Category: Cardiovascular Disease

Categories : Cardiovascular Disease Exercise GenderTags :

Strenuous Jobs Increase Men’s Cardiovascular Risk, but Reduce Women’s

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Photo by K. Mitch Hodge on Unsplash

A long-term Danish study found that high physical activity at work was associated with higher risk of ischaemic heart disease (IHD) in men, but in women, this was associated with lower risk. The findings, published in the European Journal of Preventive Cardiology, highlight the importance of taking gender into account when considering the impact of high levels of occupational physical activity (OPA).

While previous studies have shown that physical activities in leisure time are protective against cardiovascular disease, high levels of OPA were shown to have no benefit – or even a detrimental effect.

The study followed up participants aged 30–61 years old after 34 years who took part in the Danish Monica 1 study in 1982–84. Participants, 1399 women and 1706 men, were actively employed, without prior IHD and who answered a question on OPA. The participants’ medical records were located in the Danish National Patient Registry and the researchers analysed the data, controlling for increasing numbers of factors such as age, then age and sex, and then age and sex plus factors such as smoking.

Compared to women doing sedentary work, women in all other OPA categories had a lower hazard ratio (HR) for IHD. Among men, the risk of IHD was 22% higher among those with light OPA, and 42% and 46% higher among those with moderate OPA with some lifting or strenuous work with heavy lifting, respectively, compared to men with sedentary OPA. Compared to women with sedentary work, HR for IHD was higher among men in all OPA categories, and a statistically significant interaction between OPA and sex was found.

Demanding or strenuous OPA seems to be a risk factor for IHD among men, whereas a higher level of OPA seems to protect from IHD among women. The researchers wrote that this underlines the importance of taking into account sex differences in studies of health effects of OPA. Future studies should investigate the underlying mechanisms for this difference, such as differences in exposure and physiology.

Categories : Cardiovascular DiseaseTags :

Getting Under 5 Hours’ Sleep Increases Risk of Peripheral Artery Disease

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Sleeping man
Photo by Mert Kahveci on Unsplash

Compared with seven to eight hours, sleeping less than five hours a night is associated with a 74% raised likelihood of developing peripheral artery disease (PAD) according to a study published in the European Heart Journal – Open.

“Our study suggests that sleeping for seven to eight hours a night is a good habit for lowering the risk of PAD,” said study author Dr Shuai Yuan of the Karolinska Institute.

A Lancet study showed that more than 200 million people globally have peripheral artery disease (PAD), where arteries in the legs are clogged, restricting blood flow and increasing the risk of stroke and heart attack.

Dr Yuan said: “Insufficient night-time sleep and daytime napping have previously been associated with a raised risk of coronary artery disease which, like PAD, is caused by clogged arteries. In addition, sleeping problems are among the top ranked complaints in PAD patients. There are limited data on the impact of sleep habits on PAD and vice versa, and our study aimed to fill that gap.”

The two-part study included more than 650 000 participants. First, the researchers analysed the associations of sleep duration and daytime napping with the risk of PAD. In the second part, the investigators used genetic data to perform naturally randomised controlled trials – called Mendelian randomisation – to examine causality of the associations.

Dr Yuan said: “Observational analyses are limited by reverse causality – meaning that if an association between sleep habits and PAD is found, we cannot be certain if sleep habits caused PAD or having PAD caused the sleep habits. Mendelian randomisation is a robust method for evaluating causality and provides more certainty about the results.”

Taken together, the strongest evidence was for short sleep, where the relationship with PAD went both ways. In an observational analysis of 53 416 adults, sleeping less than five hours a night was associated with a nearly doubled risk of PAD compared with seven to eight hours (hazard ratio [HR] 1.74). This finding was supported by further analyses in 156 582 and 452 028 individuals. In the causal studies, short sleep was associated with an increased risk of PAD and, in addition, PAD was associated with an increased likelihood of short sleep. Dr Yuan said: “The results indicate that brief night-time sleep can raise the chance of developing PAD, and that having PAD increases the risk of getting insufficient sleep.”

Regarding long sleep, in an observational analysis of 53 416 adults, sleeping eight hours or more per night was linked with a 24% higher risk of PAD compared with seven to eight hours (HR 1.24). This finding was supported by analyses in two larger populations of 156 582 and 452,028 individuals. However, no causal relationships were found between long sleep and PAD. Similar results were reported for napping, where daytime nappers had a 32% higher risk of PAD compared to those who did not nap (HR 1.32) but no causal links were found. “More studies are needed on the relationships between lengthy night-time sleep, daytime napping and PAD,” said Dr Yuan. “Although we found associations in the observational studies, we could not confirm causality.”

He concluded: “More research is needed on how to interrupt the bidirectional link between short sleep and PAD. Lifestyle changes that help people get more sleep, such as being physically active, may lower the risk of developing PAD. For patients with PAD, optimising pain management could enable them to have a good night’s sleep.” 

Source: European Society of Cardiology

Categories : Cardiovascular DiseaseTags :

Hunger Hormone Increases Cardiac Function in Heart Failure

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Source: Pixabay CC0

A clinical study published in the European Heart Journal shows that the hunger hormone ghrelin can increase the heart’s pump capacity in patients with heart failure.

Heart failure occurs when the heart muscles are weakened, such as from myocardial infarction, reducing the ability to pump blood. Current treatments can slow disease progression, but none directly increase the heart’s pumping capacity.

Ghrelin is an endogenous hormone that has many receptors distributed in cardiac muscle tissues. It increases the appetite and stimulates the release of growth hormones. The researchers believe that its receptors are a promising target for enhancing the heart’s pumping capacity.

“Heart failure is the most common cause of hospitalisation in older generations and is associated with a poor quality of life and high mortality,” says principal investigator Lars Lund, professor at the Department of Medicine, Solna, Karolinska Institutet, and senior consultant at Karolinska University Hospital. “If we can find ways to increase the heart’s pump function, we can potentially improve life quality and prognosis for these patients.”

In this double-blind study, 30 patients with heart failure at Karolinska University Hospital’s cardiology unit were randomly assigned to two groups, receiving either active treatment with ghrelin or a placebo given intravenously for two hours. The participants were followed up after two to five days.

Pump function up by 28%

After two hours’ treatment, the cardiac output had increased by an average of 28% in the ghrelin group, (4.08 ± 1.15 to 5.23 ± 1.98 L/min) compared to a small reduction in the placebo group (4.26 ± 1.23 to 4.11 ± 1.99 L/min). The increase was from more blood being pumped per beat, as the heart rate remained unchanged or was even slightly slower. At the two- to five-day follow-up, the pump capacity was still 10% higher in the ghrelin group compared to in the placebo group.

No serious adverse reactions were seen, though the ghrelin group had slightly elevated levels of a heart-failure biomarker, which would need to be investigated further. The small size of the group makes limits the generalisability of the results.

Using mouse heart cells, the researchers observed that treatment with ghrelin increased the contractile function of the heart cells, and they identified a novel molecular mechanism for this increase. The researchers now plan to do larger clinical studies.

Source: Karolinska Institutet

Categories : Cardiovascular Disease Neurodegenerative DiseasesTags :

Atrial Fibrillation Linked to Dementia Risk

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Source: American Heart Association

A large representative study found that individuals with newly diagnosed atrial fibrillation had a modestly elevated risk of developing dementia. The Journal of the American Heart Association study found that this risk was higher in younger adults and those without chronic kidney disease, but did not substantially vary across sex, race, or ethnicity.

In this study of nearly 200 000 adults, incidence rates for dementia over a median follow-up of 3.3 years were 2.79 versus 2.04 per 100 person-years in individuals with versus without atrial fibrillation, respectively. (This means that over one year, there would be an average of 2.79 dementia diagnoses among 100 people with atrial fibrillation and 2.04 diagnoses among 100 people without atrial fibrillation. This translates to 279 per 10 000 and 204 per 10 000.)

After adjustments, atrial fibrillation was associated with a 13% higher risk of dementia. Adults aged <65 years had a 65% higher risk compared with older adults, those without chronic kidney disease had a 14% higher risk than those with chronic kidney disease.

“These data highlight a possible link between atrial fibrillation and risk of subsequent dementia in certain populations. Further studies are needed to understand the mechanisms to explain this association, which may inform the use of treatments for atrial fibrillation,” said corresponding author Nisha Bansal, MD, MAS, of the University of Washington School of Medicine.

Source: Wiley

Categories : Cardiovascular Disease Surgeries & ProceduresTags :

Smaller Bioprosthetic Aortic Valves Safer than Previously Believed

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Researchers in Sweden have performed a nation-wide study of patients who underwent bioprosthetic aortic valve replacement between 2003 and 2018. The study, published in the Journal of the American College of Cardiology, shows that it is less dangerous than previously believed to receive a small bioprosthetic aortic valve in relation to the patients size.

During surgical aortic valve replacement, the patient receives a valve prosthesis that matches the size of the aortic root. Sometimes, that size is too small in relation to the patient’s body size. This puts strain on the heart to pump enough blood that the body needs through a narrow valve. The level of “narrowness” is measured as Prosthesis Patient Mismatch, PPM.

“Prior studies have shown that both moderate and severe PPM decreases survival and increases the risk for heart failure. In our study, we can confirm that severe PPM decreases survival and increases the risk for heart failure, while moderate PPM has a very limited effect on survival and no effect on the risk for heart failure”, says Michael Dismorr, postdoctoral researcher at the Department of Molecular Medicine and Surgery and first author of the study.

The study

The study included all patients who underwent bioprosthetic aortic valve replacement in Sweden between 2003 and 2018. Patients were identified from the Swedish cardiac surgery register, part of the SWEDEHEART register. The database was enriched with data from other national health data registers. By using the statistical method regression standardization we were able to estimate the risk for the outcomes death, heart failure and reintervention in absolute terms between the groups no, moderate and severe PPM.

The study shows that the estimated risk difference between no and moderate PPM for death after 10 years of follow-up was -1.7% (-3.3% to -0.1%) compared to -4.6% (-8.5% to -0.7%) for severe PPM.

The risk difference for heart failure after 10 years of follow-up was -1.1% (-2.5% to 0.2%) between patients with no and moderate PPM.

“A risk difference of a single percent after 10 years of follow-up cannot be said to be of clinical significance, even if it is statistically so. However, it is important to note that these are hard clinical outcomes. We did not have access to “soft” outcomes such as quality of life, which might be decreased in patients with moderate PPM, and in that case of course of great importance to those patients”, says Michael Dismorr.

Next steps

“Now we want to study the effect of PPM in patients who underwent transcatheter aortic valve replacement, a so called TAVR procedure. This is important knowledge when deciding which patients will benefit the most from a surgical replacement, and which patients will benefit the most from a transcatheter replacement”, says Michael Dismorr.

Source: Karolinska Institutet

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

Novel Antihypertensive Flounders in Early Trial Phase

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Blood pressure cuff
BP cuff for home monitoring, Source: Pixabay

A phase II trial with the novel antihypertensive baxdrostat did not replicate the impressive results in a similar trial for the drug in treatment-resistant hypertension, failing to improve on placebo effect.

Deepak Bhatt, MD, MPH, of Mount Sinai Heart in New York City, presented the disappointing findings at the American College of Cardiology (ACC) annual meeting, but noted that the findings were not a complete write-off for the drug, hampered as the trial was by poor patient adherence and the confounding effect of other antihypertensives.

For baxdrostat, seated systolic blood pressure was lowered by 16.0–19.8mmHg across the doses tested, compared to 16.6mmHg for placebo, a nonsignificant difference. Diastolic blood pressure drops showed a similar pattern, even slightly favouring placebo.

HALO included 249 participants with a mean seated systolic blood pressure of 140–180 mmHg at baseline despite treatment with a stable regimen of an ACE inhibitor or one of those drugs plus a thiazide diuretic or a calcium channel blocker. They were randomised to placebo or a 0.5-, 1.0-, or 2.0-mg dose of baxdrostat for 8 weeks.

In the prior phase II BrighHTN trial, baxdrostat reduced systolic blood pressure by 11 and 8.1 mm Hg more than placebo in the two higher dose groups.

The drug, which is in a new class of highly selective aldosterone synthase inhibitors, did decrease serum aldosterone and increase plasma renin activity as expected compared with placebo in HALO.

A post hoc analysis to understand why the trial failed despite high pill-count based adherence showed that 36% of the baxdrostat patients in the highest, 2-mg dose group (20 of 54) were actually not adherent, based on plasma levels < 1% of expected.

ACC session moderator Kim Eagle, MD, of the University of Michigan in Ann Arbor wondered if the patients were flushing their pills, and Bhatt replied that these were clustered at a few sites, highlighting issues of site selection and providing patient support.

The adherence problem does not explain away the placebo effect, Eagle told MedPage Today. “The placebo effect may well be that by enrolling in a trial, the patient is also taking their other meds for hypertension. Recall that the patients were already supposed to be taking several antihypertensives.”

Nevertheless, he called it compelling that, in “patients who were taking the larger dose and who had evidence of adherence by blood levels, the drug clearly seems to work.”

Source: MedPage Today

Categories : Cardiovascular Disease Environmental EffectsTags :

Thesis Finds ‘Forever Chemicals’ don’t Increase Cardiovascular Disease Risk

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A new thesis by Karolinska Institutet student Tessa Schillemans has found that exposure persistent environmental pollutants did not increase biomarkers of cardiovascular disease risk – rather, exposure reduced them, raising further questions on their complex interactions with the environment and within the human body.

What is the thesis about?
The thesis is about a group of environmental pollutants called per- and polyfluoroalkyl substances (PFAS), also called “forever-chemicals”. Since we all are exposed and their chemical structure resembles that of fatty acids, we wanted to investigate whether exposure to PFAS associated with increased risk of cardiovascular disease. Additionally, we also explored if we could gain insight in potential underlying molecular pathways by linking PFAS exposure to biological molecules in the blood.

Can you tell us about some interesting results?
We found no evidence that PFAS was linked to increased risk of cardiovascular disease in the general population. If anything, rather the opposite – which also deserves careful consideration. We did observe associations with higher cholesterol, lower triglycerides and with lipid metabolism intermediates, which all point towards potential perturbations in lipid metabolism. 

What further research is needed in the area?
It is essential to fully understand any adverse consequences that PFAS may have, since they are omnipresent and persistent. Thus, epidemiological studies involving other outcomes and vulnerable subgroups (such as pregnant women and children) should also be performed, as disturbances in lipid metabolism could impact other physiological processes. For a deeper mechanistic understanding, integration of data from different biological systems (genome, epigenome, transcriptome, proteome, metabolome) in human and experimental settings would be optimal. Additionally, since humans are exposed to many different chemicals simultaneously and these could interact with each other, there is a need for studies that investigate multiple exposures at the same time (exposome studies).

Source: Karolinska Institutet

Categories : Cardiovascular Disease Medical Industry Metabolic DisordersTags :

Bempedoic Acid Could be a Viable Alternative to Statins

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Bempedoic acid, a new cholesterol-lowering drug, has the potential to be an effective substitute for patients who can’t tolerate statins. Bempedoic acid is an ATP citrate lyase inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events. Its effects on cardiovascular outcomes were uncertain, so researchers used a double-blind, randomised, placebo-controlled trial to determine outcomes on a variety of cardiovascular measures in statins-intolerant patients.

The study, published in the New England Journal of Medicine, recruited patients aged 18–85 years at increased cardiovascular risk and unable or unwilling to take statins due to adverse effects. Patients were first tested with placebo over a 4-week run-in period, and were not randomised if they experience unacceptable adverse effects or if adherence was less than 80%. The 13 970 patients who successfully completed run-in were randomised to receive bempedoic acid 180mg orally per day or matching placebo. 

The mean LDL cholesterol level at baseline was 139.0mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2mg/dL; the observed difference in the percent reductions was 21.1 percentage points in favour of bempedoic acid.

Compared to placebo, risk of fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause after significantly were lower by 13%, after a median of 40.6 months of follow-up. The risk of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction was 15% lower with bempedoic acid than with placebo, and the risks of fatal or nonfatal myocardial infarction and coronary revascularisation were 23% lower and 19% lower, respectively.

The researchers noted that the LDL-cholesterol lowering effects were similar in magnitude and predicted reduction in cardiovascular risks to that observed with statins. In addition, bempedoic acid did not increase glycated haemoglobin levels or the incidence of new-onset diabetes, unlike statins. Due to the demonstrated benefits, those taking placebo were offered the chance to transition to taking bempedoic acid.

A trial limitation was that it only included patients with statins intolerance, and who therefore had higher LDL cholesterol levels at baseline.

Categories : Cardiovascular DiseaseTags :

1 in 5 Patients at High Cardiovascular Risk Refuse Statins, Especially Women

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Heart disease is the leading cause of death worldwide, and statins are a vital medication against it – but they are notoriously unpopular, leading to poor adherence. Investigators from Brigham and Women’s Hospital conducted the first population-based study on patients’ nonacceptance of statin therapy recommendations, and published their results in JAMA Network Open.

The study found that in patients at high risk of developing cardiovascular disease, over 20% refused to take statin medications. They were particularly surprised to see that women were about 20% more likely than men to refuse statin therapy when it was first suggested by their physician, and 50% more likely than men to never accept the recommendation. The study also showed that all patients who refused statin therapy developed higher LDL cholesterol levels, likely increasing their risk even further.

“Our study highlights the alarming number of patients who refuse statins and signals that physicians must have discussions with patients about why,” says Alex Turchin, MD, MS, an associate professor at Harvard Medical School and director of quality in the Brigham’s Division of Endocrinology, Diabetes, and Hypertension. “We need to better understand what our patients’ preferences are and to be able to provide more patient-centered care.”

After Turchin began noticing that many of his patients with high cholesterol, including those with diabetes, were opting not to take safe and beneficial medications like statins that can lower cholesterol and bring down the risk of heart attack and stroke, he developed a system to more closely study the phenomenon by analysing the text of provider notes.

The study focused on high-risk patients who either had coronary artery or vascular disease, diabetes, very high cholesterol, or had suffered a stroke. All were recommended statin medications by their physicians to reduce their risk of heart attack and stroke and reduce cholesterol levels. The retrospective study included more than 24 000 patients who were seen at Mass General Brigham between January 1, 2000, and December 31, 2018.

“Even in this higher-risk patient population, so many people did not accept statin therapy,” Turchin said. The study found that while about two-thirds of the patients who were being recommended statin therapy eventually tried it, about one-third never did. And it took three times as long for people in the study who initially said no to taking statin medications to reduce their LDL cholesterol levels to less than 100, compared to people who initially said yes.

The study’s biggest surprise, however, was the much higher rate of refusal by women than men. Turchin and his colleagues wonder if this might be due in part to a false misconception that heart disease impacts men more than women, and plan to further research the reasons underlying these results.

“Ultimately, we need to talk to our patients and find out in more detail why they would prefer not to take statins,” Turchin says. He is currently looking at the impacts of nonacceptance of statin therapy on outcomes that matter to most to patients including heart attacks, strokes, and death. “I think people underestimate how much of a difference modern medicine has made in extending people’s lives, and their quality of life, and medications can play a big role in that.”

Source: Brigham and Women’s Hospital

Categories : Cardiovascular Disease GenderTags :

Gender Affirming Hormone Therapy Linked to Greatly Increased Cardiovascular Risk

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Source: CC0

People undergoing hormone replacement therapy (HRT) for gender dysphoria have a greatly increased risk of serious cardiac events, according to a study presented at the American College of Cardiology annual meeting. Compared to people with gender dysphoria not taking HRT, those taking HRTY saw a seven-fold risk increase for ischaemic stroke, and risk increases for myocardial infarction and pulmonary embolism.

People with gender dysphoria may use HRT as part of gender affirmation therapy to transition to a different gender than their biological sex at birth. HRT for this purpose is rapidly increasing, especially among teens and young adults.

Previous research on hormone-modulating medications has primarily focused on younger women using hormone-based birth control or on older women following a hysterectomy or during menopause. In these populations, long-term HRT has been associated with an increased risk of breast cancer, stroke and blood clots.

Researchers retrospectively examined rates of cardiovascular events in over 21 000 people with gender dysphoria from a national database of hospital records, of whom 1675 had used HRT. Typically, people assigned male at birth receive oestrogen and people assigned female at birth receive testosterone. Overall results found hormone replacements were associated with higher rates of cardiac events, mostly related to dangerous blood clots, but were not associated with higher rates of death.

Compared with hospitalised patients with gender dysphoria who had never used HRT, those taking gender affirmation HRT had higher rates for a range of in-hospital cardiovascular events:

  • ST-elevation myocardial infarction (OR 5.90, 95% CI 1.07-32.42)
  • Ischaemic cerebrovascular accident (OR 7.15, 95% CI 2.74-18.67)
  • Non-ST-elevation myocardial infarction (OR 3.30, 95% CI 1.20-9.04)
  • Pulmonary embolism (OR 4.92, 95% CI 2.08-11.62)

“It’s all about risks and benefits. Starting transitioning is a big part of a person’s life and helping them feel more themselves, but hormone replacement therapy also has a lot of side effects – it’s not a risk-free endeavour,” said Ibrahim Ahmed, MD, a third-year resident at Mercy Catholic Medical Center in Darby, Pennsylvania and the study’s lead author.

HRT was not associated with any increase in deaths, incident atrial fibrillation, diabetes, hypertension, haemorrhagic stroke, or heart failure.

Both oestrogen and testosterone are known to increase the clotting activity of blood, which could explain the increase in clotting-related cardiovascular events, researchers said. Those taking hormone replacement therapy also had higher rates of substance use disorder and hypothyroidism.

“Looking at a person’s medical and family history should definitely be part of the screening protocol before they even start hormone replacement therapy,” Ahmed said. “It is also important that people considering this therapy are made aware of all the risks.”

One limitation of the study is that it only accounted for whether individuals had ever used any type of hormone replacement therapy. To better inform clinical decisions, researchers said it would be helpful to assess whether the duration of treatment, the age at which it is initiated or the type of hormone therapy used affects the risks.

“I’m curious to see if the method of administration alters the outcomes,” Ahmed said. “Is one way of giving hormone replacement therapy better or associated with a lower risk of cardiovascular outcomes? If so, then that should be the focus for how we give these patients their hormone replacement therapy going forward.”

In addition to considering ways to mitigate potential cardiovascular risks before starting hormone replacement therapy for individual patients, researchers said it will be important to continue to study potential long-term cardiovascular and other health effects of gender affirmation therapies as the use of these therapies become more common.

Source: American College of Cardiology