Tag: Heart Attack

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Gout flares associated with subsequent cardiovascular events

Gout flares associated with subsequent cardiovascular events

Experts at the University of Nottingham, in collaboration with experts at Keele University, have found that the risk of heart attacks and strokes temporarily increases in the four months after a gout flare.

The research showed that gout patients who suffered from a heart attack or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the 61-120 days prior.

The results of the study, led by Professor Abhishek in the School of Medicine at the University of Nottingham, are published in the journal JAMA.

Gout is a common form of arthritis that affects one in 40 adults in the UK. It is caused by high levels of uric acid, a chemical produced by breakdown of tissues in the body and present in certain foods and drinks.

At high levels, uric acid is deposited in and around joints as needle shaped urate crystals. Once released from their deposits, these crystals cause severe inflammation manifesting as joint pain, swelling, redness, and tenderness that often lasts for 1-2 weeks. These episodes, called gout flares, often recur. Inflammation is also a risk factor for heart attack and stroke.

People with gout tend to have more cardiovascular risk factors, although there have been no previous studies about whether gout flares are linked with an increased risk of heart attack and stroke. In this study, the experts examined whether there was a temporary increase in risk of heart attack or stroke after a gout flare.

The team used anonymized data from 62,574 patients with gout treated in the National Health Service in the UK. Of these, 10,475 experienced heart attack or stroke after the diagnosis of gout, while others of similar age, sex, and duration of gout, did not experience such events. They evaluated the association between heart attacks or strokes and recent gout flares and adjusted these results for comorbidities, socioeconomic deprivation, lifestyle factors and prescribed medications among other things. They found that gout patients who suffered a heart attack or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the preceding 61-120 days.

They found a similar high rate of heart attack or stroke in the 0-60 and 61-120 days after gout flares compared with other time periods, when they used information from only patients who consulted for a gout flare and also experienced either heart attack or stroke. This further strengthened the finding that gout flares are associated with a transient increase in cardiovascular events following flares. The increased odds and rates persisted when people with pre-existing heart disease or stroke before their gout diagnosis were excluded, and when shorter exposure periods such as 0-15 and 16-30 days prior to heart attack or stroke, were considered.

Gout patients who died from a heart attack or stroke had over four times the odds of experiencing a gout flare in the preceding 0-60 days and over twice the odds of gout flare in the preceding 61-120 days.

This is the first study of its kind to examine whether there is an association between recent gout flares and heart attacks and strokes.


The results show that among patients with gout, patients who experienced a heart attack or stroke had significantly increased odds of a gout flare during the preceding 120-days compared with patients who did not experience such events. These findings suggest that gout flares are associated with a transient increase in cardiovascular events following flares.


People with recurrent gout flares should be considered for long-term treatment with urate lowering treatments such as allopurinol. This is a reliable way of removing urate crystal deposits and providing freedom from gout flares. Patients should also be considered for concurrent treatment with anti-inflammatory medicines such as colchicine for the first few months because urate lowering treatments may trigger gout flares in the short term.


People with gout should be encouraged to adopt a healthy lifestyle with appropriate treatment of conditions such as high blood pressure, high cholesterol, obesity and diabetes to minimise their background risk of heart attack and stroke”


Professor Abhishek, lead author on the study

Source:

Journal reference:

Cipolletta, E., et al. (2022) Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout. JAMA. doi.org/10.1001/jama.2022.11390.

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Analysis finds little proof that testosterone treatment increases the risk of cardiovascular events

Analysis finds little proof that testosterone treatment increases the risk of cardiovascular events

Testosterone replacement therapy appears safe in the short-to-medium term to treat a condition caused by deficiency of the male sex hormone, according to the most comprehensive analysis of the treatment to date, published in The Lancet Healthy Longevity journal.

The findings suggest that men given testosterone to treat hypogonadism are at no greater risk of heart attack, stroke, and other cardiovascular events in the short-to-medium term than men who do not receive testosterone treatment.

Testosterone replacement therapy is the standard treatment for hypogonadism, which can cause sexual dysfunction, weakening of bones and muscles, and reduced quality of life. Risk factors for the condition include aging (as testosterone levels decline with age), obesity (BMI of 30 kg/m2 or above), and diabetes.

Despite being widely used, the cardiovascular safety of testosterone treatment has until now remained unclear due to inconsistent findings. This is because most previous clinical studies have relied on aggregate data, rather than individual participant data and have not published details of individual adverse events.

Prescribing of testosterone for hypogonadism is increasing globally, but conflicting messages about its safety may have led to many patients not receiving the treatment. Ongoing studies should help to determine the longer-term safety of testosterone but, in the meantime, our results provide much-needed reassurance about its short-to-medium term safety. Our findings could have important implications for the treatment of men with hypogonadism worldwide.”


Jemma Hudson, Study Lead Author, University of Aberdeen

The authors conducted a systematic review identifying 35 eligible clinical trials published since 1992, of which 17 provided individual participant data. A blinded analysis by two independent clinicians enabled the classification of every cardiovascular event, allowing for a more robust analysis of the cardiovascular safety of testosterone treatment.

A meta-analysis using individual participant data from 17 studies and a further meta-analysis integrating these data with the aggregate data provided by the 18 trials that did not provide individual participant data were performed.

Among the 17 trials with individual patient data, 1,750 participants received testosterone and 1,681 were given a placebo. The average length of testosterone treatment was 9.5 months. The average age of participants was 65 years, and most were white and did not smoke. Participants’ average BMI was 30 kg/m2, which is considered obese.

A meta-analysis showed there were 120/1,601 (7.5%) cardiovascular events in the testosterone group and 110/1,519 (7.2%) in the placebo group across 13 trials that provided this information. Patient age, smoking or diabetes status did not affect cardiovascular risk. Similarly, there was no significant difference in mortality rate between the testosterone group (6/1,621 deaths, 0.4%) and the placebo group (12/1,537 deaths, 0.8%) across the 14 trials that provided individual patient data on mortality, but only limited data were available.

The researchers also found that testosterone significantly reduced serum total cholesterol, high-density lipoprotein (HDL), and triglycerides compared with placebo. However, there were no significant differences in serum low-density lipoprotein (LDL), blood pressure, glycaemic parameters, diabetes incidence, and prostate adverse outcomes between the testosterone and placebo groups.

The meta-analysis that integrated individual participant data with aggregate data showed similar results.

The authors acknowledge some limitations to their study. There was little available data evaluating the cardiovascular safety of testosterone treatment beyond 12 months, and the very small number of deaths recorded during testosterone trials hampered the authors’ ability to analyze why they occurred.

However, the longer-term safety of testosterone treatment is currently being investigated in another clinical trial. While the meta-analysis of aggregate data showed similar results to the one involving individual patient data only, it cannot be ruled out with certainty that a high number of unreported cardiovascular events in the trials that did not provide individual participant data could alter the current conclusions.

Source:

Journal reference:

Hudson, J., et al. (2022) Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. The Lancet Healthy Longevity. doi.org/10.1016/S2666-7568(22)00096-4

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People with elevated blood pressure upon standing more likely to have risk for cardiovascular events

People with elevated blood pressure upon standing more likely to have risk for cardiovascular events

Among young and middle-aged adults with high blood pressure, a substantial rise in blood pressure upon standing may identify those with a higher risk of serious cardiovascular events, such as heart attack and stroke, according to new research published today in the American Heart Association’s peer-reviewed journal Hypertension.

This finding may warrant starting blood-pressure-lowering treatment including medicines earlier in patients with exaggerated blood pressure response to standing.”


Paolo Palatini, M.D., lead author of the study and professor of internal medicine at the University of Padova in Padova, Italy

Nearly half of Americans and about 40% of people worldwide have high blood pressure, considered to be the world’s leading preventable cause of death. According to the American Heart Association’s 2022 heart disease statistics, people with hypertension in mid-life are five times more likely to have impaired cognitive function and twice as likely to experience reduced executive function, dementia and Alzheimer’s disease.

Typically, systolic (top number) blood pressure falls slightly upon standing up. In this study, researchers assessed whether the opposite response – a significant rise in systolic blood pressure upon standing – is a risk factor for heart attack and other serious cardiovascular events.

The investigators evaluated 1,207 people who were part of the HARVEST study, a prospective study that began in Italy in 1990 and included adults ages 18-45 years old with untreated stage 1 hypertension. Stage 1 hypertension was defined as systolic blood pressure of 140-159 mm Hg and/or diastolic BP 90-100 mm Hg. None had taken blood pressure-lowering medication prior to the study, and all were initially estimated at low risk for major cardiovascular events based on their lifestyle and medical history (no diabetes, renal impairment or other cardiovascular diseases). At enrollment, participants were an average age of 33 years, 72% were men, and all were white.

At enrollment, six blood pressure measurements for each participant were taken in various physical positions, including when lying down and after standing up. The 120 participants with the highest rise (top 10%) in blood pressure upon standing averaged an 11.4 mm Hg increase; all increases in this group were greater than 6.5 mm Hg. The remaining participants averaged a 3.8 mm Hg fall in systolic blood pressure upon standing.

The researchers compared heart disease risk factors, laboratory measures and the occurrence of major cardiovascular events (heart attack, heart-related chest pain, stroke, aneurysm of the aortic artery, clogged peripheral arteries) and chronic kidney disease among participants in the two groups. In some analyses, the development of atrial fibrillation, an arrhythmia that is a major risk factor for stroke, was also noted. Results were adjusted for age, gender, parental history of heart disease, and several lifestyle factors and measurements taken during study enrollment.

During an average 17-year follow-up 105 major cardiovascular events occurred. The most common were heart attack, heart-related chest pain and stroke.

People in the group with top 10% rise in blood pressure:

  • were almost twice as likely as other participants to experience a major cardiovascular event;

  • did not generally have a higher risk profile for cardiovascular events during their initial evaluation (outside of the exaggerated blood pressure response to standing);

  • were more likely to be smokers (32.1% vs. 19.9% in the non-rising group), yet physical activity levels were comparable, and they were not more likely to be overweight or obese, and no more likely to have a family history of cardiovascular events;

  • had more favorable cholesterol levels (lower total cholesterol and higher high-density-lipoprotein cholesterol);

  • had lower systolic blood pressure when lying down than the other group (140.5 mm Hg vs. 146.0 mm Hg, respectively), yet blood pressure measures were higher when taken over 24 hours.

After adjusting for average blood pressure taken over 24 hours, an exaggerated blood pressure response to standing remained an independent predictor of adverse heart events or stroke.

“The results of the study confirmed our initial hypothesis – a pronounced increase in blood pressure from lying to standing could be prognostically important in young people with high blood pressure. We were rather surprised that even a relatively small increase in standing blood pressure (6-7 mm Hg) was predictive of major cardiac events in the long run,” said Palatini.

In a subset of 630 participants who had stress hormones measured from 24-hour urine samples, the epinephrine/creatinine ratio was higher in the people with a rise in standing blood pressure compared to those whose standing blood pressure did not rise (118.4 nmol/mol vs. 77.0 nmol/mol, respectively).

“Epinephrine levels are an estimate of the global effect of stressful stimuli over the 24 hours. This suggests that those with the highest blood pressure when standing may have an increased sympathetic response [the fight-or-flight response] to stressors,” said Palatini. “Overall, this causes an increase in average blood pressure.”

“The findings suggest that blood pressure upon standing should be measured in order to tailor treatment for patients with high blood pressure, and potentially, a more aggressive approach to lifestyle changes and blood-pressure-lowering therapy may be considered for people with an elevated [hyperreactor] blood pressure response to standing,” he said.

Results from this study may not be generalizable to people from other ethnic or racial groups since all study participants reported white race/ethnicity. In addition, there were not enough women in the sample to analyze whether the association between rising standing blood pressure and adverse heart events was different among men and women. Because of the relatively small number of major adverse cardiac events in this sample of young people, the results need to be confirmed in larger studies.

Source:

American Heart Association

Journal reference:

Palatini, P., et al. (2022) Blood Pressure Hyperreactivity to Standing: a Predictor of Adverse Outcome in Young Hypertensive Patients. Hypertension. doi.org/10.1161/HYPERTENSIONAHA121.18579.