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27th June 2022
Being able to stand on one leg for only 10 seconds is associated with mortality benefits according to the findings of a study by an international team of researchers.
Ageing is known to be associated with a decline in physical fitness yet exercise capacity has been shown, at least in men, to be a more powerful predictor of mortality than other established risk factors for cardiovascular disease. Most aspects of fitness such as aerobic capacity, strength and flexibility will decline with advancing age, although balance tends to be maintained much longer and health-related fitness can be assessed by asking individuals to stand on one leg with their eyes open. Nevertheless, the ability to perform a unipedal stance test has also been found to reduce with age although whether the ability to stand on one leg – which provides a measure of fitness – is associated with a mortality benefit is uncertain.
In the present study, the research team examined if an individual’s ability to stand on one leg for 10 seconds was independently associated with all-cause mortality in a group of middle-aged and older adults. They also explored if the capacity to perform the 10 second unipedal stance added further prognostic value beyond that based on anthropometric and clinical data in mortality risk models. Anthropometric data such as skin fold thickness and waist girth were measured and clinical data were derived from patient’s medical history. For the unipedal stance, individuals were asked to stand on one leg for at least 10 seconds and then categorised as ‘yes’ where the test could be performed or ‘no’ where individuals were unable to perform the test. Using Cox modelling, the researchers assessed survival curves and the risk of death according to whether an individual could successfully perform the unipedal standing test.
Ability to stand on one leg and overall mortality
A total of 1702 individuals with a mean age of 61.7 years (68% women) were included in the study and followed for a median of 7 years.
A total of 20.4% of individuals failed the test, 4.7% of those aged 51 – 55 years and with the proportion rising to 36.8% of those aged 66 – 70 years.
During the follow-up period, 123 participants (7.2%) died, due to cancer (32%), cardiovascular causes (30%) and respiratory disease (9%).
Using a model adjusted for age and other co-morbidities, the risk of death, was significantly higher among those who were unable to perform a stand on one leg for 10 seconds (hazard ratio, HR = 1.84, 95% CI 1.23 – 2.78, p < 0.001).
Using an all-cause mortality model that made use of established risk factors, the C-index was 0.799. However, after addition of the ability to perform the 10 second standing on one leg, the C-index increased to 0.80 (p for comparison = 0.002). In other words, adding the ability to successfully perform the test improved the mortality prediction risk of the model.
The authors concluded that the ability to stand on one leg for at least 10 seconds is independently associated with a reduced risk of all-cause mortality.Citation
Araujo CG et al. Successful 10-second one-legged stance performance predicts survival in middle-aged and older individuals BJSM 2022
17th June 2022
Patients with coronary heart disease (CHD) who continue to be physically active over time and even those who reduce their activity, have a significantly lower risk of all-cause mortality compared to those who remain physically inactive. This was the key finding from a meta-analysis by a team of researchers from Switzerland and Colombia.
Cardiovascular diseases are the leading cause of mortality around the world with an estimated 17.9 million deaths in 2019 and which represented 32% of all global deaths. One modifiable risk factor for cardiovascular disease (CVD) is physical activity and in a 2017 study found that a higher level of recreational and non-recreational physical activity was associated with a lower risk of all-cause mortality and CVD events.
However, whilst there are clear benefits from increased levels of physical activity with respect to all-cause mortality among those with CHD, what is less clear, is the impact of changes in physical activity over time. For the present study, the researchers performed a systematic review and meta-analysis to examine the association between longitudinal trajectories of physical activity and both all-cause mortality and cardiovascular disease mortality in those with CHD. The team included studies with a longitudinal design in adults with CHD and which provided data on all-cause and CVD mortality. For the purposes of the analysis, the researchers examined the changes in all-cause mortality by different levels of reported physical activity trajectories. For example, those who remained inactive, those who increased their physical activity and finally individuals who decreased their activity level over time. For the analysis, hazard ratios were calculated and regression models were adjusted for age, gender, ethnicity, smoking status, alcohol intake and co-morbidities. All of the studies assessed physical activity using validated questionnaires.
All-cause mortality and physical activity trajectories
A total of 9 articles were included in the final analysis, all of which were prospective in nature with 33,576 patients with an overall mean age of 62.5 years and the proportion of women ranging from 18 to 56%.
Compared to those who remained inactive over time, the risk of all-cause mortality was 50% lower among those who remained active (hazard ratio, HR = 0.50, 95% CI 0.39 – 0.63), 45% lower for those who increased their level of activity (HR = 0.55, 95% CI 0.44 – 0.70). Moreover, even among those who had been active but who became less active, there was still a 20% lower all-cause mortality risk (HR = 0.80, 95% CI 0.64 – 0.99).
These reductions in risk were similar for cardiovascular mortality. For example, it was 51% lower for those who remained active (vs inactive) however, it became non-significant for those whose activity levels had reduced over time (HR = 0.91, 95% CI 0.67 – 1.24).
The authors concluded that there was a possible protective mortality benefit of either increased or continued activity among patients with CHD and suggested that physical activity trajectories should be considered in clinical practice.
Citation
Gonzalez-Jaramillo N et al. Systematic Review of Physical Activity Trajectories and Mortality in Patients With Coronary Artery Disease J Am Col Cardiol 2022
12th May 2022
Cancer patients with COVID-19 have been found to be at a greater risk of hospitalisation and 30-day all-cause mortality compared to those without the disease according to the results of a study by a US team from Texas.
The presence of cancer has become a recognised factor that is associated with a higher risk for severe outcomes in those infected with COVID-19 and which is largely due to the presence of a compromised immune system. During the early course of the pandemic, studies observed that a higher proportion of cancer patients infected with COVID-19 were both hospitalised and subsequently died, compared to those without the disease. In contrast, however, other studies have suggested that cancer and non-cancer patients have comparable COVID-19 outcomes after adjusting for age, sex, and comorbidity. Furthermore, the impact of factors such as cancer treatments, different cancer types on COVID-19 related outcomes has been less well studied. For the present study, the US researchers examined the association between cancer-specific characteristics and COVID-19 outcomes. They turned to the Optum de-identified COVID-19 electronic health record, which is derived from over 700 hospitals and 7000 clinics across the USA. Using these data, the researchers examined the outcome of those with a laboratory confirmed COVID-19 and a recorded cancer diagnosis. The primary objective was to determine the effect of cancer on COVID-19 outcomes including 30-day all-cause mortality, hospitalisation, intensive care unit (ICU) admission and ventilator use. These outcomes were also analysed by the nature and type of cancer in comparison to patients without cancer. The authors the explored if there were any other specific factors in those with cancer which impacted on COVID-19 outcomes.
Cancer patient with COVID-19 and related outcomes
A total of 271,639 patients with confirmed COVID-19 of whom 18,460, with a mean age of 66 years (45.3% male) had a cancer diagnosis were analysed. Among those with cancer, 8034 patients had a history of cancer for longer than 12 months and 10,426 had a more recent diagnosis, i.e., within 1 year before COVID-19.
30-day all-cause mortality was more than three times higher among those with cancer (6.8% vs 1.9%) compared to non-cancer patients. After adjustment for age, sex, ethnicity and risk factors, the presence of cancer was associated with a 7% higher risk of death (relative risk, RR = 1.07, 95% CI 1.01 – 1.14, p = 0.028) compared to those without the disease. Similarly, there was a 4% higher risk of hospitalisation (RR = 1.04, 95% CI 1.01 – 1.07, p = 0.006). When comparing the duration of cancer, those with a recent diagnosis had both a significant (p < 0.001) increased risk of mortality (RR = 1.17) and hospitalisation (RR = 1.10) although this risk was non-significant for those who had cancer for much longer.
There was also an increased mortality risk for those with recent metastatic (RR = 2.09), solid tumour (RR = 1.12) and haematological (RR = 1.48) cancers compared with those without the disease. Individual cancers with a significantly elevated risk were leukaemia (RR = 1.58), liver (RR = 2.46), lung (RR = 1.85) and pancreatic (RR = 1.94).
When exploring the factors related to COVID-19 mortality in those with recent cancer, both chemotherapy (RR = 1.37) and radiotherapy (RR = 1.83) within 3-months before COVID-19, were significantly associated with a higher risk of death as was increasing age (i.e., > 75 years) (RR = 6.69). In addition, the only significant co-morbidities were cardiovascular disease (RR = 1.72), diabetes (RR = 1.39) and renal disease (RR = 1.51).
Citation
Kim Y et al. Characterizing cancer and COVID-19 outcomes using electronic health records PLoS One 2022
20th April 2022
The use of sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) in patients with acute, decompensated heart failure is associated with a reduction in adverse cardiovascular outcomes compared with placebo. However, these improvements do not translate into a significant reduction in all-cause mortality, as concluded by a meta-analysis of trials by researchers from the University of Thessaloniki, General Hospital “Hippokration,” Thessaloniki, Greece.
Heart failure (HF) is a complex clinical syndrome characterised by the reduced ability of the heart to pump and/or fill with blood failure. Heart failure is a common problem and globally, the age-standardised prevalence of HF in 2017 was 831.0 per 100,000 people. Moreover, the prognosis of those with more severe HF is poor, with one study finding that among patients hospitalised with HF, the 1-year mortality rate was only 40%.
The sodium-glucose co-transporter 2 receptors are primarily located in the proximal convoluted tubule of the nephron and are responsible for almost 90% to 95% of tubular reabsorption of glucose in the nephron. The SGLT-2Is are a class of drugs originally designed for the management of type 2 diabetes (by preventing glucose re-uptake) although research over the last decade has found that the drugs also have beneficial effects in heart failure. As a result, some members of this class such as empagliflozin, are also licensed in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction.
However, whether these drugs are also effective in patients with acute decompensated HF remains to be determined and was the subject of the meta-analysis by the Greek researchers. The team searched for randomised, controlled trials that enrolled adult patients, irrespective or whether they had diabetes, and who were assigned to a SGLT-2I or placebo or an active comparator. They set the primary safety endpoint as the effect of SGLT-2I on recurrent worsening heart failure (WHF). Several secondary endpoints were used: all-cause mortality; a composite of cardiovascular death or recurrent hospitalisation for HF decompensation and finally, the observed diuretic response. This latter endpoint was defined as the weight change per standard loop diuretic dose. The effects of treatment were assessed using risk ratios (RR).
Sodium-glucose co-transporter-2 inhibitors and heart failure outcomes
The researchers only identified three relevant clinical trials including 1,831 patients.
Compared with placebo, the use of SGLT-2Is produced a signification reduction in the risk of WHF (RR = 0.66, 95% CI 0.58 – 0.76, p < 0.00001). Similarly, there was also a significant 30% reduced risk of the composite endpoint of cardiovascular death or re-hospitalisation for decompensated HF (RR = 0.70, 95% CI 0.62 – 0.78, p < 0.00001). Interestingly, despite these benefits, there was no significant effect on all-cause mortality (RR = 0.72, 95% CI 0.48 – 1.09, p = 0.12) and a non-significant effect on diuretic response, mean difference = – 1.15 (95% CI -3.18 to 0.17, p = 0.26).
Based on their findings, the authors concluded that their data indicated how the use of SGLT-2I drugs significantly reduced recurrent worsening of HF but called for further trials to clarify whether these drugs should become part of the treatment algorithm for HF patients.
Citation
Patoulias D et al. Meta-Analysis Evaluating the Efficacy of Sodium-Glucose Co-Transporter-2 Inhibitors in Patients With Acute or Recently Decompensated Heart Failure Am J Cardiol 2022
11th April 2022
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.
15th March 2022
A mortality benefit accrues from taking more daily steps but this benefit plateaus and depends upon an individual’s age. This was the main finding of a meta-analysis by a team from the Department of Kinesiology and Institute for Applied Life Sciences, University of Massachusetts Amherst, Massachusetts, US.
Measuring the number of steps taken each day has become much easier over the last few years largely because of an increase in the availability of fitness trackers. Moreover, though the idea that the target for beneficial health is at least 10,000 steps/day, there is a lack of evidence to justify this figure. Indeed, it is possible that the actual number of steps/day required could be actually much lower, with one study in older women finding that the mortality rates progressively decreased before levelling at approximately 7500 steps/day. In addition, the optimal number of steps needed to achieve a mortality benefit is likely to be influenced by other factors such as age and gender, as well as the pace of walking, although observational studies have found that there is no significant association between step intensity and mortality after adjusting for total steps per day.
For the present study, the US team set out to assess the mortality benefit derived from the number of steps taken per day and considered how this might be affected by both age and gender. They also sought to clarify if there was an association between the stepping rate (i.e., how fast someone walked) and all-cause mortality. They searched for studies which examined the relationship between daily steps and mortality in adults (> 18 years of age). After identifying relevant articles, the US team asked the study investigators to provide additional data and to calculate the peak 30 and 60 minute stepping rates, as well as the time spent walking at 40 steps/min or faster and 100 steps/min. The primary outcome was set as all-cause mortality. The total number of median daily steps was categorised into quartiles; up to 3553 (quartile 1); 5801 (quartile 2); 7842 (quartile 3) and 10,901 (quartile 4). Hazard ratios were calculated for the mortality benefits and adjusted for several factors including age, sex, education level, body mass index and other health-related variables.
Mortality benefit and daily step count
The authors identified a total of 15 eligible studies which included 47,471 individuals with a mean age of 65 years (68% female) and who were followed-up for a median of 7.1 years. The overall median number of steps was 6495 and individuals under 60 years of age had a higher median number of daily steps compared to those over 60. (7803 vs 5649, under 60 years vs over 60 years of age). In the cohort as a whole, there were 3013 deaths recorded.
Compared to the lowest quartile, the overall adjusted hazard ratio for all-cause mortality in the highest quartile was 0.47 (95% CI 0.39 – 0.57). When comparing those under versus over 60 years of age, there was a greater mortality benefit for older individuals (HR = 0.60 vs HR = 0.43, under 60 vs over 60). In addition, there was a higher benefit for women compared to men (HR = 0.43 vs HR = 0.52, female vs male).
The hazard ratios for mortality plateaued for adults 60 years and older at 6000 – 8000 steps/day and between 8,000 – 10,000 for those under 60 years of age.
The mortality benefit was also significant for a higher step rate for both 30 and 60 minutes but not significant for the time spent walking at 40 or faster, at 100 steps/minute. In other words, didn’t seem to matter if someone walked faster.
The authors concluded that while mortality benefits can be achieved at below the popular reference value of 10,000 steps/day, these benefits plateau and are not increased by taking further steps.
Citation
Paluch AE et al. Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts Lancet Public Health 2022
14th February 2022
The use of anti-hypertensive drugs when combined with healthy lifestyle measures appears to be the best strategy to reduce all-cause and cause-specific mortality. This is according to a study by Chinese researchers from the Department of Epidemiology and Biostatistics, School of Public Health, Huazhong University of Science and Technology, Hubei, China.
Hypertension significantly increases the risks of heart, brain, kidney and other diseases and according to the World Health Organisation, an estimated 1.28 billion adults aged 30-79 years worldwide have hypertension, most of whom are living in low- and middle-income countries. Furthermore, a 2019 analysis calculated that a high systolic blood pressure accounted for approximately 10·8 million deaths which was 19.2% of all recorded deaths in 2019. Hypertension is managed with a range of different classes of medicines, yet non-adherence to anti-hypertensive treatment affects 10%–80% of hypertensive patients and is one of the key drivers of suboptimal BP control. With respect to lifestyle modification, there is strong evidence supporting the benefits of regular physical activity and exercise for the prevention and management of hypertension. However, whether the combination of anti-hypertensive medication and healthy lifestyle measures yields additional benefits and if adoption of healthy lifestyle measures after a diagnosis of hypertension provides a mortality benefit remains uncertain.
For the present study, the Chinese team examined the relationship between anti-hypertensive use and lifestyle measures and the effect of this on all-cause and cause-specific mortality among hypertensive patients. They used data from the Dongfeng-Tongji cohort, which prospectively followed hypertensive patients for a median of 7.3 years. The team assessed specific lifestyle factors including body mass index, smoking status, diet, physical activity and sleep duration and computed an overall lifestyle score based on these five attributes, with higher scores (ranging from 0 to 10) indicating a healthier lifestyle. In addition, participants were categorised into the following subgroups: favourable lifestyle (scores 8 – 10), intermediate (5- 7) and unfavourable (0 – 4). The use of anti-hypertensive medication was dichotomised into yes or no.
Anti-hypertensive use and subsequent mortality
A total of 14,392 participants with a mean age of 65.6 years (50.6% male) using anti-hypertensive medicines were included in the analysis. Over a median of 7.3 years, there were 2015 deaths including 761 due to cardiovascular disease and 525 from cancer. Taking individuals not using anti-hypertensives and following an unfavourable lifestyle as the reference group, individuals using anti-hypertensives and with a favourable lifestyle had the lowest risk of all-cause mortality (hazard ratio, HR = 0.32, 95% CI 0.25 – 0.42). This was also true for cardiovascular mortality (HR = 0.33) and death due to cancer (HR = 0.30).
Interestingly, when using the same reference group, individuals who were not using anti-hypertensives but adopted a favourable lifestyle, also had a lower risk of all-cause mortality (HR = 0.34), cardiovascular (HR = 0.40) and cancer mortality (HR = 0.33). In fact, there was a linear association with lifestyle score and mortality, such that regardless or anti-hypertensive medication use, each 1-point increase in lifestyle score was associated with a 17% lower risk of all-cause mortality, with similar reductions for cardiovascular and cancer deaths.
There was also a reduced mortality risk through the adoption of lifestyle measures after a diagnosis of hypertension. For example, compared to those with a consistently low lifestyle score between baseline and the first follow-up, those who instigated a change in lifestyle score from low to high also had a significantly reduced risk for all-cause (HR = 0.52), cardiovascular (HR = 0.53) mortality although the reduced risk of cancer mortality was non-significant.
The authors concluded that the combined effect of anti-hypertensive medication and adoption of a healthy lifestyle resulted in a significantly reduced risk of all and specific cause mortality.
Citation
Lu Q et al. Association of Lifestyle Factors and Antihypertensive Medication Use With Risk of All-Cause and Cause-Specific Mortality Among Adults With Hypertension in China JAMA Netw Open 2022
25th January 2022
A higher olive oil intake has been linked to a lower all-cause and cardiovascular mortality compared to those who either never or rarely consume it. This was the finding of a study by researchers from the Department of Nutrition, Harvard T.H. Chan School of Public Health, Massachusetts, USA.
Olive oil (OO) consumption has been associated with a myriad of health benefits due to the presence of monounsaturated fatty acids which possess anti-inflammatory and anti-oxidant properties. Moreover, evidence from epidemiological studies show that greater olive oil intake and in-particular, extra virgin olive oil, is associated with a 39% lower risk of cardiovascular disease. Nevertheless, there is a paucity of data on the relationship between total olive oil intake on both all-cause and cause-specific mortality.
For the present study, the Harvard team used data from two ongoing prospective US cohort studies, the Nurses Health Study (NHS) which began in 1976 and the Health professionals Follow-up study (HPFS) which started in 1986. In both studies, participants are sent questionnaires, every two years to assess lifestyle factors and health status and for the present analysis, team used the baseline level of OO intake which was first captured in 1990. For the purposes of the analysis, one tablespoon was considered to be equivalent to 13.5 g of OO. Consumption of olive oil was then categorised by frequency as never or less than once/month (the reference point), > 0 < 1 teaspoon, > 1 to < 2 teaspoons and greater than half a tablespoon (equivalent to > 7 gm/day.
The researchers identified both the total number of deaths during the period of follow-up and the cause from medical records. Multivariable regression analysis was used to estimate the risk of total and cause-specific mortality and models were adjusted for a number of covariates such as age, gender, smoking status, body mass index etc.
Findings
During a 28 year follow-up period, there were 36,856 deaths and the mean OO consumption increased from 1.6g/day in 1990 to 4g/day in 2010.
Among those with the highest intake of OO, compared to the reference category, there was 19% reduced risk of total mortality (Hazard ratio, HR = 0.81, 95% CI 0.78 – 0.87) and cardiovascular mortality (HR = 0.81, 95% CI 0.75 – 0.89). In addition, the researchers found that increased OO intake reduced the risk of cancer and neurodegenerative mortality by 29% and 18% respectively.
In a further analysis, the Harvard team considered the mortality benefits of substituting other sources of fat with olive oil. For example, they calculated that replacing 10 g/day of margarine with an equivalent amount of OO was associated with a 13% lower risk of mortality and similar reductions were seen for butter, mayonnaise and dairy fat. They also observed that these reduced risk were also consistent for other causes of death.
They concluded that greater consumption of olive oil lead to reductions in all-cause and cause-specific mortalities and such reductions in risk could also be achieved when other types of fat were replaced with olive oil.
Citation
Guash-Ferre M et al. Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults J Am Coll Cardiol 2022
10th January 2022
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.
Findings
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.
Citation
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
1st November 2021
A non-fatal myocardial infarction (MI) does not appear to represent a valid surrogate marker for all-cause and cardiovascular (CV) mortality according to an analysis by a researchers from the Department of Medicine, Washington University, US. Surrogate markers and their endpoints are commonly used in clinical trials but a potential problem is that there needs to be some certainty over whether changes in the surrogate are indicative of changes in the final outcome of interest. There are essentially three criteria which need to be met for a surrogate to be deemed valid: a biologically plausible relationship between the surrogate and the final outcome; a consistent association between surrogate and final outcome and that any treatment effect on the surrogate corresponds to a treatment effect on the final outcome. Although there is an abundance of evidence of the association between a non-fatal MI (NFMI) and both all-cause and CV mortality, there is little objective evidence to support the third criteria.
In trying to establish whether a non-fatal MI is a valid surrogate for both types of mortality in trials, the Washington team searched for all randomised studies that considered the treatment or prevention of coronary artery disease and reported a non-fatal MI as an outcome. The inclusion criteria was set as only randomised controlled trials with at least 1,000 patients and 24 months of follow-up. Trial level correlation between NFMI and all-cause and CV mortality was assessed for surrogacy using the coefficient of determination, R-squared, by plotting the individual trial outcome (in this case mortality) against NFMI. The R-squared value corresponds to the explained variation (or association) between these two measures and varies from 0 (no surrogacy) to 1 (perfect surrogacy). The threshold for validating NFMI as a surrogate for all-cause and CV mortality was set at 0.80.
Findings
A total of 144 randomised trials with 5,726,395 patients were included in analysis. In the pooled analysis of these trials, the value of R-squared for all-cause mortality was 0.02 (95% CI 0.0 – 0.08) and 0.11 (95% CI 0.02 – 0.27) for CV mortality. This lack of surrogacy was evident in trials of both primary, secondary and mixed primary/secondary prevention studies. Furthermore, the duration of follow-up had no impact on the association. For example, R-squared was not a surrogate for trials lasting from 2 to 3.9 years (R-squared = 0.004) or even trials with a follow-up of 6 or more years (R-squared = 0.06).
Commenting on their findings, the authors noted that while it is generally assumed that an intervention to reduce NFMI would also reduce all-cause and CV mortality, the results implied that any treatment or intervention designed to reduce a NFMI cannot be assumed to also reduce either all-cause or CV mortality. They also noted that there was a high degree of heterogeneity for the included trials and whilst this is generally considered to be a disadvantage, it actually becomes an advantage for the present analysis as it allows for subgroup analyses to determine if surrogacy exists.
They concluded that while NFMI is not a validated surrogate endpoint for mortality in trials, it’s inclusion may be justified due to the relationship between impaired quality of life and health-care related costs.
Citation
O’Fee K et al. Assessment of Nonfatal Myocardial Infarction as a Surrogate for All-Cause and Cardiovascular Mortality in Treatment or Prevention of Coronary Artery Disease. A Meta-analysis of Randomized Clinical Trials. JAMA Int Med 2021
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