Cost-effectiveness of Mediterranean diet and physical activity in secondary CVD prevention: results from the UCC-SMART cohort study.

AIMS: The efficacy of a healthy lifestyle in secondary prevention of cardiovascular disease (CVD) is well established and a first-line recommendation in CVD prevention guidelines. The aim of this study was to assess if they are also cost-effective in patients with established CVD. METHODS: A cost-utility analysis (CUA) was performed comparing a combined Mediterranean diet and physical activity intervention to usual care in CVD patients. The CUA had a healthcare perspective and lifetime horizon. Costs and utilities were estimated using a microsimulation on a cohort of 100,000 CVD patients sampled from the UCC-SMART study (N = 8,947, mean age 62 ±8.7 years and 74% male). Cost-effectiveness was expressed as incrementalcost-effectiveness ratio (ICER), incremental net health benefit (INHB) and incremental net monetary benefit (INMB). RESULTS: Mediterranean diet and physical activity yielded 2.0 incremental quality-adjusted life years (QALYs) and cost reductions of €1,236 per person compared to usual care, resulting in an ICER of €-626/QALY (95%CI -1,929 to 2,673). At a willingness-to-pay of €20,000/QALY, INHB was 2.04 (95%CI 0.99-3.58) QALY and INMB was €40,757 (95%CI 19,819-71,605). The interventions remained cost-effective in a wide range of sensitivity analyses, including worst-case scenarios and scenarios with reimbursement for food and physical activity costs. CONCLUSION: In patients with established CVD, a combined Mediterranean diet and physical activity intervention was cost-saving and highly cost-effective compared to usual care. These findings strongly advocate for the incorporation of lifestyle interventions as integral components of care for all CVD patients.

Lifestyle optimization, including physical activity and healthy diet, is a central recommendation for preventing recurrent cardiovascular events. In this study, we assessed if improving physical activity habits and adherence to a heart-healthy Mediterranean diet would also be a cost-effective option. The results were remarkable - following the Mediterranean diet and engaging in physical activity was expected to result in an increase of 2.0 quality-adjusted life years (QALYs, equal to a life year in perfect health) and cost savings. This means that lifestyle optimization in secondary CVD prevention improves population health, while reducing overall health care costs. These findings underscore the importance of implementing lifestyle changes in the care for all individuals with CVD. A health lifestyle is not only effective in improving health but also a prudent financial decision. Key messages  A combined Mediterranean diet and physical activity intervention is expected to result in two additional QALYs and three additional life years free of recurrent cardiovascular events per patient with with established CVDTargeting a healthy lifestyle is expected to lead to costs savings compared to usual care, due to the low costs of the intervention and the high efficacy in preventing recurrent cardiovascular events.Lifestyle optimization in secondary CVD prevention was shown to result in a dominant incremental cost-effectiveness ratio (ICER) of €-626/QALY, which strongly advocates for healthy policy targeted at implementing lifestyle interventions in regular care for CVD patients.

Real-world nudging, pricing, and mobile physical activity coaching was insufficient to improve lifestyle behaviours and cardiometabolic health: the Supreme Nudge parallel cluster-randomised controlled supermarket trial.

BACKGROUND: Context-specific interventions may contribute to sustained behaviour change and improved health outcomes. We evaluated the real-world effects of supermarket nudging and pricing strategies and mobile physical activity coaching on diet quality, food-purchasing behaviour, walking behaviour, and cardiometabolic risk markers. METHODS: This parallel cluster-randomised controlled trial included supermarkets in socially disadvantaged neighbourhoods across the Netherlands with regular shoppers aged 30-80 years. Supermarkets were randomised to receive co-created nudging and pricing strategies promoting healthier purchasing (N = 6) or not (N = 6). Nudges targeted 9% of supermarket products and pricing strategies 3%. Subsequently, participants were individually randomised to a control (step counter app) or intervention arm (step counter and mobile coaching app) to promote walking. The primary outcome was the average change in diet quality (low (0) to high (150)) over all follow-up time points measured with a validated 40-item food frequency questionnaire at baseline and 3, 6, and 12 months. Secondary outcomes included healthier food purchasing (loyalty card-derived), daily step count (step counter app), cardiometabolic risk markers (lipid profile and HbA1c via finger prick, and waist circumference via measuring tape), and supermarket customer satisfaction (questionnaire-based: very unsatisfied (1) to very satisfied (7)), evaluated using linear mixed-models. Healthy supermarket sales (an exploratory outcome) were analysed via controlled interrupted time series analyses. RESULTS: Of 361 participants (162 intervention, 199 control), 73% were female, the average age was 58 (SD 11) years, and 42% were highly educated. Compared to the control arm, the intervention arm showed no statistically significant average changes over time in diet quality (ߠ- 1.1 (95% CI - 3.8 to 1.7)), percentage healthy purchasing (ß 0.7 ( - 2.7 to 4.0)), step count (ߠ- 124.0 (- 723.1 to 475.1), or any of the cardiometabolic risk markers. Participants in the intervention arm scored 0.3 points (0.1 to 0.5) higher on customer satisfaction on average over time. Supermarket-level sales were unaffected (ß - 0.0 (- 0.0 to 0.0)). CONCLUSIONS: Co-created nudging and pricing strategies that predominantly targeted healthy products via nudges were unable to increase healthier food purchases and intake nor improve cardiometabolic health. The mobile coaching intervention did not affect step count. Governmental policy measures are needed to ensure more impactful supermarket modifications that promote healthier purchases. TRIAL REGISTRATION: Dutch Trial Register ID NL7064, 30 May 2018, https://www.onderzoekmetmensen.nl/en/trial/20990.

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis.

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme.

Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

Determinants of Food Choice and Perceptions of Supermarket-Based Nudging Interventions among Adults with Low Socioeconomic Position: The SUPREME NUDGE Project.

Nudging has received ample attention in scientific literature as an environmental strategy to promote healthy diets, and may be effective for reaching populations with low socioeconomic position (SEP). Therefore, the objective of this study was to investigate how the determinants of food choice shape the perceptions regarding supermarket-based nudging strategies among adults with low SEP. We conducted semi-structured interviews among fifteen adults with low SEP using a pre-defined topic list and visual examples of nudges. Interviews were recorded and transcribed verbatim and content analysis was used to analyse the data. The results show that food costs, convenience, healthiness, taste, and habits were frequently mentioned as determinants of food choice. However, the relative importance of these determinants seemed to be context-dependent. Interviewees generally had a positive attitude towards nudges, especially when they were aligned with product preferences, information needs, and beliefs about the food environment. Still, some interviewees also expressed distrust towards nudging strategies, suspecting ulterior motives. We conclude that nudging strategies should target foods which align with product preferences and information needs. However, the suspicion of ulterior motives highlights an important concern which should be considered when implementing supermarket-based nudging strategies.

To what extent do dietary costs explain socio-economic differences in dietary behavior?

BACKGROUND: Low socio-economic position is associated with consumption of lower quality diets, which may be partly explained by the cost of healthier diets. Therefore, we aimed to investigate the mediating role of dietary costs in the association between educational level and diet quality. METHODS: We used cross-sectional data from Dutch older adults (N = 9399) in the EPIC-NL cohort. Participants provided information about their own and their partners' highest attained educational level (as proxy for socio-economic position). Dietary behavior was assessed using a food frequency questionnaire from which we derived two diet-quality scores, including the Dutch Healthy Diet index 2015 (DHD15-index) and the Dietary Approaches to Stop Hypertension (DASH) diet. Dietary cost estimates were based on food price data from food stores, and linked to reported consumption of food items. Multiple regression analyses and bootstrapping were used examine the mediating role of dietary cost in the association between educational level and diet quality. RESULTS: Mean age of participants was 70 (SD: 10) years and 77% were women. Dietary costs significantly mediated the association between educational level and diet quality, except for high versus middle individual educational level and the DHD15-index. Depending on the dietary and educational indicator, dietary costs explained between 2 and 7% of the association between educational level and diet quality. Furthermore, associations were found to be modified by sex and age. For the DHD15-index, mediation effects were only present in females and adults older than 65 years, and for the DASH diet mediation effects were only present in females and strongest amongst adults older than 65 years compared to adults younger than 65 years. CONCLUSION: Dietary costs seems to play a modest role in explaining educational differences in diet quality in an older Dutch population. Further research is needed to investigate which other factors may explain SEP differences in diet quality.

A new selection method to increase the health benefits of CVD prevention strategies.

Background Cardiovascular disease (CVD) prevention is commonly focused on providing individuals at high predicted CVD risk with preventive medication. Whereas CVD risk increases rapidly with age, current risk-based selection of individuals mainly targets the elderly. However, the lifelong (preventable) consequences of CVD events may be larger in younger individuals. The purpose of this paper is to investigate if health benefits from preventive treatment may increase when the selection strategy is further optimised. Methods Data from three Dutch cohorts were combined ( n = 47469, men:women 1:1.92) and classified into subgroups based on age and gender. The Framingham global risk score was used to estimate 10-year CVD risk. The associated lifelong burden of CVD events according to this 10-year CVD risk was expressed as quality-adjusted life years lost. Based on this approach, the additional health benefits from preventive treatment, reducing this 10-year CVD risk, from selecting individuals based on their expected CVD burden rather than their expected CVD risk were estimated. These benefits were expressed as quality-adjusted life years gained over lifetime. Results When using the current selection strategy (10% risk threshold), 32% of the individuals were selected for preventive treatment. When the same proportion was selected based on burden, more younger and fewer older individuals would receive treatment. Across all individuals, the gain in quality-adjusted life years was 217 between the two strategies, over a 10-year time horizon. In addition, when combining the strategies 5% extra eligible individuals were selected resulting in a gain of 628 quality-adjusted life years. Conclusion Improvement of the selection approach of individuals can help to reduce further the CVD burden. Selecting individuals for preventive treatment based on their expected CVD burden will provide more younger and fewer older individuals with treatment, and will reduce the overall CVD burden.

Dietary patterns in relation to disease burden expressed in Disability-Adjusted Life Years.

BACKGROUND: Although diet is related to chronic disease risk and mortality, its association with total disease burden is not clear. OBJECTIVE: We investigated the minimum impact of different dietary patterns on disability-adjusted life years (DALYs) by using individual longitudinal data. DESIGN: A prospective cohort study was conducted in 33,066 healthy men and women aged 20-70 y recruited into the European Prospective Investigation into Cancer and Nutrition-Netherlands study during 1993-1997. We measured adherence to 3 a priori dietary patterns [the modified Mediterranean diet score (mMDS), the WHO-based Healthy Diet Indicator, and the Dutch Healthy Diet index] and 2 a posteriori dietary patterns. Two a posteriori methods were used to extract Western and prudent patterns. Participants were followed until the end of 2007 for the occurrence of and mortality from the most important chronic diseases. The disease burden was expressed in DALYs, which are the sum of Years Lost due to Disability and Years of Life Lost because of premature mortality. The associations between dietary patterns (per SD change in score) and DALYs were estimated by using a 2-part model and adjusted for relevant confounders (sex, age at recruitment, smoking status and intensity, educational level, marital status, job status, energy intake, and physical activity). RESULTS: After an average follow-up of 12.4 y, higher adherence to the mMDS or prudent pattern was most strongly associated with healthy survival; per SD higher adherence to the mMDS or prudent pattern, fewer healthy life years were lost [51 d (-0.14 DALYs; 95% CI: -0.21, -0.08 DALYs) and 58 d (-0.16 DALYs; 95% CI: -0.23, -0.09 DALYs), respectively]. CONCLUSION: In this Dutch study, of various dietary patterns evaluated, higher adherence to the mMDS or prudent dietary pattern was associated with a lower disease burden as assessed by DALYs.

The contribution of diet and lifestyle to socioeconomic inequalities in cardiovascular morbidity and mortality.

BACKGROUND: The role of differences in diet on the relationship between socioeconomic factors and cardiovascular diseases remains unclear. We studied the contribution of diet and other lifestyle factors to the explanation of socioeconomic inequalities in cardiovascular diseases. METHODS: We prospectively examined the incidence of coronary heart disease (CHD) and stroke events amongst 33,106 adults of the EPIC-NL cohort. Education and employment status indicated socioeconomic status. We used Cox proportional models to estimate hazard ratios ((HR (95% confidence intervals)) for the association of socioeconomic factors with CHD and stroke and the contribution of diet and lifestyle. RESULTS: During 12 years of follow-up, 1617 cases of CHD and 531 cases of stroke occurred. The risks of CHD and stroke were higher in lowest (HR=1.98 (1.67;2.35); HR=1.55 (1.15;2.10)) and lower (HR=1.50 (1.29;1.75); HR=1.42 (1.08;1.86)) educated groups than in the highest. Unemployed and retired subjects more often suffered from CHD (HR=1.37 (1.19;1.58); HR=1.20 (1.05;1.37), respectively), but not from stroke, than the employed. Diet and lifestyle, mainly smoking and alcohol, explained more than 70% of the educational differences in CHD and stroke and 65% of employment status variation in CHD. Diet explained more than other lifestyle factors of educational and employment status differences in CHD and stroke (36% to 67% vs. 9% to 27%). CONCLUSION: The socioeconomic distribution of diet, smoking and alcohol consumption largely explained the inequalities in CHD and stroke in the Netherlands. These findings need to be considered when developing policies to reduce socioeconomic inequalities in cardiovascular diseases.

Domains contributing to disability in activities of daily living.

OBJECTIVE: The WHO International Classification of Functioning, Disability, and Health (ICF)-model describes disability in activities of daily living (ADL) as a multifactorial concept. According to this model, ADL disability is influenced by health conditions, body function and structures, environmental and personal factors, and participation. Current research on ADL disability often focuses on one domain and the contribution of multiple domains is not taken into account. The aim was to investigate which domains contribute to ADL disability. DESIGN: Cross-sectional study. SETTING: General community. PARTICIPANTS: A total of 537 middle-aged and older persons. MEASUREMENTS: Health conditions included number of chronic diseases. Body function comprised Mini-Mental State Examination (MMSE), processing speed, memory, grip strength, physical performance score (PPS), physical activity, sensory problems, body mass index (BMI), intra-abdominal fat, and cholesterol/HDL ratio. Body structure included atherosclerosis and bone mineral density. Environmental factors comprised the degree of urbanization. Personal factors included age, sex, education, smoking, self-management abilities, quality of life, anxiety/panic disorders, and depressive symptoms. Associations between candidate predictors and ADL disability, measured on the Katz ADL-scale, were examined by multivariable adjusted logistic regression analysis. Nagelkerke R(2)-statistic was calculated to investigate the contribution of each domain to ADL disability. RESULTS: Number of chronic diseases (domain health condition), MMSE, PPS, physical activity, BMI, intra-abdominal fat (domain body function), atherosclerosis (domain body structure) and sex, education, smoking, quality of life, and depressive symptoms (domain personal factors) were significant predictors of ADL disability. Fifty-seven percent of the variance in ADL disability was explained by the model. For each domain, the explained variance materially decreased after its exclusion, except for environmental factors. CONCLUSION: The present study shows that multiple domains (ie, health condition, body function, body structure, and personal factors) contribute to current ADL disability.

The global burden of diabetes and its complications: an emerging pandemic.

The number of patients with type 2 diabetes is increasing rapidly in both developed and developing countries around the world. The emerging pandemic is driven by the combined effects of population ageing, rising levels of obesity and inactivity, and greater longevity among patients with diabetes that is attributable to improved management. The vascular complications of type 2 diabetes account for the majority of the social and economic burden among patients and society more broadly. This review summarizes the burden of type 2 diabetes, impaired glucose tolerance, and their vascular complications. It is projected that by 2025 there will be 380 million people with type 2 diabetes and 418 million people with impaired glucose tolerance. Diabetes is a major global cause of premature mortality that is widely underestimated, because only a minority of persons with diabetes dies from a cause uniquely related to the condition. Approximately one half of patients with type 2 diabetes die prematurely of a cardiovascular cause and approximately 10% die of renal failure. Global excess mortality attributable to diabetes in adults was estimated to be 3.8 million deaths.

Cognitive function across the life course and the menopausal transition in a British birth cohort.

OBJECTIVE: Despite biological plausibility, relationships between menopause and cognitive function are inconsistent. We investigated whether menopause status and menopause age were associated with general cognitive ability, verbal memory, and visual search speed and concentration in a large cohort of women while considering vasomotor and psychological symptoms, previous childhood and adult measures of cognitive function, lifetime socioeconomic circumstances, educational attainment, lifestyle factors, and chronic diseases. DESIGN: A nationally representative British cohort of 1261 women born in March 1946 and all aged 53 years at cognitive testing, with prospective information on previous cognitive function, menopausal characteristics, and potential confounders. RESULTS: There was only weak evidence of the effect of natural menopause on cognitive function and no evidence of any effects of hormone therapy use or hysterectomy status. There was a trend across the phases of the natural menopausal transition (pre-, peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and search speed and concentration (P = 0.042), with postmenopausal women having the lowest cognitive function, but there was no trend in verbal memory. Variation in vasomotor and psychological symptoms did not explain these trends. In postmenopausal women, there was a positive trend across menopause age for verbal memory (P = 0.004) and a weak positive trend for the National Adult Reading Test (P = 0.052), with women who reached menopause later having higher cognitive function. Previous cognitive function generally explained the associations, which were further weakened by adjusting for socioeconomic and educational confounders. One exception was the association between the natural menopause transition and search speed and concentration, which remained after adjustment for these factors. CONCLUSION: Menopause adversely affects cognitive function, but this effect may be largely explained by premenopausal cognitive function. These findings suggest that common environmental or genetic factors, operating through long-term or lifelong hormonal mechanisms, may influence the timing of natural menopause and lifetime cognitive function.