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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
Patients hospitalised with acute myocarditis (MC) are at an increased risk of all-cause mortality, heart failure, arrhythmias and cardiac arrest compared to matched controls, according to research by a group from the Department of Cardiology, Aalborg University Hospital, Denmark. Inflammation of the cardiac muscle or myocardium (myocarditis) is typically seen in infants and teenagers but can occur at any age. Acute MC symptoms include a stabbing pain and or tightness in the chest which may spread across the body, shortness of breath with light exercise, difficulty in breathing at rest and even flu-like symptoms such as a high temperature, tiredness and fatigue. In addition, acute myocarditis has been shown to be a frequent cause of sudden death in men aged 18 to 28 years of age and in high school athletes. Although evidence points to favourable long-term outcomes in adults with myocarditis, the condition does appear to be associated with an increased risk of cardiovascular and all-cause mortality within 3 months after discharge.
However, there is limited data on the short-term risks of MC, leading the Danish group to retrospectively analysis the outcomes for patients hospitalised with the condition. The researchers turned to the Danish Civil Registration System, which contains information on all registered Danish citizens and can be linked to other administrative databases. Patients were included in the analysis if they had been hospitalised with a primary diagnosis of MC between 2002 and 2018 or as a secondary diagnosis and with a primary diagnosis of heart failure (HF), ventricular tachycardia (VT), ventricular fibrillation (VF), cardiac arrest and cardioverter-defbrillator (ICD). These secondary diagnoses were used because the clinical diagnosis of MC may involve one of these other conditions. Those with myocarditis was age and sex-matched to a population of control patients without a diagnosis of prior MC in a 1:5 ratio. The primary outcome of interest was 90-day all-cause mortality and secondary outcomes were included 90-day presumed cardiovascular causes of death and 90-day risks for HF, a composite of VT or VF or cardiac arrest and ICD. The analysis involved regression modelling with hazard ratios adjusted for age, sex and co-morbidities.
Findings
A total of 15,138 patients were included in the analysis with 2523 with myocarditis who had a median age of 48 years (67.7% male). The 90-day all-cause mortality risk was 4.9% for those with myocarditis versus 0.3% for controls (p < 0.001), with an adjusted hazard ratio, aHR of 22.12 (95% CI 14.44 – 33.88). Similarly, the 90-day risk for HF was 75 times higher (aHR = 75.29, 95% CI 42.54 – 133.23, p < 0.001), as was the risk for the VT/VF composite (aHR = 78.80, p < 0.01) and for ICD implantation (aHR = 65.56, p < 0.01).
Commenting on these results, the authors suggested the myocarditis is a serious disease that is associated with a significantly elevated short-term risk of death. They concluded that “patients with acute myocarditis may benefit from careful diagnostic work-up including cardiac monitoring in the early phase after diagnosis.”
Citation
Kragholm KH et al. Mortality and ventricular arrhythmia after acute myocarditis: a nationwide registry-based follow-up study. Open Heart 2021
9th September 2021
It is often said that breakfast (BF) is the most important meal of the day and there are numerous studies indicating the positive health benefits among those who eat BF. For example, some evidence suggests that not eating breakfast is associated with an increased risk of heart disease, a 21% higher risk of developing type 2 diabetes and a greater risk of all-cause mortality. Nevertheless, while these data are relatively consistent, less is known about which BF foods are potentially associated with a lower incidence and risk of cardiovascular events. One dietary component that is present in common BF foods such as oatmeal, fruit and cereals, is fibre. Furthermore, a recent umbrella review of prospective observational studies concluded that higher fibre intake appears to positively impact on not only cardiovascular disease but overall mortality.
These data led a team from the Department of Family Medicine, West Virginia University School of Medicine, West Virginia, US, to confirm the association between BF, dietary fibre and mortality. The team used the National Health and Nutrition Examination Survey (NHANES) dataset and included individuals aged 40 years and over who self-reported on dietary intake between 1999 and 2002. To determine survival information, the team used a 2015 database which provided mortality follow-up details from the NHANES study. Using the NHANES data, the researchers included those who self-reported as BF eaters and based on the foods eaten, categorised dietary fibre intake as high (> 25 g/day) and low (< 25 g/day). Since hypertension, diabetes and cardiovascular disease can negatively impact on mortality, the analysis included these three factors as covariates. The primary outcomes of the study were all-cause and cardiovascular disease (CVD) mortality and the team included a cohort of non-breakfast eaters which served as a control group.
Findings
A total of 5761 individuals were identified, 4778 BF eaters with a mean age of 57.5 years (46.6% male) and the remainder, a matched cohort of non-breakfast eaters. The average calorie intake was higher in breakfast eaters compared to non-breakfast eaters (2041.1 vs 1871.1, p = 0.001). Furthermore, dietary fibre intake was also higher among BF eaters (16.9g vs 12.8 g, p < 0.0001). During the follow-up period of approximately 147.6 months, there were 2027 (35.2%) all-cause deaths and 469 (8.1%) CVD deaths. After adjustment for covariates, breakfast eaters had a reduced risk of all-cause mortality (adjusted Hazard ratio, aHR = 0.45, 95% CI 0.32 – 0.63) and CVD mortality (aHR = 0.79). Among BF eaters with a fibre intake > 25g/day, there was a 21% reduction in all-cause mortality (aHR = 0.79, 95% CI 0.66 – 0.96) compared to non-breakfast eaters. While there was a trend towards lower CVD mortality among breakfast eaters with fibre intakes > 25g/day, this was not significant (aHR = 0.82, 95% CI 0.50 – 1.35, p = 0.42). Among non-breakfast eaters, there were no significant associations between fibre intake and either all-cause or CVD mortality.
The authors concluded that the mortality benefit from eating breakfast observed in both their own and earlier studies appears to be linked with higher intake of fibre.
Citation
King DE et al. A Relationship Between Mortality and Eating Breakfast and Fiber. J Am Board Fam Med 2021
10th August 2021
According to the UK Kidney Association, chronic kidney disease (CKD) is defined by abnormalities of kidney function or structure and which are present for more than 3 months. This definition will include those with an estimated glomerular filtration rate (eGFR) of less than 60ml/min/1.73m2 on at least two occasions, 90 days part. The condition is common and thought to affect and left untreated, chronic kidney disease is a major cause of kidney failure, leading to around one million deaths per year. Moreover, figures compiled by Kidney Care UK, suggest that around 3 million people in the UK have CKD and that are currently receiving treatment for kidney failure and that between 40 and 45,000 premature deaths occur every use in the UK due to CKD. Globally, it is thought that there are around 840 million people with CKD, acute kidney injury and renal replacement therapy.
While there are several recognised causes of kidney disease, the top two causes are hypertension and diabetes, followed by glomerulonephritis, in which damage occurs to the glomeruli although the condition is usually asymptomatic and only revealed upon testing.
The only known treatments capable of slowing a reduction in kidney function are angiotensin-converting-enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs). Now, a European license extension has been granted to manufacturer, AstraZeneca, for the use of its drug, dapagliflozin (brand name Forxiga), in the treatment of patients with chronic kidney disease, with or without diabetes. Dapagliflozin is a sodium-glucose co-transporter 2 inhibitor and which is indicated for the management of type 2 diabetes as an adjunct to diet and exercise, either alone or in combination with other diabetic treatments. It is also licensed in patients with symptomatic chronic heart failure with a reduced ejection fraction.
Clinical data
The license extension was granted based on the findings of the DAPA-CKD Phase III trial. This was an international, multi-centre, randomised, double-blind, placebo-controlled study in adults with and without type 2 diabetes and who had stage 2 to 4 (i.e., eGFR 25 to 75 ml/min/1.73m2) CKD. A total of 4,304 patients were randomised to either dapagliflozin 10mg or placebo and the primary outcome was a composite of a sustained decline in eGFR of at least 50%, end-stage kidney disease (i.e., stage 5) or death from either renal or cardiovascular causes. The study was terminated early after only 2.4 years when the primary outcome had occurred in 9.2% of those taking dapagliflozin and 14.5% in the placebo arm, giving a hazard ratio, HR, of 0.61 (95% CI 0.51–0.72, p < 0.001). There was also a significant mortality difference between both groups (HR = 0.69, 95% CI 0.53–0.88, p = 0.004) and the effect of taking dapagliflozin was similar in patients with and without type 2 diabetes.
Source: AstraZeneca press release
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