Blood pressure is one of the most important modifiable risk factors for cardiovascular disease. Hypertension significantly raises the risk of stroke, heart failure, coronary heart disease and chronic kidney disease, and is in fact regarded as a cardiovascular disease in its own right.
Managing hypertension has been a subject of considerable controversy over the past few years, with the debate revolving around how aggressively it should be treated, so-called white-coat hypertension, and the importance of home blood pressure monitoring.
Current Australian recommendations were updated in 2016 and include a number of changes from previous guidelines, including a new recommendation for ambulatory or home monitoring in patients with clinic BP of ≥ 140/90 mmHg.
Here are seven key recommendations from the guidelines:
Inflammation has lately become one of the hottest topics in current medical research. Last month, a breakthrough trial presented at the congress of the European Society of Cardiology looks like putting the so-called ‘inflammation hypothesis’ in chronic disease firmly on the map.
The US-based CANTOS trial randomised 10,000 patients who had already survived a myocardial infarction to a drug called canakinumab, which targets the inflammatory pathway interleukin-1 beta but does not affect cholesterol levels. The researchers found a 15% reduction in the risk of myocardial infarction or stroke, and a 30% reduction in the need for a major intervention such as angioplasty or bypass surgery, compared with usual treatment.
The trial won’t be changing clinical practice in heart disease any time soon, not least because canakinumab is a phenomenally expensive drug, and one that also has complex side effects. But the results are nonetheless hugely important, because for the first time researchers have found hard evidence for the role of inflammation in chronic heart disease, independent of lipid levels.
The principal investigator Dr Paul Ridker, a cardiologist at the Brigham and Women’s Hospital in Boston, said the findings have far-reaching implications.
“It tells us that by leveraging an entirely new way to treat patients – targeting inflammation – we may be able to significantly improve outcomes for certain very high-risk populations”.
Another fascinating finding from the study was a substantial reduction in the incidence of lung disease in patients randomised to canakinumab, suggesting that inflammation may play a role in cancer growth as well.
This finding, Dr Ridker said, will “turn the way people look at oncology upside down”.
Heart disease and cancer are hardly the only areas where researchers are looking at how reducing inflammation might reduce risk. Diabetes, HIV, neurodegenerative diseases such as Alzheimer’s or multiple sclerosis, and even depression have been the subject of research.
A study published just this month looks at how inflammation may be implicated in the pathogenesis of Alzheimer’s disease. The brains of people with Alzheimer’s typically have abnormal deposits of two proteins, amyloid beta and tau. US researchers from the University of North Carolina have shown in cell cultures how accumulation of amyloid beta can trigger an inflammatory response, which in turn damages neurons. The type of neuronal damage leads to the formation of bead-like structures containing abnormal tau protein; similar structures as these are found in the brains of people with Alzheimer’s.
Another study has shown that people with fattier, more pro-inflammatory diets tend to have smaller brain volumes and worse cognition.
Brain inflammation may also play a role in depression, according to several recent studies which found high levels of inflammatory markers in the brains of people suffering from the condition. A trial is currently enrolling to trial a biologic called sirukumab for people with major depressive disorder. This drug was initially developed to treat people with rheumatoid arthritis, but when it was trialled in that area, researchers found an interesting side-effect: patients randomised to sirukumab reported having improved moods and less depression.
Targeting inflammatory pathways in the immune system is clearly a promising avenue for drug development, but it’s far from straightforward: dampening the immune response can have dangerous consequences and can promote infection.
For example, sirukumab, the drug being trialled for depression, was recently knocked back by the FDA as a treatment for rheumatoid arthritis, as it had been implicated in several deaths from serious infection and heart disease. Similarly, in the CANTOS trial for heart disease, several deaths from serious infection were reported with canakinumab.
Dr Ridker, the lead researcher on the CANTOS trial, is now enrolling for a second trial, this time testing the anti-inflammatory effects of the immunosupressive drug methotrexate, which has long been used in the treatment of rheumatoid arthritis and whose safety profile is well understood.
Patients will be tracked not only to see if methotrexate lowers risk of cardiovascular events, but also if it reduces cancers. Time will tell, but one thing is certain: the “inflammation hypothesis” is now very much a fixture in the medical research firmament.
The European Society of Cardiology Congress – a key get-together in the cardiovascular world – took place in tragic circumstances in Barcelona this year, just days after the August terrorist attack which killed at least 16 people and left many others injured. While the organisers issued a strong statement of sympathy and solidarity, there was no stopping the Congress which is set to be one of the most important in years, with a number of large trials reporting results.
One of the potential game-changers is the CANTOS trial, involving over 10,000 people with prior myocardial infarction. The trial is testing canakinumab, a monoclonal antibody which targets an inflammatory pathway, for the prevention of major adverse cardiac events. Preliminary results, announced at ESC 2017 and simultaneously published in the New England Journal of Medicine, showed that the drug reduced events by 15% compared with placebo.
Cantos provides long-awaited evidence to bolster the so-called “inflammatory hypothesis” in heart disease. The potential downsides of the treatment are the high cost of the immunotherapy and the fact that it increased the risk of fatal infections.
Another key trial reporting at ESC 2017 is COMPASS, which shows that the novel anticoagulant (NOAC) rivaroxaban plus aspirin improves outcomes in stable cardiovascular disease.
The trial, which randomised over 27,000 patients to various combinations of treatments, found that the addition of rivaroxaban to aspirin reduced the likelihood of myocardial infarction, stroke or cardiovascular death by 24%, improving overall survival by 18%.
Addition of the NOAC did increase the risk of GI bleeding, but not for fatal or cerebral bleeding. Analysis showed that with 23 months of treatment in 1000 patients, the addition of rivaroxaban to aspirin would prevent 13 infarctions or strokes and seven deaths from any cause, at a cost of 12 major bleeds, most of which would be easily treatable.
Here are some other highlights from the congress:
Japanese researchers found that poor sleep is significantly associated with ischaemic heart disease and stroke, in an observational study of 13,000 patients.
Swedish researchers found that in contrast to major guideline recommendations, giving antiplatelet therapy to STEMI patients in the ambulance on the way to the hospital was no better than waiting for in-hospital treatment.
A Swiss team found a reduction in the gender gap in mortality from heart attack. Younger women had been shown to be more likely to die from MI than men of a similar age in previous studies, but that gap has narrowed over the past 20 years.
A substudy of the PRECISION triallooked at the effect of various NSAIDs on blood pressure. Ibuprofen was associated with a significant increase in systolic blood pressure, while celecoxib was not.
Apixaban lowers stroke risk in atrial fibrillation patients undergoing cardioversion, according to late-breaking results from the EMANATE trial.
A 14-year study has found that statins lower the risk of both breast cancer and overall mortality. The huge study involved over a million people.
And finally, married patients with heart disease are more likely to survive than those who are single or widowed, a large study from the ACALM Study Unit has found.
For more information on these and other studies, click here.
The most common method of measuring blood pressure is often inaccurate, a new study has found. This could mean people at risk of serious conditions such as heart disease are missing diagnosis and potentially life-saving treatment.
The so-called “cuff method” involves strapping an inflatable cuff over the upper arm to temporarily cut off the blood supply; then calculating the blood pressure once the cuff is relaxed.
Accurate measurement of blood pressure is regarded among the most important of all medical tests. A misdiagnosis of low blood pressure can be a missed opportunity for lowering a person’s risk of cardiovascular disease, which often presents as a stroke, heart attack or kidney disease. A misdiagnosis of high blood pressure, on the other hand, could lead to people being prescribed unnecessary medication.
What is blood pressure?
Blood pressure is the force exerted in the large arteries – vessels that carry blood away from the heart – with every heartbeat. Blood pressure measurement provides a high (systolic) and a low (diastolic) value. The high value represents the peak pressure during heart contraction; the low value represents the pressure during heart relaxation.
Healthy levels of blood pressure are typically less than 120/80 mmHg (the 120 mmHg is systolic, and 80 mmHg diastolic). Decades of research clearly tell us if a person’s blood pressure is raised they are at higher risk of cardiovascular disease. The higher the blood pressure, the higher the risk.
Although there are many factors to consider when assessing if someone has high blood pressure, the conventional threshold at which doctors might consider giving medication to lower pressure is 140/90 mmHg.
How is blood pressure measured?
The method to measure blood pressure is based on a technique invented in 1896, then refined in 1905, but the basic principal has remained virtually unchanged.
A broad cuff is placed over the upper arm and inflated until the main artery in the arm is completely occluded and blood flow is stopped. The cuff is then slowly deflated until blood flow returns into the lower arm.
A series of signals can then be measured that represent the systolic and diastolic blood pressure. These are measured by either listening with a stethoscope or, more often, using automated devices.
It’s uncertain whether cuff blood pressure accurately measures the pressure in the arteries of the arm or the major artery just outside the heart, called the aorta. This is important as blood pressure readings can be different in these two spots – a potential difference of 25 mmHg or more.
The possibility of big blood pressure differences between the arm and the aorta could result in very different clinical decisions on diagnosis and treatment. So it is important to resolve the uncertainty as to what cuff blood pressure actually measures.
We retrieved data from studies from the 1950s until now that compared cuff blood pressure of more than 2,500 people with that of the gold standard method, called invasive blood pressure. Here, a catheter that measures pressure is inserted inside the artery either at the arm (same site as the cuff) or at the aorta.
Readings from this method were used as a reference and compared with those of the cuff method to determine the accuracy of cuff measurements.
What did we find?
Cuff blood pressure had reasonable accuracy compared with the reference standard, at either the arm or aorta, among people with low cuff blood pressure (lower than 120/80 mmHg) and high cuff blood pressure (the same or higher than 160/100 mmHg). These people are at the extreme ends of the blood pressure risk spectrum.
We found the accuracy when compared to invasive blood pressure was up to 80%.
But for the rest of the population with blood pressure in the middle range – systolic 120 to 159, and diastolic 80 to 99 mmHg – accuracy compared with invasive blood pressure at the arm or the aorta was quite low: only 50% to 57%.
Why is this important?
If people have their blood pressure measured using the cuff method and the values are either low (under 120/80 mmHg) or high (over 160/100 mmHg), we can have reasonable confidence the values are a good representation of the true (invasive) blood pressure.
But for people whose blood pressure is in the most common mid-range of 120 to 160 mmHg systolic or 80 to 100 mmHg diastolic, there is much less certainty as to whether the cuff blood pressure is truly representative of the actual blood pressure.
Our findings do not mean people should stop taking their medication or stop having their blood pressure measured using the cuff device. While this study reveals accuracy issues, the evidence from manylarge clinical trialsclearly shows taking medication to lower blood pressure from high levels reduces the chances of stroke, heart attack and vascular disease.
Cuff blood pressure measurements are still useful, but we could help more people if we could measure blood pressure more accurately. The problem is that some people in the mid blood pressure range may fall through the diagnosis cracks.
Until the accuracy standards of pressure-measuring devices are improved, the best available confirmation of blood pressure levels comes from an average of many repeated measures over time. This is better than one or two measures, as is often the way in busy daily clinical practice, and was closest to the method examined in this study.
Population screening for atrial fibrillation is once more up for discussion as a new study shows that people with newly diagnosed ‘silent’ AF actually have a higher risk of stroke than those with a symptomatic condition.
The study, presented this week at the European Heart Rhythm Association meeting in Vienna, included over 6,000 consecutively enrolled patients with non-valvular atrial fibrillation, of whom around two-thirds were asymptomatic or minimally symptomatic at time of diagnosis.
The study found those with asymptomatic AF had more than double the risk of previous stroke, compared to those who were symptomatic (14.7% vs 6.0%). They were also more likely to have permanent atrial fibrillation than those in the symptomatic group (15.8% vs 8.3%).
But both symptomatic and asymptomatic patients in this study had a similar number of stroke risk factors, with an average CHA2DS2-VASc score of 3.3 for each group.
Lead author Dr Steffen Christow, a cardiologist at Hospital Ingolstadt in Germany, said the higher rate of stroke despite the same number of stroke risk factors may be explained by a longer undiagnosed history of AF in those with asymptomatic disease.
“Our study found that in Western Europe, two-thirds of patients newly diagnosed with atrial fibrillation were asymptomatic. Without detection, patients may not receive appropriate preventive therapy and remain at increased risk of stroke.”
He said the results “underline the urgent need for public programs to detect atrial fibrillation in the general population”.
The current study is a sub-analysis of the GLORIA-AF registry, which characterises a population of newly diagnosed patients with non-valvular atrial fibrillation at risk for stroke, studying patterns, predictors and outcomes of different treatment regimens for stroke prevention.
Medications such as ibuprofen and aspirin, known as non-steroidal anti-inflammatory drugs or NSAIDs, are widely available over the counter from pharmacies and supermarkets. But health providers have known for some time they can be unsafe for people with chronic health problems such as kidney disease, high blood pressure or heart failure.
Two recently published studies have brought back into the spotlight the possible heart-related side effects of NSAIDs. One found an increased risk of heart failure in users of NSAIDs, while another an increased risk of cardiac arrest.
Heart failure is a disease that presents with symptoms such as shortness of breath, fluid retention, leg swelling, and fatigue. This is a result of the heart not being able to pump blood around the body effectively. There are many causes of heart failure, including heart attacks, high blood pressure and excessive alcohol consumption.
A cardiac arrest occurs when the heart stops functioning abruptly and results in complete loss of effective blood flow through the body. The most common cause of a cardiac arrest is a heart attack, where heart muscle is damaged from loss of blood supply due to a blockage in a heart blood vessel. There are many other causes of a cardiac arrest that include structural heart abnormalities and inherited heart diseases of muscle and electrical function.
The recent studies are an important reminder that over-the-counter medicines are not without risk. This class of anti-inflammatory pain killers should no longer be available for sale in grocery stores, but instead restricted to prescription-only or behind-the-counter status in pharmacies.
How they work
Non-steroidal anti-inflammatory drugs are commonly used to relieve pain. They can be either prescribed by a doctor or purchased by the patient over the counter from a supermarket or pharmacy.
NSAIDs are used in a broad range of health conditions associated with pain and inflammation, including types of arthritis, headaches, musculoskeletal injuries and menstrual cramps. Their easy availability, effectiveness and presumption of safety contribute to their widespread use.
They work by inhibiting enzymes called cyclooxygenase 1 (COX-1) and 2 (COX-2). These are involved in a number of internal pathways that result in production of hormone-like substances called prostaglandins, which promote inflammation and increase pain perception.
Prostaglandins also protect the stomach lining from acid, by decreasing acid production and increasing mucus secretion and its neutralising properties. So inhibiting prostaglandins also reduces their protective functions. This is why frequent users of anti-inflammatories may suffer from gastric ulcers.
NSAIDs can either inhibit both COX-1 and COX-2 (non selective) or inhibit COX-2 only (selective). Drugs like ibuprofen and aspirin are non selective and inhibit both the COX enzymes.
COX-1 mediates gastrointestinal, kidney, and clotting function, while COX-2 is induced primarily in states of inflammation and tissue repair. That’s why blocking the COX-2 pathway reduces the effects of inflammation such as fever, swelling, redness and pain.
Importantly, COX-2 inhibition accounts for the anti-inflammatory drug effects of NSAIDs, while COX-1 inhibition can lead to side effects including gastrointestinal ulcers, prolonged bleeding and impaired kidney function. However, it’s not entirely safe for the drugs to inhibit COX-2 only.
Animal studies have shown blocking COX-2 and the subsequent pathway of prostaglandin production may have the unwanted effects of increasing the tendency of blood to clot inside arteries, and a reduced ability of the heart to heal after a heart attack.
In Australia there are only a small number of COX-2 inhibitors available, including Celecoxib and Meloxicam. These are prescription-only medicines and the maximum prescribed dose is at a level at which the heart risks are minimal.
COX-2 inhibitors are used in people who require a non-steroidal anti-inflammatory but have a history of stomach upset or ulcers, or who were thought to be at risk of developing stomach ulcers.
Risk of heart failure
Non-steroidal anti-inflammatory drugs are associated with elevating blood pressure as well as sodium and fluid retention. Both of these effects may unmask previously undiagnosed heart failure, or worsen the symptoms in people known to already have heart failure.
Research published in the British Medical Journal in September 2016 studied 92,163 people admitted to hospital with heart failure, and found NSAID use in the two weeks prior to admission was associated with a 19% increased risk of hospital admission for heart failure. This was compared with people who had not used NSAIDs prior to admission.
The association of NSAIDs with an exacerbation of heart failure was also seen in many older studies. For example, an Australian study in 2000, suggested almost 20% of all heart failure related admissions to hospital may be attributed to recent NSAID use.
Risk of cardiac arrest
Further heart safety concerns with NSAIDs were raised in a recent study from the University of Copenhagen, published in the European Heart Journal.
Data was collected from nearly 30,000 patients who had suffered cardiac arrest between 2001 and 2010. Of these, around 3,500 were found to have been treated with an NSAID within 30 days of having a cardiac arrest.
Use of any NSAID was associated with a 31% increased risk of cardiac arrest. The commonly used non-selective NSAIDs, diclonenac (Voltaren) and ibuprofen were associated with a 50% and 31% increased risk respectively.
It is important to emphasise that in people with no known heart disease and who don’t have any heart risk factors, short term use of these anti-inflammatories carries a minimal increase in heart-related risk.
These recent studies should not create community panic about the safety of NSAIDs when used for short periods of time and at low dosage.
But the high burden of heart disease and heart disease risk factors, such as high blood pressure, obesity and diabetes (which are often unrecognised), warrant a personalised approach to NSAIDs, which weighs the benefits and risks of their use.
This was recommended in the Therapeutic Goods Administration review of the heart related effects of NSAIDs in 2014. These anti-inflammatories should be available for purchase through prescription by a medical practitioner or behind the counter at the pharmacy.