health, affect the risk of CVD among younger adults was the subject of the current study.

Researchers used data from the behavioural risk factor surveillance system which includes a nationally representative sample of non-institutionalised adults. The system assesses health-related risk behaviours and chronic health conditions, based on an annual telephone survey. The research team collected data on self-reported depression and poor mental health days (PMHDs), as well as CVD and suboptimal cardiovascular (CV) health, based on recognised risk factors, e.g., smoking, physical inactivity. In addition, self-reported PMHDs were categorised as 0, 1 – 13 or 14 to 30.

Depression and risk of premature cardiovascular disease
In total, data were collected from 593,616 with a mean age of 34.7 years (50.3% male).

The prevalence of depression was 19.6% and 2.5% for CVD. The researchers calculated that those with depression had a much higher odds of CVD compared to those without the condition (odds ratio, OR = 2.32, 95% CI 2.13 – 2.51). There was also a graded increased risk of CVD, depending on the number of reported PMHDs rising from an odds ratio of 1.48 (1 to 13 days) to 2.29 (14 to 30 days). These estimates were unaffected by gender or individual’s status (rural or urban). Suboptimal cardiovascular health was also higher among those with depression (OR = 1.79) and a similar graded relationship observed based on the number of PMHDs.

The authors concluded that based on their findings, prioritising mental health might help to reduce CVD risk and improve cardiovascular health in young adults.

Kwapong YA et al. Association of Depression and Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young Adults in the United States. J Am Heart Assoc 2023

Morning physical activity linked to lowest risk of cardiovascular disease

8th December 2022

Morning physical activity is associated with the greatest risk reduction for cardiovascular disease and stroke compared to a midday pattern

Individuals with higher levels of morning physical activity have the lowest risk of incident cardiovascular disease and stroke compared to those who have a midday peak pattern according to an analysis by Dutch researchers.

Cardiovascular diseases (CVD) are the leading cause of global mortality with an estimated 17.9 million lives lost each year. One modifiable factor linked to CVD is physical activity (PA) and data suggests that PA is not only associated with lower risk for of CVD but that the greatest benefit is seen for those who engage in higher levels of activity. However, emerging evidence suggests that the timing of PA may also be an important and influential factor. For example, in a study of more than 7,000 women, researchers found that women who are less active during morning hours may be at higher risk of obesity. In addition, an exercise-based trial which considered the impact of exercise timing on weight loss, showed that morning physical activity led to a significantly higher weight loss compared to evening activity. But mornings might not always be best as a study in men with type 2 diabetes observed that those who undertook high intensity interval training (HIIT) in an afternoon compared to morning session, had better glucose control.

In trying to better understand the impact of the timing of physical activity on the risk of incident CVD, the Dutch researchers collected physical activity data from participants in the UK-Biobank through triaxial accelerometer over a 7-day period which collected 24-hour mean activity levels. The team then used this data to create four different clusters of physical activity: cluster 1 represented the average pattern among the total biobank population which peaked around midday; cluster 2 were those with an early morning peak; cluster 3 a late morning peak and cluster 4, those with an evening peak. Regression analysis was used based on two models, the first (model 1) was adjusted for age and gender, and the second (model 2) additionally adjusted for body mass index and smoking status.

Morning physical activity and cardiovascular outcomes

A total of 86,657 individuals with a mean age of 61.6 years (58% female) were included and followed for 6 years during which time there were 2,911 cases of incident CVD and 796 strokes.

In an analysis based on model 1, participants who had higher levels of morning or later morning (clusters 2 and 3) physical activity, had a 11% (hazard ratio, HR = 0.89, 95% CI 0.80 – 0.99) and 16% (HR = 0.84, 95% CI 0.77 – 0.92) respectively, lower incidence of incident CVD compared to those in cluster 1. However, only those in cluster 3 (late morning physical activity) had a significantly reduced risk of stroke (HR = 0.83, 95% CI 0.70 – 0.98) and ischaemic stroke (HR = 0.79, 95% CI 0.64 – 0.97). Interestingly, when the researchers used model 2, the benefits were no longer statistically significant apart from a reduced risk of ischaemic stroke for those in cluster 3 (HR = 0.73, 95% CI 0.57 – 0.94).

In subgroup analysis based on gender and using model 2, there were statistically significant reductions in the risk of incident CVD but only among women who were either early and later morning exercisers. In addition, the risk of ischaemic stroke was only significantly lower among women in cluster 3 (HR = 0.56, 95% CI 0.38 – 0.83). When stratifying by participant levels of activity (i.e., either less or more active) and using model 2, although there were reductions in the risk of both CVD and stroke, among those who were more active, these reductions were non-significant.

The authors concluded that morning physical activity was associated with lower risks of incident cardiovascular diseases and that these findings highlighted the potential importance of chrono-activity in CVD prevention.

Albalak G et al. Setting your clock: associations between timing of objective physical activity and cardiovascular disease risk in the general population. Eur J Prev Cardiol 2022