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Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study

Author/s: 
Carlsson, Lena M.S., Sjöholm, Kajsa, Jacobson, Peter, Andersson-Assarsson, Johanna C., Svensson, Per-Arne, Taube, Magdalena, Carlsson, Björn, Peltonen, Markku

BACKGROUND

Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.

METHODS

We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.

RESULTS

In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.

CONCLUSIONS

Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. 

Keywords 
Life expectancy obesity bariatric surgery

Association Between Plant and Animal Protein Intake and Overall and Cause-Specific Mortality

Author/s: 
Huang, J., Liao, L.M., Weinstein, S.J., Sinha, R., Graubard, B.I., Albanes, D.

Importance: Although emphasis has recently been placed on the importance of high-protein diets to overall health, a comprehensive analysis of long-term cause-specific mortality in association with the intake of plant protein and animal protein has not been reported.

Objective: To examine the associations between overall mortality and cause-specific mortality and plant protein intake.

Design, setting, and participants: This prospective cohort study analyzed data from 416 104 men and women in the US National Institutes of Health-AARP Diet and Health Study from 1995 to 2011. Data were analyzed from October 2018 through April 2020.

Exposures: Validated baseline food frequency questionnaire dietary information, including intake of plant protein and animal protein.

Main outcomes and measures: Hazard ratios and 16-year absolute risk differences for overall mortality and cause-specific mortality.

Results: The final analytic cohort included 237 036 men (57%) and 179 068 women. Their overall median (SD) ages were 62.2 (5.4) years for men and 62.0 (5.4) years for women. Based on 6 009 748 person-years of observation, 77 614 deaths (18.7%; 49 297 men and 28 317 women) were analyzed. Adjusting for several important clinical and other risk factors, greater dietary plant protein intake was associated with reduced overall mortality in both sexes (hazard ratio per 1 SD was 0.95 [95% CI, 0.94-0.97] for men and 0.95 [95% CI, 0.93-0.96] for women; adjusted absolute risk difference per 1 SD was -0.36% [95% CI, -0.48% to -0.25%] for men and -0.33% [95% CI, -0.48% to -0.21%] for women; hazard ratio per 10 g/1000 kcal was 0.88 [95% CI, 0.84-0.91] for men and 0.86 [95% CI, 0.82-0.90] for women; adjusted absolute risk difference per 10 g/1000 kcal was -0.95% [95% CI, -1.3% to -0.68%] for men and -0.86% [95% CI, -1.3% to -0.55%] for women; all P < .001). The association between plant protein intake and overall mortality was similar across the subgroups of smoking status, diabetes, fruit consumption, vitamin supplement use, and self-reported health status. Replacement of 3% energy from animal protein with plant protein was inversely associated with overall mortality (risk decreased 10% in both men and women) and cardiovascular disease mortality (11% lower risk in men and 12% lower risk in women). In particular, the lower overall mortality was attributable primarily to substitution of plant protein for egg protein (24% lower risk in men and 21% lower risk in women) and red meat protein (13% lower risk in men and 15% lower risk in women).

Conclusions and relevance: In this large prospective cohort, higher plant protein intake was associated with small reductions in risk of overall and cardiovascular disease mortality. Our findings provide evidence that dietary modification in choice of protein sources may influence health and longevity.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Reduction in Saturated Fat Intake for Cardiovascular Disease

Author/s: 
Hopper, L., Martin, N., Jimoh, O.F., Kirk, C., Foster, E., Abdelhamid, A.

Abstract

Background: Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein.

Objectives: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials.

Search methods: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019.

Selection criteria: Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available.

Data collection and analysis: Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment.

Main results: We included 15 randomised controlled trials (RCTs) (16 comparisons, ~59,000 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 21% (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.66 to 0.93, 11 trials, 53,300 participants of whom 8% had a cardiovascular event, I² = 65%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 32. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes.

Authors' conclusions: The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

Trial registration: ClinicalTrials.gov NCT00000611 NCT02062424 NCT00692536 NCT01954472NCT01005498 NCT01634841 NCT03354377.

The Unrecognized Prevalence of Primary Aldosteronism

Author/s: 
Brown, JM, Siddiqui, M, Calhoun, DA, Carey, RM, Hopkins, PN, Williams, GH, Vaidya, A

Background:

Primary aldosteronism is a nonsuppressible renin-independent aldosterone production that causes hypertension and cardiovascular disease.

 

Objective:

To characterize the prevalence of nonsuppressible renin-independent aldosterone production, as well as biochemically overt primary aldosteronism, in relation to blood pressure.

 

Design:

Cross-sectional study.

 

Setting:

4 U.S. academic medical centers.

 

Participants:

Participants with normotension (n = 289), stage 1 hypertension (n = 115), stage 2 hypertension (n = 203), and resistant hypertension (n = 408).

 

Measurements:

Participants completed an oral sodium suppression test, regardless of aldosterone or renin levels, as a confirmatory diagnostic for primary aldosteronism and to quantify the magnitude of renin-independent aldosterone production. Urinary aldosterone was measured in participants in high sodium balance with suppressed renin activity. Biochemically overt primary aldosteronism was diagnosed when urinary aldosterone levels were higher than 12 µg/24 h.

 

Results:

Every blood pressure category had a continuum of renin-independent aldosterone production, where greater severity of production was associated with higher blood pressure, kaliuresis, and lower serum potassium levels. Mean adjusted levels of urinary aldosterone were 6.5 µg/24 h (95% CI, 5.2 to 7.7 µg/24 h) in normotension, 7.3 µg/24 h (CI, 5.6 to 8.9 µg/24 h) in stage 1 hypertension, 9.5 µg/24 h (CI, 8.2 to 10.8 µg/24 h) in stage 2 hypertension, and 14.6 µg/24 h (CI, 12.9 to 16.2 µg/24 h) in resistant hypertension; corresponding adjusted prevalence estimates for biochemically overt primary aldosteronism were 11.3% (CI, 5.9% to 16.8%), 15.7% (CI, 8.6% to 22.9%), 21.6% (CI, 16.1% to 27.0%), and 22.0% (CI, 17.2% to 26.8%). The aldosterone–renin ratio had poor sensitivity and negative predictive value for detecting biochemically overt primary aldosteronism.

 

Limitation:

Prevalence estimates rely on arbitrary and conventional thresholds, and the study population may not represent nationwide demographics.

 

Conclusion:

The prevalence of primary aldosteronism is high and largely unrecognized. Beyond this categorical definition of primary aldosteronism, there is a prevalent continuum of renin-independent aldosterone production that parallels the severity of hypertension. These findings redefine the primary aldosteronism syndrome and implicate it in the pathogenesis of “essential” hypertension.

 

Primary Funding Source:

National Institutes of Health.

Keywords 
primary aldosteronism hypertension cardiovascular disease

Aspirin for Primary Atherosclerotic Cardiovascular Disease Prevention as Baseline Risk Increases: A Meta-Regression Analysis

Author/s: 
Nudy, M, Cooper, J, Ghahramani, M, Ruzieh, M, Mandrola, J, Foy, AJ

Background

Aspirin is often prescribed for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) however, recent randomized trials (RCTs) have challenged this practice. Despite this, aspirin is commonly recommended for high risk primary prevention. We tested the hypothesis that aspirin is more efficacious for the primary prevention of ASCVD, as the baseline risk increases.

Methods

RCTs that compared aspirin to control for primary prevention and evaluated ASCVD (composite of myocardial infarction and ischemic stroke) and major bleeding were included. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. A regression analysis was performed using the ASCVD event rate in the control arm of each RCT as the moderator.

Results

Twelve RCTs were identified with 963,829 patient years of follow-up. Aspirin was associated with a reduction in ASCVD (4.7 versus 5.3 events per 1,000 patient years; RR 0.86; 95% CI 0.79-0.92). There was increased major bleeding among aspirin users (2.5 versus 1.8 events per 1000 patient years, RR 1.41 95% CI, 1.29-1.54). Regression analysis found no relationship between the log rate ratio of ASCVD or major bleeding and incidence of ASCVD in the control arm of each RCT.

Conclusion

Aspirin is associated with a reduction in ASCVD when used for primary prevention; however, it is unlikely to be clinically significant given the increase in bleeding. More importantly, aspirin's treatment effect does not increase as ASCVD risk increases as many hypothesize. There is no suggestion from this data that use of aspirin for higher risk primary prevention patients is beneficial.

Keywords 
aspirin primary prevention Atherosclerotic Cardiovascular Disease myocardial infarction Ischemic Stroke Major Bleeding

Tummy Time and Infant Health Outcomes: A Systematic Review

Author/s: 
Hewitt, Lyndel, Kerr, Erin, Stanley, Rebecca, Okley, A.D.

Context: The World Health Organization recommends tummy time for infants because of the benefits of improved motor development and reduced likelihood of plagiocephaly. Because of poor uptake of these recommendations, the association of tummy time with other health outcomes requires further investigation.

Objective: To review existing evidence regarding the association of tummy time with a broad and specific range of infant health outcomes.

Data sources: Electronic databases were searched between June 2018 and April 2019.

Study selection: Peer-reviewed English-language articles were included if they investigated a population of healthy infants (0 to 12 months), using an observational or experimental study design containing an objective or subjective measure of tummy time which examined the association with a health outcome (adiposity, motor development, psychosocial health, cognitive development, fitness, cardiometabolic health, or risks/harms).

Data extraction: Two reviewers independently extracted data and assessed their quality.

Results: Sixteen articles representing 4237 participants from 8 countries were included. Tummy time was positively associated with gross motor and total development, a reduction in the BMI-zscore, prevention of brachycephaly, and the ability to move while prone, supine, crawling, and rolling. An indeterminate association was found for social and cognitive domains, plagiocephaly, walking, standing, and sitting. No association was found for fine motor development and communication.

Limitations: Most studies were observational in design and lacked the robustness of a randomized controlled trial. High selection and performance bias were also present.

Conclusions: These findings guide the prioritization of interventions aimed at assisting parents meet the global and national physical activity guidelines.

Keywords 
tummy time parents benefits

Statin Use Over 65 Years of Age and All-Cause Mortality: A 10-Year Follow-Up of 19 518 People

Author/s: 
Eilat-Tsanani, S., Schonmann, Y., Mor, E.

Abstract

OBJECTIVES

As life expectancy continues to rise, the burden of cardiovascular disease among older people is expected to increase, making cardiovascular prevention in older people an issue of growing interest and public health importance. We aimed to explore the long‐term effects of adherence to statins on mortality and cardiovascular morbidity among older adults.

DESIGN

A historical population‐based cohort study using routinely collected data.

SETTING

Clalit Health Services Northern District.

PARTICIPANTS

We followed members of Clalit Health Services aged 65 years or older who were eligible for primary cardiovascular prevention for a period of 10 years.

MEASUREMENTS

We fitted Cox regression models to assess the association between the adherence to statin therapy and all‐cause mortality and cardiovascular morbidity, adjusting for cardiovascular risk factors and associated morbidity as time‐updated variables.

RESULTS

The analysis included 19 518 older adults followed during 10 years (median = 9.7 y). All‐cause mortality rates were 34% lower among those who had adhered to statin treatment, compared with those who had not (hazard ratio [HR] = .66; 95% confidence interval [CI] = .56‐.79). Adherence to statins was also associated with fewer atherosclerotic cardiovascular disease events (HR = .80; 95% CI = .71‐.81). The benefit of statin use did not diminish among beyond age 75 and was evident for both women and men.

CONCLUSION

Adherence to statins may be associated with reduced mortality and cardiovascular morbidity among older adults, regardless of age and sex. J Am Geriatr Soc 67:2038–2044, 2019

Keywords 
all-cause mortality cardiovascular events hypercholesterolemia older adults primary prevention

Use of anastrozole for breast cancer prevention (IBIS-II): long-term results of a randomised controlled trial

Author/s: 
Cuzick, J, Sestak, I, Forbes, JF, Dowsett, M, Cawthorn, S, Mansel, RE, Loibl, S, Bonanni, B, Evans, DG, Howell, A, IBIS-II Investigators

BACKGROUND:

Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period.

METHODS:

IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer.

FINDINGS:

3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed.

INTERPRETATION:

This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality.

FUNDING:

Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca.

Keywords 
breast cancer anastrozole female

Testosterone Treatment in Adult Men With Age-Related Low Testosterone: A Clinical Guideline From the American College of Physicians

Author/s: 
Qaseem, A., Horwitch, CA, Vijan, S, Etxeandia-Ikobaltzeta, I, Kansagara, D, Clinical Guidelines Committee of the American College of Physicians

DESCRIPTION:

The American College of Physicians (ACP) developed this guideline to provide clinical recommendations based on the current evidence of the benefits and harms of testosterone treatment in adult men with age-related low testosterone. This guideline is endorsed by the American Academy of Family Physicians.

METHODS:

The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the efficacy and safety of testosterone treatment in adult men with age-related low testosterone. Clinical outcomes were evaluated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and included sexual function, physical function, quality of life, energy and vitality, depression, cognition, serious adverse events, major adverse cardiovascular events, and other adverse events.

TARGET AUDIENCE AND PATIENT POPULATION:

The target audience includes all clinicians, and the target patient population includes adult men with age-related low testosterone.

RECOMMENDATION 1A:

ACP suggests that clinicians discuss whether to initiate testosterone treatment in men with age-related low testosterone with sexual dysfunction who want to improve sexual function (conditional recommendation; low-certainty evidence). The discussion should include the potential benefits, harms, costs, and patient's preferences.

RECOMMENDATION 1B:

ACP suggests that clinicians should reevaluate symptoms within 12 months and periodically thereafter. Clinicians should discontinue testosterone treatment in men with age-related low testosterone with sexual dysfunction in whom there is no improvement in sexual function (conditional recommendation; low-certainty evidence).

RECOMMENDATION 1C:

ACP suggests that clinicians consider intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, as costs are considerably lower for the intramuscular formulation and clinical effectiveness and harms are similar.

RECOMMENDATION 2:

ACP suggests that clinicians not initiate testosterone treatment in men with age-related low testosterone to improve energy, vitality, physical function, or cognition (conditional recommendation; low-certainty evidence).

Keywords 
testosterone guidelines age-related testosterone deficiency
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