Objectives: To examine associations between sarcopenia, obesity, and sarcopenic obesity and risk of cardiovascular disease ( CVD ) and all‐cause mortality in older men. Design: Prospective cohort study. Setting: British Regional Heart Study. Participants: Men aged 60–79 years (n = 4,252). Measurements: Baseline waist circumference ( WC ) and midarm muscle circumference ( MAMC ) measurements were used to classify participants into four groups: sarcopenic, obese, sarcopenic obese, or optimal WC and MAMC . The cohort was followed for a mean of 11.3 years for CVD and all‐cause mortality. Cox regression analyses assessed associations between sarcopenic obesity groups and all‐cause mortality, CVD mortality, CVD events, and coronary heart disease ( CHD ) events. Results: There were 1,314 deaths, 518 CVD deaths, 852 CVD events, and 458 CHD events during follow‐up. All‐cause mortality risk was significantly greater in sarcopenic ( HR = 1.41, 95% CI = 1.22–1.63) and obese ( HR = 1.21, 95% CI = 1.03–1.42) men than in the optimal reference group, with the highest risk in sarcopenic obese ( HR = 1.72, 95% CI = 1.35–2.18), after adjustment for lifestyle characteristics. Risk of CVD mortality was significantly greater in sarcopenic and obese but not sarcopenic obese men. No association was seen between sarcopenic obesity groups and CHD or CVD events. Conclusion: Sarcopenia and central adiposity were associated with greater cardiovascular mortality and all‐cause mortality. Sarcopenic obese men had the highest risk of all‐cause mortality but not CVD mortality. Efforts to promote healthy aging should focus on preventing obesity and maintaining muscle mass.

Hospitalized COVID-19 patients tend to be older and frequently have hypertension, diabetes or coronary heart disease (CHD), but whether these co-morbidities are true risk factors (i.e. more common than in the general older population) is unclear. We estimated associations between pre-existing diagnoses and hospitalized COVID-19 alone or with mortality, in a large community cohort. UK Biobank (England) participants with baseline assessment 2006 to 2010, followed in hospital discharge records to 2017 and death records to 2020. Demographic and pre-existing common diagnoses association tested with hospitalized laboratory confirmed COVID-19 (16^th March to 26^th April 2020), alone or with mortality, in logistic models. Of 269,070 participants aged 65+, 507 (0.2%) became COVID-19 hospital inpatients, of which 141 (27.8%) died. Common co-morbidities in hospitalized inpatients were hypertension (59.6%), history of fall or fragility fractures (29.4%), coronary heart disease (CHD, 21.5%), type 2 diabetes (type 2, 19. 9%) and asthma (17.6%). However, in models adjusted for comorbidities, age-group, sex, ethnicity and education, pre-existing diagnoses of dementia, type 2 diabetes, COPD, pneumonia, depression, atrial fibrillation and hypertension emerged as independent risk factors for COVID-19 hospitalization, the first five remaining statistically significant for related mortality. Chronic Kidney Disease and asthma were risk factors for COVID-19 hospitalization in women but not men. There are specific high risk pre-existing co-morbidities for COVID-19 hospitalization and related deaths in community based older men and women. These results do not support simple age-based targeting of the older population to prevent severe COVID-19 infections.

This paper reviews the health implications of obesity, sarcopenia and sarcopenic obesity on CVD and mortality in older adults and discusses the obesity paradox seen in patients with CVD. Obesity is a major public health problem with increasing prevalence worldwide. It is an established risk factor for cardiovascular morbidity and mortality in adult populations. However, there is controversy surrounding the effects of obesity as measured by BMI in older people, and overweight and obesity (BMI ⩾ 25 kg/m²) are apparently associated with increased survival in those with CVD (obesity paradox). Ageing is associated with an increase in visceral fat and a progressive loss of muscle mass which have opposing effects on mortality. Thus BMI is not a good indicator of obesity in older adults. Sarcopenia, the age-associated loss of skeletal muscle mass, is a major concern in ageing populations and has been associated with metabolic impairment, CVD risk factors, physical disability and mortality. Sarcopenia often coexists with obesity. Sarcopenic obesity is a new category of obesity in older adults who have high adiposity coupled with low muscle mass. To fully understand the effect of obesity on mortality in the elderly it is important to take muscle mass into account. The evidence suggests that sarcopenia with obesity may be associated with higher levels of metabolic disorders and an increased risk of mortality than obesity or sarcopenia alone. Efforts to promote healthy ageing should focus on both preventing obesity and maintaining or increasing muscle mass.

Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome‐wide association study (GWAS) meta‐analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self‐reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10⁻⁸). Many FI‐associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well‐known disease risk factors and mental health, with particular emphasis on pathways in the brain.

Chia-Ling Kuo, PhD, Luke C Pilling, PhD, Janice L Atkins, PhD, Jane A H Masoli, MBChB, João Delgado, PhD, George A Kuchel, MD, David Melzer, MBBCh PhD; APOE e4

Frailty is a syndrome of growing importance given the global ageing population. While frailty is a multifactorial process, poor nutritional status is considered a key contributor to its pathophysiology. As nutrition is a modifiable risk factor for frailty, strategies to prevent and treat frailty should consider dietary change. Observational evidence linking nutrition with frailty appears most robust for dietary quality: for example, dietary patterns such as the Mediterranean diet appear to be protective. In addition, research on specific foods, such as a higher consumption of fruit and vegetables and lower consumption of ultra-processed foods are consistent, with healthier profiles linked to lower frailty risk. Few dietary intervention studies have been conducted to date, although a growing number of trials that combine supplementation with exercise training suggest a multi-domain approach may be more effective. This review is based on an interdisciplinary workshop, held in November 2020, and synthesises current understanding of dietary influences on frailty, focusing on opportunities for prevention and treatment. Longer term prospective studies and well-designed trials are needed to determine the causal effects of nutrition on frailty risk and progression and how dietary change can be used to prevent and/or treat frailty in the future.