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Statin therapy provides life-long benefit

16th September 2022

Statin therapy provides life-long protection against cardiovascular disease with a large share of the benefit occurring in later life

The benefits of statin therapy against cardiovascular disease are life-long because a large share of the benefit occurs later in life according to the results of a modelling study by researchers from Queen Mary University of London, UK and presented at European Society of Cardiology congress in Barcelona, Spain.

According to the 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice, the causal role of LDL-C, and other apo-B containing lipoproteins, in the development of atherosclerotic cardiovascular disease, is demonstrated beyond any doubt by genetic, observational, and interventional studies. Statin therapy is designed to lower LDL-C cholesterol and a 2016 meta-analysis of 26 randomised controlled trials with over 170,000 patients, found that all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction, largely reflecting significant reductions in deaths due to coronary heart disease and other cardiac causes. Despite these clear benefits, there is some uncertainty about when to start and how long to persist, with statin therapy, to optimise the effects. In the present study, the UK researchers estimated the accumulation of benefit from statin therapy, according to age of initiation, using a microsimulation model that was developed using data on 118,000 participants of large international statin trials from the Cholesterol Treatment Trialists’ Collaboration and 500,000 individuals in the UK Biobank population cohort. The model used individual characteristics (e.g. age, sex) and disease histories to simulate the annual risk of heart attack, stroke, coronary revascularisation, diabetes, cancer, vascular death and nonvascular death for each participant. Treatment with a standard dose of statin (40 mg daily) was used to estimate the effect of therapy versus no therapy in these scenarios: (1) lifelong therapy (used until death or 110 years of age if earlier), (2) therapy stopped at 80 years of age, and (3) delayed initiation of therapy by five years in participants under 45 years of age. The benefit of statin therapy was measured in quality-adjusted life years (QALYs), which represents the length of life adjusted by health to reflect quality of life. For example, one QALY is equal to one year of life in perfect health. Benefits were also reported separately according to baseline cardiovascular risk, which refers to the likelihood of having a heart attack or stroke in the next 10 years, and is based on age, blood pressure, cholesterol levels, smoking status, and medical conditions

Statin therapy benefits

The researchers found that a large part of QALYs gained with statin therapy accrued later in life. The higher the participants’ 10-year cardiovascular risk, the larger and earlier the statin benefit accrued. Compared with lifelong statins, stopping therapy at 80 years of age, would erase a large share of the potential benefit, especially for people with relatively low cardiovascular risk.

According to lead author of the study Dr Runguo Wu ‘the study indicates that people in their 40s with a high likelihood of developing cardiovascular disease, and people of all ages with existing heart disease, should be considered for immediate initiation of cholesterol lowering treatment. Stopping treatment, unless advised by a doctor, does not appear to be a wise choice.’

They added that ‘our study suggests that people who start taking statins in their 50s but stop at 80 years of age instead of continuing lifelong, will lose 73% of the QALY benefit if they are at relatively low cardiovascular risk and 36% if they are at high cardiovascular risk – since those at elevated risk start to benefit earlier. Women’s cardiovascular risk is generally lower than men’s. This means that for women, most of the lifelong benefit from statins occurs later in life and stopping therapy prematurely is likely more detrimental than for men.’

It was also important to understand that the benefits of statin therapy was dependent upon an individual’s baseline risk. For example, for some one under 45 years of age at low cardiovascular risk, (i.e., less than 5% likelihood of heart attack or stroke in the next 10 years) a five-year delay in taking statins had little impact – they lost just 2% of the potential QALY benefit from lifelong therapy. However, the impact was larger in people under 45 years of age at high cardiovascular risk, meaning a more than 20% likelihood of heart attack or stroke in the next 10 years – they lost 7% of the potential QALY benefit from lifelong therapy. Dr. Wu said: “Again, this is because people at higher cardiovascular risk start to accrue benefit early on and have more to lose by delaying statin therapy than those at low risk.’

Benefit accrual with cardiovascular disease prevention and effects of discontinuation: a modelling study

Higher avocado intake linked with a reduced risk of cardiovascular disease

27th April 2022

A higher avocado intake has been found to be associated with a lower risk of cardiovascular disease in two large prospective studies

A higher avocado intake reduces the risk of cardiovascular disease according to the findings from two large prospective studies reported by researchers from Harvard T.H. Chan School of Public Health, Boston, USA.

Cardiovascular disease (and which also includes coronary heart disease) represents the leading cause of death globally. Interestingly, studies suggest that there is a valid association between several dietary factors and patterns with coronary heart disease. One healthy food is avocado, which contains a large amount (71%) of monounsaturated fatty acids and helps to promote healthy blood lipid profiles, enhancing the bioavailability of fat soluble vitamins and phyto-chemicals from the avocado or other fruits and vegetables. In fact, there are data showing how avocado consumption is associated with a reduced risk of metabolic syndrome and other work has indicated that eating at least one avocado each day provides a beneficial effect on cardio-metabolic risk factors that extended beyond their heart-healthy fatty acid profile. Furthermore, a recent systematic review found that avocado intake increased serum HDL-cholesterol concentrations, prompting the authors to suggest that the association between avocado intake and cardiovascular risk should be confirmed by well-conducted prospective observational studies or long-term trials.

For the present study, the US team examined the association between a higher avocado intake and cardiovascular outcomes. They turned to data held in both the Nurse’s Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), which are two prospective cohort studies which were initiated in the 1970’s and 1980’s respectively. In both of these cohort studies, participants were asked to complete validated questionnaires asking about lifestyle and diet every 2 years and from this information, the researchers were able to determine how much avocado was consumed. This was then categorised as never or less than once a month, 1 – 3 times per month, weekly and > twice a week. The primary outcome of interest was incident cases of total cardiovascular disease, which was a composite of several adverse cardiovascular outcomes e.g., fatal coronary heart disease. The main secondary outcome related to strokes.

Higher avocado intake and adverse cardiovascular outcomes

A total of 68,786 women from the NHS and 41,701 men from the HPFS who were free of cardiovascular disease and stroke at baseline were included and followed for 30 years (median for men was 13.3 years and 14.2 for women). During follow-up there were a total of 14,274 cases of cardiovascular disease (CVD) in both NHS and HPFS.

After adjustments were made for dietary and lifestyle factors, compared to those who did not eat avocados, individuals with a higher avocado intake (> twice/week) week had a 16% lower risk of CVD (hazard ratio, HR = 0.84, 95% CI 0.75 – 0.95) and a 21% lower risk of coronary heart disease (HR = 0.79, 95% CI 0.68 – 0.91). However, there was no significant reduction for stroke.

The authors calculated that for each half serving/day increase in avocado intake, the pooled hazard ratio for CVD was 0.80. In fact, the authors added that by replacing half a serving/day of margarine, butter, egg, yoghurt, cheese or processed meats with the equivalent amount of avocado would be associated with a 16 to 22% lower risk of CVD.

Pacheco LS et al. Avocado Consumption and Risk of Cardiovascular Disease in US Adults J Am Heart Assoc 2022

Should daily coffee intake be part of a healthy diet?

11th April 2022

Studies have shown that daily coffee intake is associated with cardiovascular benefits such as a lower risk of developing CVD and arrhythmias

Coffee intake (whether ground or instant) of at least 2 – 3 cups per day has been found to be associated with significant reductions in the risk of developing cardiovascular disease (CVD), arrhythmias, as well as cardiovascular and all-cause mortality. This is according to the findings of three studies analysing data held within the UK Biobank.

Although coffee contains caffeine, it is also a rich source of phenolic compounds including chlorogenic acids which contribute to coffee’s antioxidant activity. Moreover, coffee intake at midlife has been associated with a lower risk of dementia and Alzheimer’s disease compared with those drinking no or only little coffee. However, the cardiovascular benefits from drinking coffee are less clear with one study finding that in men, the risk of nonfatal myocardial infarction was not associated with coffee drinking. In contrast, a large prospective study observed that coffee consumption was inversely associated with total and cause-specific mortality.

Due to these conflicting results, three studies presented at the American College of Cardiology Scientific Session have examined cardiovascular and mortality benefits disease associated with coffee intake.

In the first study, effects of habitual coffee consumption on incident cardiovascular disease, arrhythmia, and mortality: findings from UK BIOBANK, researchers from the University of Melbourne, Australia, included data from 382,535 individuals with a mean age of 57 years (52% female) and assessed the effect of coffee intake over a 10-year period. The results showed that a coffee intake of 2 – 3 cups/day was significantly associated (for all associations, p < 0.01) with the lowest risk for developing CVD (Hazard ratio, HR = 0.91, 95% CI 0.88 – 0.94), coronary heart disease (HR = 0.90), heart failure (HR = 0.85) and all-cause mortality (HR = 0.86). They found a U-shaped relationship between higher coffee intake and incident arrhythmia which was also lowest at 2 – 3 cups/day (HR = 0.92).

In the second study, regular coffee intake is associated with improved mortality in prevalent cardiovascular disease, the Australian team focused on the effect of coffee in patients with existing cardiovascular disease. With a population of 502,543 individuals, again followed for 10 years, CVD was subsequently diagnosed in 342,279 participants, of whom, 19.6% died. The team found that coffee intake was safe at all levels and that survival was improved again at 2 – 3 cups/day (HR = 0.92, 95% CI 0.86 – 0.99, p = 0.03). Among 24,111 participants diagnosed with an arrhythmia, drinking only one cup of coffee per day was associated with the lowest mortality risk (HR = 0.85) and specifically in those with atrial fibrillation or flutter, one cup of coffee per day was associated with improved survival (HR = 0.82, p < 0.01).

In the third study, ground, instant or decaffeinated coffee? Impact of different coffee subtypes on incident arrhythmia, cardiovascular disease and mortality, the team wondered if there were any differential cardiovascular benefits depending on how the coffee was prepared. Overall, they found that drinking between 1 and 5 cups of coffee per day were associated with a reduced risk of arrhythmia, CVD, CHD, heart failure and stroke. The greatest reduction in risk for CVD was seen with drinking 2 – 3 cups/day of ground coffee (HR = 0.83, 95% CI 0.79 – 0.87) but there was still a significant, albeit smaller, reduction in risk from consuming instant coffee (HR = 0.91, 95% CI 0.88 – 0.95).

Finally, in the third study, the authors showed that drinking 2 – 3 cups/day of decaffeinated coffee was associated with a mortality benefit (HR = 0.85, 95% CI 0.80 – 0.91, p < 0.01), leading the authors to conclude that non-caffeine compounds within coffee are likely to be important factors associated with greater survival among coffee drinkers.

Given these findings, the authors suggested that coffee intake should be considered as part of a healthy diet.

Trial shows that cocoa extract reduces death rate but not overall cardiovascular events

24th March 2022

A cocoa extract given to older adults for three and a half years failed to reduce overall cardiovascular events but did lower the death rate

The use of a cocoa extract containing flavanols did not reduce the overall incidence of cardiovascular events but did lower the incidence of cardiovascular deaths. This was the main finding of a randomised trial by researchers from the Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, US.

Flavan-3-ols, which are a subclass of flavonoids, represent a type of poly-phenolic substances which are present in a range of plants such as cocoa and cocoa containing foods such as chocolate. Furthermore, research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. As well as flavonoids, a cocoa extract typically contains other ingredients such as epicatechin and the methylxanthines, theobromine and caffeine. In fact, studies suggest how the presence of these latter components mediate an increased plasma concentration of epicatechin metabolites that coincides with enhanced vascular effects. To date, much research which has focused on the cardiovascular effect of cocoa containing products such as chocolate, and suggests a small inverse association between consumption and both coronary heart disease and stroke. However, there is a lack of data from large-scale trials, on the cardiovascular benefits of a flavanol-rich cocoa extract which contains all the bioactive compounds present in the cocoa bean.

As a result, the US team undertook the Cocoa Supplement and Multivitamin Outcome Study (COSMOS), a pragmatic, randomised trial which sought to examine the effect of a cocoa extract on cardiovascular disease and cancer in older adults. For the present study, the authors have only reported on the cardiovascular outcomes.

The team recruited adults over 65 years of age, who were initially free of major cardiovascular disease and given either a cocoa extract containing 500 mg/day of cocoa flavanols and a multivitamin supplement or matching placebo. All participants were required to stop taking cocoa supplements (although chocolate could still be eaten) and a blood biomarker of flavanol intake were initially measured and repeated after years 1, 2 and 3. The primary outcome was a composite of total cardiovascular disease (CVD) outcomes including myocardial infarction (MI), stroke, cardiovascular mortality and coronary revascularisation. The authors then set the secondary outcomes as the individual components of the primary outcome, i.e., cardiovascular death, stroke etc.

Cocoa extract and cardiovascular outcomes

A total of 21,442 individuals with a mean age of 72.1 years (59.1% female) were randomised to cocoa (10,719) or placebo and followed for a median of 3.6 years. Based on an analysis of plasma samples, there was a three-fold higher increase compared to placebo, in the levels of flavanol biomarker and this did not differ between follow-up assessment.

During the follow-up period there were 866 confirmed cardiovascular events, 410 in those taking the cocoa extract and 456 in the placebo group, giving a hazard ratio, HR of 0.90 (95% CI 0.78 – 1.02, p = 0.11).

For the secondary outcomes, only cardiovascular death was significantly different (HR = 0.73, 95% CI 0.54 – 0.98).

The authors concluded that while the cocoa extract did not reduce the primary outcome, longer follow-up of trial participants may further elucidate the relationship between consumption of the extract and cardiovascular events.

Sesso HD et al. Effect of Cocoa Flavanol Supplementation for Prevention of Cardiovascular Disease Events: The COSMOS Randomized Clinical Trial Am J Clin Nutr 2022

Higher intake of raw but not cooked vegetables linked to lower CVD risk

1st March 2022

A higher intake of raw but not cooked vegetables appears to be associated with a lower incidence of cardiovascular disease

A higher intake of raw rather than cooked vegetables appears to be linked with a lower incidence of cardiovascular disease (CVD) although this difference might be due to residual confounding. This was the conclusion of a study of patients in the UK Biobank by researchers from the Nuffield Department of Population Health, University of Oxford, Oxford, UK.

The potential health benefits associated with an increased intake of fruit and vegetables has been widely reported for many years. In a 2019 systematic review of studies, the authors noted that the strongest (probable) evidence for increased vegetable intake was for cardiovascular disease protection although there was possible evidence for a reduced risk of colon cancer, depression and pancreatic diseases for fruit intake. These findings were echoed in a 2020 review which reported that current evidence suggests that fruit and vegetable have the strongest effects in relation to prevention of CVDs. Moreover, another study has found that in 2017, 11 million deaths were attributable to dietary risk factors, including 2 million due to a low intake of fruits. In the relation to vegetables, there is little data on the relative benefits of eating either raw (e.g., in salads) or cooked vegetables.

For the present study, the Oxford team used the UK Biobank database to examine the effect of vegetable intake and specifically, the independent effect of raw and cooked vegetables. Within the database, information was collected on the total daily intake of both both uncooked and cooked vegetables. Participants were asked ‘on average how many heaped tablespoons of salad or raw vegetables would you eat per day‘? and the same question but asking specifically about cooked vegetables. The quantities were then categorised as 0, 1 – 2, 3 – 4, and > 5 for raw/cooked vegetables and 0 – 1, 2 – 3, 4 – 7 and > 8 for total vegetable intake. The researcher also collected demographic, co-morbidity and lifestyle factors such as smoking status, amounts of physical exercise etc which were adjusted for in regression models. The primary outcomes were CVD incidence and mortality with secondary outcomes of myocardial infarction, incident stroke and all-cause mortality.

Higher intake of vegetables and CVD risk

A total of 399,586 participants with a mean age of 56.1 years (55.4% female) were included in the analysis and during a median follow-up of 12.1 years, there were 18,052 cases of CVD.

Compared to those consuming the lowest total vegetable intake, participating consuming the highest intake had a 10% lower incidence of CVD (hazard ratio, HR = 0.90, 95% CI 0.83 – 0.97). When separating raw and cooked vegetables, the results were also significant, e.g., for raw vegetables the HR was 0.79 and 0.77 for cooked vegetables.

However, when the models were adjusted for covariates, much of the benefits from raw vegetable intake on CVD incidence were attenuated (HR changing from 0.79 to 0.89) although the result remained significant. In contrast, the association with cooked vegetables was completely attenuated (HR = 1.0, 95% CI 0.91 – 1.09).

Based on these findings, the authors concluded that a higher intake of raw but not cooked vegetables was associated with a lower risk of CVD. Nevertheless, they added a caveat that residual confounding was a likely explanation for much, if not all of the observed associations. In other words, it was possible that there were other, unaccounted for variables, not adjusted for in their models, which might have been important. As such, this means that the results of the study can only demonstrate an association, rather than a causal relationship between intake of raw and cooked vegetables and the risk of incident CVD.

Feng Q et al. Raw and Cooked Vegetable Consumption and Risk of Cardiovascular Disease: a Study of 400,000 Adults in UK Biobank Front Nutr 2022

Caffeine affects regulators of LDL cholesterol to mitigate cardiovascular risk

Caffeine has been found to affect two separate regulators of LDL cholesterol, reducing levels and therefore cardiovascular disease risk

Caffeine affects two regulators of low-density lipoprotein (LDL) cholesterol, reducing levels of the lipoprotein and thereby lowering cardiovascular disease risk (CVD) according to a study by researchers from the Department of Medicine, McMaster University, Hamilton, Canada.

Consumption of caffeine containing beverages has been found to have a nonlinear association with CVD risk, such that the lowest risk is achieved through drinking 3 to 5 cups per day. In addition, there is evidence from cohort studies that coffee consumption reduces the risk of ischaemic and haemorrhagic stroke. However, the mechanism underlying these potentially protective cardiovascular effects remains unclear but could be related to a reduction in risk factors such as LDL cholesterol, which when elevated, is known to be associated with a higher risk of myocardial infarction and atherosclerotic cardiovascular disease.

An important regulator of LDL cholesterol is the membrane-bound transcription factor, SREBP2, that is activated when intracellular cholesterol levels are reduced leading to the production of proprotein convertase subtilisin/kexin type 9 (PCSK9) which reduces the ability of tissues to remove excess LDL from the blood. But how caffeine might affect these two regulators is currently uncertain and was the focus of the study by the Canadian team who examined the impact of caffeine on SREBP2 transcriptional activation.

Caffeine intake and LDL cholesterol levels

Initially using a mouse model, the Canadian team found that caffeine was able to block SREBP2 activation which in turned reduced PCSK9 levels. PCSK9 inhibitors have recently become available for the treatment of high cholesterol and so this was a potentially important observation. Furthermore, the team were also able to show that caffeine increased hepatic cell uptake of LDL, which supported the notion that PCSK9 was attenuated.

In order to study whether this effect could also be seen in humans, the researchers recruited 12 healthy volunteers (4 males) between the ages of 22 and 45. The volunteers were asked to fast for 12 hours and given 400 mg of caffeine, which is roughly four cups of brewed coffee. Blood samples were taken prior to administration of the caffeine and after 2 and 4 hours. The results showed that caffeine reduced plasma levels of PCSK9 by 25% after 2 hours and by 21% after 4 hours and this change was not observed among a group of fasted individuals who were not given caffeine over the same time period.

In discussing their findings, the authors described how their data support the notion that small molecules such as caffeine, by blocking the activation of SREBP2, had a downstream effect of attenuating PCSK9 expression in humans. Furthermore, the overall effect of this action was increased expression of LDL receptors on the surface of hepatocytes (which is blocked by PCSK9) enabling increased cellular uptake of LDL cholesterol and therefore lowering plasma levels.

They concluded that the study offers compelling evidence for the development of caffeine-related compounds that might be able to mitigate the risk of cardiovascular disease.

Lebeau PF et al. Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance Nat Commun 2022

Breastfeeding linked to reduced risk of maternal cardiovascular disease

28th January 2022

Breastfeeding has been found to be associated with a reduced risk of maternal cardiovascular disease levels in later life

Breastfeeding mothers have a lower risk of subsequent cardiovascular disease in later life according to a meta-analysis by researchers from the Department of Neurology, Clinical Epidemiology Team, Medical University of Innsbruck, Innsbruck, Austria.

The World Health Organization has decreed that ‘breastfeeding is one of the most effective ways to ensure child health and survival‘ adding how breastmilk is an ideal food for infants as it is safe, clean and contains antibodies which help protect against many common childhood illnesses. Despite this perceived value, a 2019 analysis of breastfeeding in low and middle incomes countries, revealed how only 37% of children under 6 months of age are exclusively breastfed.

While there are clear benefits to children, breastfeeding also appears to benefit the health of lactating mothers, with one review identifying how breastfeeding for longer than 12 months was associated with a 26% reduced risk of breast cancer and a 32% reduced risk of ovarian cancer. In 2021, a statement from the American Heart Association, suggested that ‘lactation and breastfeeding may lower a woman’s later cardiometabolic risk‘. Furthermore, an umbrella review of the association between maternal health and cardiovascular disease in later life, also suggested an inverse association between length of lactation and morbidity or mortality from cardiovascular disease but did not provide a pooled estimate of this association.

For the present study, the Austrian team undertook a systematic literature review and meta-analysis to more precisely characterise the association between breastfeeding and the development of maternal cardiovascular events. They compared ‘ever’ versus ‘never’ breastfeeding in relation to cardiovascular disease (CVD), coronary heart disease (CHD), stroke or fatal CVD and calculated hazard ratios for each of these outcomes.


The team identified 8 relevant prospective studies which included 1,192,700 women with a mean age of 51.3 years, of whom 82% reported having ever breastfed for a mean duration of 15.6 months.

There was a significant 11% reduced risk of maternal CVD among those breastfeeding compared to who did not (Hazard ratio, HR = 0.89, 95% CI 0.83 – 0.95). Similarly, significant reductions were also observed among those breastfeeding for CHD (HR = 0.86), stoke (HR = 0.88) and fatal CVD (HR = 0.83).

The authors calculated that each additional year of breastfeeding resulted in significant reduced risk, based on hazard ratios, for CVD (HR = 0.91) and CHD (HR = 0.89) and although the risk for stroke was reduced (HR = 0.91) this was non-significant.

Commenting on these results, the authors noted how the relationship between breastfeeding and cardiovascular risk had been overlooked for a long time and that in general, the maternal health benefits are less well known. They suggested that interventions to promote and facilitate breastfeeding should be reinforced.


Tschiderer L et al. Breastfeeding Is Associated With a Reduced Maternal Cardiovascular Risk: Systematic Review and Meta‐Analysis Involving Data From 8 Studies and 1 192 700 Parous Women. J Am Heart Assoc 2022

High psychosocial stress independently associated with increased risk of CVD and death

10th January 2022

High psychosocial stress among people from low-, medium- and high income countries is significantly associated with both CVD and mortality

High psychosocial stress levels has been found to be significantly associated with an increased risk of cardiovascular disease (CVD) and all-cause mortality among those from low, middle and high income countries. This was the conclusion of a study by researchers from the School of Public Health and Community Medicine, University of Gothenburg, Sweden.

Cardiovascular diseases are known to be the leading cause of death across the world, resulting in the loss of around 17.9 million lives each year. The role of high psychosocial stress due to pressures at work in the development of CVD appear to be significant among men but not women, although given that self-reported stress is entirely subjective, it can be difficult to draw any firm conclusions over such associations. In fact, while psychosocial stress appears to be independently associated with CVD, this is highly dependent on the degree and duration of stress as well as the individual response to a particular stressor.

Evidence for the association between high psychosocial stress and the development of CVD and mortality from low and middle income countries is limited and for the present study, the researchers turned to data from the Prospective Urban Rural Epidemiology (PURE) study which was designed to examine the relationship of societal influences on human lifestyle behaviours, cardiovascular risk factors, and incidence of chronic noncommunicable diseases. The study includes individuals aged 35 to 70 years in 27 countries across 5 continents.

The researchers developed a composite measure of stress based on an assessment of psychological, life event and financial stress. Psychological stress was assessed based on questions related to stress at work and home, in which stress was defined as feeling irritable or filled with anxiety or having sleep difficulties as a result of conditions at home or work. Life events stress was assessed in terms of major adverse events such as loss of income, death of a spouse etc and financial stress was dichotomised as little/none, moderate or high/severe. The composite stress score ranged from 0 (none), 1 (low stress), 2 (moderate stress) and 3 (high stress). In regression analysis, the researchers adjusted for several covariates including age, sex, country income, marital status, education etc. The outcomes of interest were major CVD events (e.g., stroke, myocardial infarction, heart failure) and all-cause mortality.


A total of 118, 706 participants with a mean age of 50.4 years (58.8% women) without prior CVD were included and followed by for a median of 10.2 years.

Among the cohort, 7.3% were deemed to have high psychosocial stress, 18.4% moderate stress, 29.4% low stress and 44.8% no stress.

During the period of follow-up, there were 7428 deaths and 5934 major CVD events and compared to those reporting no stress and after adjustment for covariates, the risk of both outcomes of interest increased with higher stress levels. For example, the risk of death increased from 9% (adjusted hazard ratio, aHR = 1.09, 95% CI 1.03 – 1.16) among those with low stress to 17% (aHR = 1.17, 95% CI 1.06 – 1.29) for those with high psychosocial stress. In addition, high psychosocial stress, but not either low or moderate, was also significantly associated with CVD (aHR = 1.22, 95% CI 1.08 – 1.37) and stroke (aHR = 1.30).

The authors concluded that all levels of psychosocial stress were independently associated with a higher risk of CVD and death and suggested that these findings emphasised the need for the development and evaluation of strategies to determine whether stress modification might reduce CVD.


Santosa A et al. Psychosocial Risk Factors and Cardiovascular Disease and Death in a Population-Based Cohort From 21 Low-, Middle-, and High-Income Countries JAMA Netw Open 2021

Low dose aspirin used by nearly half of those over 70 for primary prevention

4th January 2022

Low dose aspirin use was found in nearly half of patients over 70 years of age for primary prevention despite recommendations against its use

The use of low dose aspirin as a primary prevention strategy was found in nearly half of patients aged 70 years of age and older despite current recommendations against its use in this age group. This was an important finding of an analysis by researchers from the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Diseases, Baltimore, US.

Low dose aspirin (LDA) has antithrombotic effects and has been used to reduce the incidence of cardiovascular events such as a myocardial infarction as both a primary and secondary preventative strategy. However, in recent years, the value of LDA for primary prevention, especially in those aged 70 years and older has been questioned, given the increased incidence of major haemorrhage. US guidance in 2019 from the American College of Cardiology and American Heart Association, states that ‘Low-dose aspirin (75-100 mg orally daily) should not be administered on a routine basis for the primary prevention of ASCVD (atherosclerotic cardiovascular disease) among adults>70 years of age.’ Similarly, the European Society of Cardiology also do not recommend aspirin use in those 70 years of age and older who are free from cardiovascular disease.

Given this clear recommendation against the use of LDA in the elderly, for the present study, the US researchers examined trends in the use of aspirin over the past two decades (1998 to 2019) in both primary and secondary prevention and to determine the factors associated with use in both scenarios. Data were obtained from the Behavioural Risk Factor Surveillance (BRFSS), which represents a nationally representative telephone survey of adults across the US. The researchers focused on adults aged 40 years and over to examine trends in aspirin use and individuals were given a score of 0 to 5, based on the presence of cardiovascular risk factors.


Low dose aspirin use increased between 1998 and 2009 from 29% to 37.5% but then decreased from 35.6% (2011) to 33.5% in 2019.

In 2019, 54,388 participants aged 40 years and older responded to questions on aspirin use in BRFSS and overall, 33.5% of them were using the drug. Among those without cardiovascular disease, LDA use was reported by 27.5% for primary prevention and 69.7% for secondary prevention. However, 45.6% of adults > 70 years of age reported using aspirin as a primary preventative strategy. In addition, 12.6% of aspirin users had a score of 0 (i.e., no cardiovascular risk factors).

Among those without any cardiovascular risk factors, males had a higher odds of primary prevention LDA use (adjusted odds ratio, aOR = 1.60, 95% CI 1.12 – 2.27) as did adults aged 70 years and older (aOR = 3.22, 95% CI 2.27 – 4.55) compared to those aged 40 to 69 years. A further factor associated with a higher odds of aspirin use for primary prevention was healthcare coverage (aOR = 2.28).

The authors concluded that despite declines in overall aspirin use, a significant proportion of elderly patients were prescribed the drug and that given the potential risks, clinicians should discuss these risks with a view to discontinuing the drug.


Boakye E et al. Aspirin for cardiovascular disease prevention among adults in the United States: Trends, prevalence, and participant characteristics associated with use. Am J Prev Cardiol 2021

Aspirin use linked to increased risk of heart failure

29th November 2021

Aspirin use among patients both with and without cardiovascular disease is associated with an increased risk of incident heart failure

Aspirin use is associated with an more than a 20% increased risk of heart failure in those with and without cardiovascular disease according to the results of an analysis by researchers from the Research Unit Hypertension and Cardiovascular Epidemiology, University of Leuven, Belgium.

Heart failure (HF) is best described as a clinical syndrome and which is characterised by symptoms including breathlessness, ankle swelling and fatigue, due to structural and/or functional cardiac abnormality, leading to a reduced cardiac output and/or intra-cardiac pressures at rest or during stress. Furthermore, HF is associated with a associated with a hyper coagulable state and autopsy studies have found that acute coronary events are frequent in HF patients who die suddenly, highlighting the potential value of using anti-thrombotic therapy. Although low dose aspirin is no longer recommended for the primary prevention of cardiovascular disease, the role of anti-thrombotic therapy in heart failure is less clear with one study concluding that there was ‘no evidence that aspirin is effective or safe in patients with heart failure.’ In contrast, a 2014 study concluded that ‘low-dose aspirin therapy was associated with a significant reduction in mortality and morbidity risk’ in patients with heart failure.

With some uncertainty over the value of aspirin use in patients with HF, the Belgian researchers sought to gain a better understanding of the role and value of aspirin. They turned to the Heart ‘Omics’ in aGEing (HOMAGE) database, which contains patient-level data for over 30,000 individuals from 21 studies and developed models to examine the impact of aspirin using both a derivation and validation set. At baseline all participants were free of heart failure and at the time of entry into studies, aspirin use was recorded and patients dichotomised as either ‘users’ or ‘non-users’. Other data included in the subsequent analysis were demographics and relevant clinical information such as the presence of co-morbidities and any history of cardiovascular disease.


In the HOMAGE dataset, the study population included 30,827 individuals (19,257 in the derivation set) with a mean age of 66.8 years (33.9% women). Overall, 26.4% had a a history of coronary artery disease and the biggest co-morbidity was hypertension (85.8%).

After a median follow-up period of 5.3 years, 1330 patients experienced either fatal or non-fatal HF with an incident rate of 14.5% (95% CI 13.4 – 15.7%) in the aspirin use group versus 5.9% (95% CI 5.5 – 6.4%) in the ‘non-aspirin’ group. In the HOMAGE dataset, the fully adjusted hazard ratio for aspirin use in those with cardiovascular disease was 1.26 (95% CI 1.12 – 1.41, p < 0.001) and 1.23 (95% CI 1.06 – 1.41, p = 0.004) among those without cardiovascular disease.

Commenting on these findings, the authors concluded that aspirin use increased the risk of incident HF in patients with and without prior cardiovascular disease, adding that ‘our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF.’


Mujaj B et al. Aspirin use is associated with increased risk for incident heart failure: a patient‐level pooled analysis. ESC Heart Fail 2021