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6th June 2022
The post-myocardial infarction (post-MI) mortality risk has been found to be significantly lower among those who are classed as overweight or obese yet much higher for those with a body mass index (BMI) below the ideal range. This was the conclusion of a systematic review and meta-analysis by an international team led by researchers from Aberdeen University, Scotland, UK.
Body mass index (BMI) is a measure of nutritional status in adults and defined as a person’s weight in kilograms divided by the square of the person’s height in metres (kg/m2). Based on the BMI, individuals are deemed to be of normal weight when their BMI is being 18.5 and 24.9. According to the World Health Organization, individuals with a BMI > 25 are classed as overweight, and obese when their BMI is equal to or > 30). According to the American Heart Association, the presence of obesity leads to the development of cardiovascular disease and mortality, independently of other cardiovascular risk factors. However, there is increasing evidence that patients with an elevated BMI may have better outcomes if they develop cardiovascular or renal disease, which is referred to as the “obesity paradox”. Despite this, meta-analyses support a J-shaped relationship between mortality and BMI in patients with coronary artery disease, i.e., the risk is highest for underweight and overweight individuals and lowest for those with a normal BMI.
Nevertheless, whether this same J-shaped relationship holds for post-MI mortality is unknown and was subject of the present meta-analysis. The researchers looked for studies in adults with a previous myocardial infarction where the BMI had been measured and which reported on outcomes such as all-cause mortality, recurrence of an adverse cardiovascular event or hospital re-admission. Hazard ratios (HRs) were used to assess the risk of mortality and the normal BMI (18.5 – 24.9) was used as the reference range for comparative purposes.
Post-MI mortality and BMI
A total of 27 articles with 308,430 participants and with follow-up periods ranging from 6 months to 17 years were included in the analysis.
Among individuals who were classed as overweight (BMI 25 – 29.9) compared to those of normal BMI and based on 8 studies, there as a 15% lower risk of post-MI mortality (HR = 0.85, 95% CI 0.76 – 0.94, p = 0.002). In 14 studies that reported on odds ratios (ORs) rather than hazard ratios, there was also a reduced mortality risk (OR = 0.72, 95% CI 0.64 – 0.81, p < 0.0001).
Among obese patients (BMI > 30) the HR was 0.86 (95% CI 0.81 – 0.91, p < 0.0001) and for morbidly obese patients, although the HR was reduced, it was not statistically significant (HR = 0.89, 95% CI 0.78 – 1.01, p = 0.08).
In contrast, among those with a BMI < 18.5, there was a 42% higher risk of post-MI mortality (HR = 1.42, 95% CI 1.25 – 1.62, p < 0.0001) and again, where studies reported odds ratios, this was also significantly increased (OR = 2.48, 95% CI 1.77 – 3.47, p < 0.0001).
There were no significant effects when comparing the risk of hospital re-admission for those who were overweight, obese and underweight.
The authors concluded that individuals who have a BMI less than the normal range are at a significantly higher risk of post-MI mortality. They called for future studies to examine the prognostic utility of other markers of nutritional status in MI to better identify those at a higher risk of poor clinical outcomes.
De Paola L et al. Body Mass Index and Mortality, Recurrence and Readmission after Myocardial Infarction: Systematic Review and Meta-Analysis J Clin Med 2022
12th May 2022
A higher body fat level in men is associated with an elevated risk of prostate cancer death according to a meta-analysis of prospective studies by researchers from the Nuffield Department of Population Health, Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide and in 2020 there were more than 1.4 million new cases of prostate cancer. Prior evidence indicates that there is a positive association between height and the risk of prostate cancer, with taller men being at a greater risk but also that those with greater adiposity, have an elevated risk of high-grade prostate cancer and prostate cancer death. Moreover, other work suggests that a higher body fat level, based on central adiposity is a more relevant factor and that a higher waist circumference was an important risk factor for prostate cancer.
For the present study, the Oxford team use data from the UK Biobank and focused on men who had originally undergone anthropometric measurements (e.g., height, weight, waist and hip circumference). A subgroup of these men also underwent abdominal MRI and a dual-energy X-ray absorptiometry (DXA) scan and for whom body mass index (BMI), waist and hip circumferences were re-assessed. The primary outcome of interest was prostate cancer as the underlying cause of death. In addition, the researchers combined their Biobank data with other published prospective studies to undertake a dose response meta-analysis.
Higher body fat levels and prostate cancer death
Among a cohort of 21,8237 men with a mean age at recruitment of 56.5 years, over a follow-up period of 11.6 years, 661 men (mean age = 63.1 years), died of prostate cancer.
In a multivariable-adjusted model, there was no statistically significant association of BMI, body fat percentage and waist circumference and prostate cancer mortality. However, for the waist to hip ratio (WHR), this association was significant per 0.05 unit increase (hazard ratio, HR = 1.07, 95% CI 1.01 – 1.14, P for trend = 0.028) when comparing the highest to lowest WHR quartiles.
In the meta-analysis, the hazard ratio was 1.10 (95% CI 1.07 – 1.12) for every 5kg/m2 increase in BMI, 1.03 for every 5% increase in body fat percentage, and 1.06 for every 0.05 increase in WHR.
Using the estimate for the effect of BMI from the meta-analysis, the authors estimated that as approximately 11,900 men died from prostate cancer each year (averaged between 2016 – 2018) and if their estimate was accurate, a reduction in mean BMI of 5kg/m2 would potentially lead to 1309 fewer prostate cancer deaths every year in the UK.
They concluded that men with higher body fat (both total and central) were at a higher risk of death from prostate cancer and that these findings provided a reason for men to maintain a healthy weight.
Perez‐Cornago A et al. Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies BMC Med 2022
29th November 2021
Metformin use in patients with pre-diabetes and a body mass index (BMI) greater than 35 led to a lower incidence of cardiovascular disease. This was the finding of a study presented at the American Heart Association Scientific Sessions 2021.
Metformin is approved both in the US and Europe for use along with diet and exercise to lower blood sugar levels in patients with type 2 diabetes. However, the drug has been shown to reduce the rate of conversion from prediabetes to diabetes. This effect of metformin was identified in a 2002 trial with over 3000 non-diabetic patients who had elevated fasting and post loading glucose concentrations. The results showed that in combination with diet and exercise, metformin reduced the incidence of diabetes in high risk patients.
This has led to an increased ‘off-label’ use of the drug in patients with pre-diabetes, although a recent article in 2020, has suggested that metformin should not be used to treat pre-diabetic patients for three main reasons. Firstly, around two-thirds of pre-diabetics do not go on to develop diabetes. Secondly, a third of patients can return to normal glucose levels and finally, patients with pre-diabetes are not at risk for the microvascular complications of diabetes, thus metformin has no impact on this important outcome. In contrast however, other work has found that the presence of pre-diabetes is associated with an increased risk of cardiovascular disease. Furthermore, the American Diabetes Association (ADA) does suggest that metformin can be considered in pre-diabetic patients with additional risk factors such as a BMI ≥35, if they are age less than 60 years, or have history of gestational diabetes. The ADA also advocates use of the drug in those with a rising haemoglobin A1c despite the use of lifestyle interventions.
For the present study, the researchers turned to a health insurance claims database to examine the extent to which pre-diabetic patients, with or without metformin, developed cardiovascular disease (CVD). For the purposes of their analysis, pre-diabetes was defined by a HbA1c of 5.7-6.4, a fasting glucose 100-125 mg/dL or an oral glucose tolerance test result of 140-199 mg/dL, which is the usual definition of pre-diabetes. Excluded patients were those under 25 years of age and with FDA-approved metformin indications including type 1 diabetes, cardiovascular disease, chronic kidney disease or gestational diabetes.
Analysis of the database identified 149,654 patients with prediabetes, of whom 8,624 (5.8%) were prescribed metformin with an average age of 65.9 years (57.3% female). The average BMI among those prescribed metformin was 33.1 which was significantly different to the non-metformin pre-diabetic group (p < 0.001). In addition, the metformin group had a statistically higher incidence of hypertension (78% vs 61%, p < 0.001) and dyslipidaemia (60% vs 48%, p < 0.001).
After a follow-up period of 2.8 years, 24% of the pre-diabetic cohort developed CVD. When dichotomising results by BMI, among the metformin cohort with a BMI > 35, a lower proportion developed CVD compared to those with a BMI < 35 (21.2% vs 28%, p < 0.001). A similar significant result was observed for gender and BMI, with a lower incidence of CVD among those with a BMI > 35. However, while the proportion of metformin patients under 65 years of age who developed CVD was numerically lower for those with a BMI > 35 (11.3% vs 12.6%), the difference was not statistically significant (p = 0.428).
The authors concluded that among in patients with a BMI > 35, using metformin resulted in a lower proportion of developing CVD over the following three years and that these data supported the recommendations outlined by the ADA.
Murrillo JE et al. Abstract 9819: Real World Data: Off-Label Metformin in Patients with Prediabetes is Associated with Improved Cardiovascular Outcomes. AHA 2021