Physical Activity
It is unclear how engaging in physical activity after long periods of inactivity provides expected health benefits. The aim of this study1 was to determine whether physically inactive primary care patients reduce their mortality risk by increasing physical activity, even in low doses.

A cohort of 3,357 physically inactive patients attending 11 Spanish public primary healthcare centres were studied prospectively. Changes in physical activity was repeatedly measured during patients’ participation in the ‘Experimental Program for Physical Activity Promotion’ clinical trial between 2003 and 2006, using the ‘7-day Physical Activity Recall’.

Mortality to December 31, 2018 (312 deaths) was recorded from national statistics, and survival time from the end of the clinical trial analysed using proportional hazard models. The results were that after 46,191 person–years of follow-up, compared with individuals who remained physically inactive, the mortality rates of those who achieved the minimum recommendations of 150–300 min/week of moderate- or 75–150 min/week of vigorous-intensity exercise was reduced by 45 per cent.

Those who did not meet these recommendations but increased physical activity in low doses, that is, 50 min/week of moderate physical activity, showed a 31 per cent reduced mortality and, those who surpassed the recommendation saw a 49 per cent reduction in mortality.

The inverse association between increased physical activity and mortality follows a continuous curvilinear dose–response relationship. The authors concluded that physically inactive primary care patients reduced their risk of mortality by increasing physical activity, even in doses below recommended levels. Greater reduction was achieved through meeting physical activity recommendations or adopting levels of physical activity higher than those recommended.

The study’s results tie in nicely with a meta-analysis examining the dose–response relationship between steps per day and cardiovascular disease (CVD).2 Eight prospective studies (20,152 adults) were included with device-measured steps and participants followed for CVD events.

Studies quantified steps per day and CVD events were defined as fatal and non-fatal coronary heart disease, stroke, and heart failure. The mean age of participants was 63.2 years and 52 per cent were women. The mean follow-up was 6.2 years (123,209 person-years), with a total of 1,523 CVD events (12.4 per 1,000 participant-years) reported.

For older adults (aged > 60 years) CVD risk was halved and the authors concluded that taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician–patient communication and population health to reduce the risk of CVD.

With all this increase in physical activity, are there any downsides? What is the risk of sudden death for example? The answer is quite low. In this study, the authors investigated the prevalence and characteristics of sports-related sudden cardiac arrest (SrSCA) among subjects ≥65 years of age in a large U.S. population.3 All out-of-hospital sudden cardiac arrests (SCAs) were prospectively ascertained in Portland, Oregon (2002-2017), and Ventura County, California (2015-2021).

The catchment population was approximately 1.85 million. Detailed information was obtained for SCA warning symptoms, circumstances, and lifetime clinical history. Subjects with SCA during or within one hour of cessation of sports activity were categorized as SrSCA. Of 4,078 SCAs among subjects ≥65 years of age, 77 were SrSCA (1.9 per cent; 91 per cent men).

The crude annual SrSCA incidence among age ≥65 years was 3.29/100,000 in Portland and 2.10/100,000 in Ventura. The most common associated activities were cycling, gym activity, and running. SrSCA cases had lower burden of cardiovascular risk factors as well as comorbidities compared with non-SrSCA. The authors conclude that the risk of SrSCA is low, and probably outweighed by the high benefit of exercise.

Physical activity has other benefits. Lifestyle intervention consisting of diet and regular exercise has proved to be effective for prevention of type 2 diabetes in individuals at high risk. In this study, the authors conducted a 10-year follow-up study based on their previous randomized clinical trial to assess the long-term effects of exercise on the prevention of diabetes.4

The randomized clinical trial of 12-month intervention consisted of vigorous aerobic exercise (n = 73), moderate aerobic exercise (n = 73), and non-exercise control groups (n = 74) in participants with central obesity and non-alcoholic fatty liver disease. Over the 10-year follow-up, the cumulative incidence of type 2 diabetes was 2.1 per 100 person-years (PYs), 1.9 per 100 PYs, and 4.1 per 100 PYs, respectively in the vigorous, moderate, and non-exercise groups.

The risk of diabetes was reduced by 49 per cent in the vigorous aerobic exercise group and by 53 per cent in the moderate aerobic exercise group compared with the non-exercise Group. The results are supportive of physical exercise as an effective scheme for obesity management to delay the progression of type 2 diabetes. Vigorous and moderate aerobic exercise programs could be implemented for prevention of type 2 diabetes in people with obesity.

References:

1. Grandes G et al. Any increment in physical activity reduces mortality risk of physically inactive patients: prospective cohort study in primary care. Br J Gen Pract 2022; doi: https://doi.org/10.3399/BJGP.2022.0118.
2. Paluch AE et al. Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis. Circulation 2022. Originally published Dec 20, 2022. https://doi.org/10.1161/CIRCULATIONAHA.122.061288 Circulation. 2022;0.
3. Holmstrom L et al. Sudden Cardiac Arrest During Sports Activity in Older Adults. J Am Coll Cardiol EP. Jan 18, 2023. Epublished doi: 10.1016/j.jacep.2022.10.033.
4. Chen Y et al. Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults With Obesity: A 10-Year Follow-up of a Randomized Clinical Trial. JAMA Intern Med. Published online January 30, 2023. doi:10.1001/jamainternmed.2022.6291.

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Covid-19
The protective efficacy of vaccination is of interest to us all. What works best, for whom and for how long? The global surge in the omicron and other variants has resulted in many individuals with hybrid immunity (immunity developed through a combination of SARS-CoV-2 infection and vaccination).

This systematic review and meta-regression analysis studied the protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant causing severe Covid-19 disease.1 The researchers found that all estimates of protection waned within months against reinfection, but remained high and sustained for hospital admission or severe disease. Individuals with hybrid immunity had the highest magnitude and durability of protection, and as a result might be able to extend the period before booster vaccinations are needed, compared to individuals who have never been infected.1

A cohort study from Hong Kong looked at the efficacy of booster vaccination with inactivated whole virus or mRNA vaccines and Covid-19–related deaths among people with multimorbidity during the initial Omicron wave of the Covid-19 pandemic.2

The authors found that among people with multimorbidity, booster vaccination with BNT162b2 or CoronaVac was associated with reductions of more than 90 per cent in Covid-19–related mortality rates compared with only two doses. These results highlight the crucial role of booster vaccination for protecting vulnerable populations. One wonders if the efficacy of the vaccine would be as high against more recent variants. The following two publications discuss this issue.

A research letter from Qatar published in the NEJM strikes a more cautious note.3 The researchers estimated the effectiveness of previous infection with SARS-CoV-2 in preventing reinfection with BA.2.75 using a test-negative, case–control study design. The found that protection afforded by a previous pre-omicron infection was negligible at this stage of the pandemic, a finding that confirms that pre-omicron–conferred immunity against omicron infection may not last beyond approximately one year.

Protection conferred by a previous omicron infection was moderate, at approximately 50 per cent, when the previous infection was with a BA.1 or BA.2 subvariant but was approximately 80 per cent when the previous infection was more recent (i.e., caused by a BA.4 or BA.5 subvariant); these results may reflect a combination of progressive immune-system evasion and gradual waning of immune protection.

Immunity resulting from a combination of pre-omicron and omicron infection was most protective against BA.2.75 reinfection. Viral immune-system evasion may have accelerated recently to overcome high immunity in the global population, thereby also accelerating the waning of natural immunity.

An essay, also published in the NEJM, strikes an equally cautionary note.4 It is a very interesting history of the Covid pandemic from the beginning. It describes the efficacy of the original vaccines and monoclonal antibodies against initial variants. This efficacy fell with the evolution of the virus and the development of subvariants.

Given the ability to use mRNA technology to respond quickly to variant strains, bivalent vaccines were created to counter this new threat, and released by vaccine manufacturers in January and February 2022. On June 28, 2022, researchers presented data on their bivalent vaccines to the FDA.

The results were underwhelming. Bivalent boosters resulted in levels of neutralizing antibodies against BA.1 that were only 1.5 to 1.75 times as high as those achieved with monovalent boosters. Previous experience with the companies’ vaccines suggested that this difference was unlikely to be clinically significant.

Safety data were reassuring. The author concludes that fortunately, SARS-CoV-2 variants haven’t evolved to resist the protection against severe disease offered by vaccination or previous infection.

If that happens, we will need to create a variant-specific vaccine. Although boosting with a bivalent vaccine is likely to have a similar effect as boosting with a monovalent vaccine, booster dosing is probably best reserved for the people most likely to need protection against severe disease, namely older adults, people with multiple coexisting conditions that put them at high risk for serious illness, and those who are immuno-compromised.

In the meantime, the author recommends that we should stop trying to prevent all symptomatic infections in healthy, young people by boosting them with vaccines containing mRNA from strains that might disappear a few months later.

References:

1. Bobrovitz N et al. Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the omicron variant and severe disease: a systematic review and meta-regression. Lancet Infect Dis 2023. Published Online January 18, 2023. https://doi.org/10.1016/S1473-3099(22)00801-5.
2. Tsz Tsun Lai F et al. Booster vaccination with inactivated wholevirus or mRNA vaccines and COVID-19–related deaths among people with multimorbidity: a cohort study. CMAJ 2023 January 30;195:E143-52. doi: 10.1503/cmaj.221068.
3. Chemaitelly H et al. Protection against Reinfection with the Omicron BA.2.75 Subvariant. published on January 18, 2023, at NEJM.org. doi: 10.1056/NEJMc2214114.
4. Offit P. Bivalent Covid-19 Vaccines — A Cautionary Tale. Published on January 11, 2023, at NEJM.org. doi: 10.1056/NEJMp2215780.

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Diet & Lifestyle
The evidence for long-lasting benefits of a healthy lifestyle continues to mount. A population based, prospective cohort study from China looked at the protective effect of an optimal lifestyle profile against memory loss in older individuals.1 Participants were Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009.

Participants were followed up until death, discontinuation, or December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least seven of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or former smoking, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. The participants numbered 29,072 (mean age of 72.23 years) 48.54 per cent (n=14 113) of which were women.

The authors’ conclusion was that a healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele.

Finally and in brief, healthy eating seems to be good for you. One study looked at the associations of dietary scores for four healthy eating patterns with risk of total and cause-specific mortality.2

It was a prospective cohort study and included initially healthy women from the Nurses’ Health Study (NHS; 1984-2020) and men from the Health Professionals Follow-up Study (HPFS; 1986-2020).

The diets they looked at were Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED score, Healthful Plant-based Diet Index (HPDI), and Alternate Healthy Eating Index (AHEI). The final study sample included 75,230 women from the NHS (mean baseline age, 50.2 years) and 44,085 men from the HPFS (mean baseline age, 53.3 years].

After 36 years of follow-up, greater adherence to various healthy eating patterns was consistently associated with lower risk of total and cause-specific mortality.2

Another study looked at carbohydrate diet, weight loss and blood glucose control.3 The authors evaluated the effect of diets low in energy density (1 kcal/g) and high in either potatoes (Potato) or pulses (Bean) on blood glucose control in participants with insulin resistance.

This was an eight-week randomized, parallel design, controlled feeding study. Compliance with the diets was excellent at 88 per cent and body weight was reduced in both diets (Potato: -5.6 per cent; Bean: -4.1 per cent) with no significant difference between the two diets.

The conclusion was that potato and bean diets low in energy density were equally effective in reducing insulin resistance and promoting weight loss in individuals with impaired blood glucose control.

References:

1. Jia J et al. Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study. BMJ 2023;380:e072691. http://dx.doi.org/10.1136/bmj‑2022‑072691.
2. Shan Z et al. Healthy Eating Patterns and Risk of Total and Cause-Specific Mortality. JAMA Intern Med. doi: 10.1001/jamainternmed.2022.6117. Published online January 9, 2023.
3. Rebello CJ et al. Low-Energy Dense Potato- and Bean-Based Diets Reduce Body Weight and Insulin Resistance: A Randomized, Feeding, Equivalence Trial. J Med Food 2022 Dec;25 (12):1155-1163. doi: 10.1089/jmf.2022.0072. Epub 2022 Nov 11.