Assessment and Management of Patients with Obesity and Hypertension in European Society of Hypertension Excellence Centres. A survey from the ESH Working Group on Diabetes and Metabolic Risk Factors.

BACKGROUND: Healthcare providers are faced with an increasing number of patients with obesity and arterial hypertension. Preventing obesity-associated hypertension and appropriately managing patients with established disease are both important. Hence, the aim of our study was to evaluate the clinical care of patients with obesity and hypertension among ESH Excellence Centres (ECs). METHODS: We conducted a cross-sectional, international 30-item survey through e-mails. RESULTS: In total, 70 representatives of ECs participated (78% men) with 66% of them practicing medicine for more than 30 years and working in well-equipped clinics. Most were internists (41%) and cardiologists (37%) and 73% reported training on the management of obese patients with hypertension. A majority weigh their patients (77%) and evaluate patients for sleep disorders (93%). However, only 47% spend more than 5min to advise for lifestyle modification in general, 59% for weight loss, 56% for salt intake and 64% for exercise. Finally, a minority of participants ask patients if they like their body (6%) or about previous attempts to lose weight (28%), evaluate 24h urinary sodium excretion rate (22%) and provide written (15%) or personalized (10%) dietary advices. If the patient suffers also from type 2 diabetes mellitus, 66% switch treatment to GLP1 receptor agonists and 60% to SGLT2 inhibitors. CONCLUSION: Most clinicians in ESH ECs are well educated regarding obesity-associated hypertension, and clinics are sufficiently equipped to manage these patients, as well. However, several deficits were reported regarding efforts to address and implement obesity specific aspects and interventions to improve care in patients with obesity and hypertension.

Hypertension and obesity still remain two of the main cardiovascular risk factors worldwide.There is a need to lower the incidence of obesity-induced hypertension, and to focus on practical guidelines for the evaluation and management of patients with obesity and hypertension.This is a web-based survey to understand the current clinical practices in assessing/managing patients with obesity and hypertension in ESH Excellence Centres.Most clinicians in ESH ECs are well educated regarding obesity-associated hypertension.Clinics are sufficiently equipped to manage these patients.Several deficits were reported regarding efforts to address and implement obesity specific aspects and interventions to improve care in patients with obesity and hypertension.

Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health.

We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects. For example, ethinyl estradiol, a common oral contraceptive, produced characteristic molecular and physiological effects, including increased levels of inflammation and impact on thyroid, cortisol levels, and pulse, that were distinct from other sources of variability observed in our study. In total, this work illustrates the value of combining deep molecular and digital monitoring of human health. A record of this paper's transparent peer review process is included in the supplemental information.

A cell-free high throughput assay for assessment of SARS-CoV-2 neutralizing antibodies.

Highly accurate serological tests are key to assessing the prevalence of SARS-CoV-2 antibodies and the level of immunity in the population. This is important to predict the current and future status of the pandemic. With the recent emergence of new and more infectious SARS-CoV-2 variants, assays allowing for high throughput analysis of antibodies able to neutralize SARS-CoV-2 become even more important. Here, we report the development and validation of a robust, high throughput method, which enables the assessment of antibodies inhibiting the binding between the SARS-CoV-2 spike protein and angiotensin converting enzyme 2 (ACE2). The assay uses recombinantly produced spike-f and ACE2 and is performed in a bead array format, which allows analysis of up to 384 samples in parallel per instrument over seven hours, demanding only one hour of manual handling. The method is compared to a microneutralization assay utilising live SARS-CoV-2 and is shown to deliver highly correlating data. Further, a comparison with a serological method that measures all antibodies recognizing the spike protein shows that this type of assessment provides important insights into the neutralizing efficiency of the antibodies, especially for individuals with low antibody levels. This method can be an important and valuable tool for large-scale assessment of antibody-based neutralization, including neutralization of new spike variants that might emerge.

Multidomain interventions: state-of-the-art and future directions for protocols to implement precision dementia risk reduction. A user manual for Brain Health Services-part 4 of 6.

Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.

Cardiovascular risk assessment in South and Middle-East Asians living in the Western countries.

Nearly a quarter of the world population lives in the South Asian region (India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and the Maldives). Due to rapid demographic and epidemiological transition in these countries, the burden of non-communicable diseases is growing, which is a serious public health concern. Particularly, the prevalence of pre-diabetes, diabetes and atherosclerotic cardiovascular disease (CVD) is increasing. South Asians living in the West have also substantially higher risk of CVD and mortality compared with white Europeans and Americans. Further, as a result of global displacement over the past three decades, Middle-Eastern immigrants now represent the largest group of non-European immigrants in Northern Europe. This vulnerable population has been less studied. Hence, the aim of the present review was to address cardiovascular risk assessment in South Asians (primarily people from India, Pakistan and Bangladesh), and Middle-East Asians living in Western countries compared with whites (Caucasians) and present results from some major intervention studies. A systematic search was conducted in PubMed to identify major cardiovascular health studies of South Asian and Middle-Eastern populations living in the West, relevant for this review. Results indicated an increased risk of CVD. In conclusion, both South Asian and Middle-Eastern populations living in the West carry significantly higher risk of diabetes and CVD compared with native white Europeans. Lifestyle interventions have been shown to have beneficial effects in terms of reduction in the risk of diabetes by increasing insulin sensitivity, weight loss as well as better glycemic and lipid control.

Neighborhood socioeconomic status and aortic stenosis: A Swedish study based on nationwide registries and an echocardiographic screening cohort.

BACKGROUND: Aortic stenosis (AS) is the most common valvular heart disease in developed countries, confers high mortality in advanced cases, but can effectively be reversed using endovascular or open-heart surgery. We evaluated the association between AS and neighborhood socioeconomic status (NSES). METHODS: We used Swedish population-based nationwide registers and an echocardiography screening cohort during the study period 1997-2014. NSES was determined by an established neighborhood deprivation index composed of education, income, unemployment, and receipt of social welfare. Multilevel adjusted logistic regression models determined the association between NSES and incident AS (according to ICD-10 diagnostic codes). RESULTS: The study population of men and women (n=6,641,905) was divided into individuals living in high (n = 1,608,815 [24%]), moderate (n = 3,857,367 [58%]) and low (n = 1,175,723 [18%]) SES neighborhoods. There were 63,227 AS cases in total. Low NSES (versus high) was associated with a slightly increased risk of AS (OR 1.06 [95% CI 1.03-1.08]) in the nationwide study population. In the echocardiography screening cohort (n = 1586), the association between low NSES and AS was markedly stronger (OR: 2.73 [1.05-7.12]). There were more previously undiagnosed AS cases in low compared to high SES neighborhoods (3.1% versus 1.0%). CONCLUSIONS: In this nationwide Swedish register study, low NSES was associated with a slightly increased risk of incident AS. However, the association was markedly stronger in the echocardiography screening cohort, which revealed an almost three-fold increase of AS among individuals living in low SES neighborhoods, possibly indicating an underdiagnosis of AS among these individuals.

PERson-centredness in hypertension management using information technology (PERHIT): a protocol for a randomised controlled trial in primary health care.

Purpose: For primary health care (PHC), hypertension is the number one diagnosis for planned health care visits. The treatment of high blood pressure (BP) and its consequences constitutes a substantial economic burden. In spite of efficient antihypertensive medications, a low percentage of patients reach a well-controlled BP. The PERson-centredness in Hypertension management using Information Technology (PERHIT) Study is a multicentre randomised controlled trial. PERHIT is designed to evaluate the effect of supporting self-management on systolic blood pressure by the use of information technology in Swedish primary health care.Materials and Methods: After inclusion, 900 patients from 36 PHC centres are randomised to two groups. In the intervention group, patients are provided with a self-management support system including a home-BP monitor and further requested to perform self-reports and measure BP every evening for eight consecutive weeks. In the control group, patients receive treatment as usual.Results: The primary outcome will be the change in systolic blood pressure in patients with hypertension. In addition, person-centredness, daily life activities, awareness of risk and health care costs will also be evaluated.Conclusion: The results of this randomised controlled trial with assessment of blood pressure and same-day self-reports will provide patients a tool to understand the interplay between blood pressure and lifestyle applicable to primary health care. The self-management support system may be of importance for improved adherence to treatment and persistence to treatment recommendations.

Modelling the Effect of Compliance with Nordic Nutrition Recommendations on Cardiovascular Disease and Cancer Mortality in the Nordic Countries.

The objective of this study is to estimate the number of deaths attributable to cardiovascular diseases and diet-related cancers that could be prevented or delayed in the Nordic countries, i.e., Sweden, Denmark, Finland, Norway, and Iceland, if adults adhere to the Nordic Nutrition Recommendations (NNR). A sex- and age-group specific epidemiological macro-simulation model was used to estimate the preventable deaths due to the differences between country specific actual intake and recommended intake of changes in food components. Data included in the model are a baseline scenario (actual dietary intake), a counterfactual scenario (recommended intake), and age-and sex-specific mortality for cardiovascular and diet-related cancer diseases, together with the total population risk of a specific year. Monte Carlo analyses with 5000 iterations were performed to produce the 95% uncertainty intervals. The model predicts that Iceland would benefit the most by adhering to the NNR, followed by Finland. In all the Nordic countries, the highest benefit would be achieved by adhering to the fruits and vegetable intakes, except Denmark, where a lower recommended intake of salt would provide the highest benefit. For men, fruits and vegetables could have saved more lives compared to other dietary components for all the Nordic countries, while for women, dietary fiber was the most prominent factor, except in Iceland. The Nordic Council should consider policies for promoting healthy eating according to the needs of each country.

Systematic assessment of antibody selectivity in plasma based on a resource of enrichment profiles.

There is a strong need for procedures that enable context and application dependent validation of antibodies. Here, we applied a magnetic bead assisted workflow and immunoprecipitation mass spectrometry (IP-MS/MS) to assess antibody selectivity for the detection of proteins in human plasma. A resource was built on 414 IP experiments using 157 antibodies (targeting 120 unique proteins) in assays with heat-treated or untreated EDTA plasma. For each protein we determined their antibody related degrees of enrichment using z-scores and their frequencies of identification across all IP assays. Out of 1,313 unique endogenous proteins, 426 proteins (33%) were detected in >20% of IPs, and these background components were mainly comprised of proteins from the complement system. For 45% (70/157) of the tested antibodies, the expected target proteins were enriched (z-score ≥ 3). Among these 70 antibodies, 59 (84%) co-enriched other proteins beside the intended target and mainly due to sequence homology or protein abundance. We also detected protein interactions in plasma, and for IGFBP2 confirmed these using several antibodies and sandwich immunoassays. The protein enrichment data with plasma provide a very useful and yet lacking resource for the assessment of antibody selectivity. Our insights will contribute to a more informed use of affinity reagents for plasma proteomics assays.

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension.

AIMS: Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. METHODS AND RESULTS: Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. CONCLUSION: May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk.

Prevention of Cardiovascular Disease and Cancer Mortality by Achieving Healthy Dietary Goals for the Swedish Population: A Macro-Simulation Modelling Study.

The objective is to estimate the number of deaths attributable to cardiovascular diseases and diet-related cancers that could be prevented or delayed in Sweden if adults adhere to the official dietary recommendations. We used an age-group and sex-specific epidemiological macro-simulation model to estimate preventable deaths due to the discrepancies between actual intake and recommended intake of changes in food components. Data included in the model are a baseline scenario (actual dietary intake), a counterfactual scenario (recommended intake) and age- and sex-specific mortality for cardiovascular and diet-related cancer diseases together compared with the total population risk of a specific year. Monte Carlo analyses with 5000 iterations was performed to produce the 95% uncertainty intervals (UI). The model predicts that 6405 (95% UI: 5086⁻7086) deaths could be prevented or delayed if the Swedish population could adhere to official dietary recommendations in a year. More deaths would be saved for men than women. The recommendations for fruits and vegetables could have saved 47% of the deaths, followed by fiber intake (32%). For men, fruits and vegetables could have saved more compared to other dietary components, while for women dietary fiber was the prominent factor. Public health policies should consider ensuring healthy eating practices for the Swedish population.

High-Density Antigen Microarrays for the Assessment of Antibody Selectivity and Off-Target Binding.

With the increasing availability of collections of antibodies, their evaluation in terms of binding selectivity becomes an important but challenging task. Planar antigen microarrays are very suitable tools to address this task and provide a powerful proteomics platform for the characterization of the binding selectivity of antibodies toward thousands of antigens in parallel. In this chapter, we describe our in-house developed procedures for the generation of high-density planar antigen microarrays with over 21,000 features. We also provide the details of the assay protocol, which we routinely use for the assessment of binding selectivity of the polyclonal antibodies generated within the Human Protein Atlas.

Multiplexed Antigen Bead Arrays for the Assessment of Antibody Selectivity and Epitope Mapping.

With the increasing number of binding reagents for affinity-based investigations of the human proteome, high-throughput tools for the characterization of the used reagents become essential. For the analysis of binding selectivity, bead-based antigen arrays offer a miniaturized and parallelized assay platform to meet such needs, as they enable two-dimensional multiplexing to analyze up to 384 samples against up to 500 analytes in a single round of analysis. In this chapter, we describe our protocols for the generation of multiplex bead arrays built on immobilized protein fragments, as well as biotinylated peptides. Combined together, these two versions of antigen arrays offer a versatile approach for multiplexed characterization of antibody binding selectivity, off-target interactions, as well as mapping for the amino acids of epitopes involved in antibody binding.

The Montreal Cognitive Assessment: Normative Data from a Large Swedish Population-Based Cohort.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) has a high sensitivity for detecting cognitive dysfunction. Swedish normative data does not exist and international norms are often derived from populations where cognitive impairment has not been screened for and not been thoroughly assessed to exclude subjects with dementia or mild cognitive impairment. OBJECTIVE: To establish norms for MoCA and develop a regression-based norm calculator based on a large, well-examined cohort. METHODS: MoCA was administered on 860 randomly selected elderly people from a population-based cohort from the EPIC study. Cognitive dysfunction was screened for and further assessed at a memory clinic. After excluding cognitively impaired participants, normative data was derived from 758 people, aged 65-85. RESULTS: MoCA cut-offs (-1 to -2 standard deviations) for cognitive impairment ranged from <25 to <21 for the lowest educated and <26 to <24 for the highest educated, depending on age group. Significant predictors for MoCA score were age, sex and level of education. CONCLUSION: We present detailed normative MoCA data and cut-offs according to the DSM-5 criteria for cognitive impairment based on a large population-based cohort of elderly individuals, screened and thoroughly investigated to rule out cognitive impairment. Level of education, sex, and age should be taken in account when evaluating MoCA score, which is facilitated by our online regression-based calculator that provide percentile and z-score for a subject's MoCA score.

Weight change patterns and healthcare costs in patients with newly-diagnosed type-2 diabetes in Sweden.

AIMS: To describe weight-change pathways in patients with type 2 diabetes (T2D) and associated healthcare costs using repeated BMI measurements and healthcare utilization data. METHODS: Patients with newly-diagnosed T2D with body mass index (BMI, kg/m2) at diagnosis and subsequent measures at year 1-3 were identified. Based on three-year BMI change, patients were assigned to one of 27 BMI change pathways defined by annual BMI change: BMI↗ (≥1 BMI unit increase), BMI→ (<1 BMI unit change), and BMI↘ (≥1 BMI unit decrease). Mean annual and three-year cumulative healthcare costs were estimated for each pathway by combining Swedish unit costs with resource use from primary care and national patient registers. RESULTS: Cohort consisted of 15,819 patients; 44% women, mean age of 61 years, HbA1c of 6.7% (50mmol/mol), BMI of 30.6kg/m2. Most common BMI pathways (mean costs): BMI→→→ (€5,311), BMI↘→→ (€5,461), and BMI→→↘ (€6,281). General trends: BMI→→→ linked to lowest, BMI↗→↗ linked to highest costs. CONCLUSION: In patients with newly-diagnosed T2D, weight stability was the most common BMI change pattern over 3 years and associated with lowest healthcare costs. Relationship between weight change and healthcare costs appears complex warranting further investigation.

Economic Burden of Obesity: A Systematic Literature Review.

Background: The rising prevalence of obesity represents an important public health issue. An assessment of its costs may be useful in providing recommendations for policy and decision makers. This systematic review aimed to assess the economic burden of obesity and to identify, measure and describe the different obesity-related diseases included in the selected studies. Methods: A systematic literature search of studies in the English language was carried out in Medline (PubMed) and Web of Science databases to select cost-of-illness studies calculating the cost of obesity in a study population aged ≥18 years with obesity, as defined by a body mass index of ≥30 kg/m², for the whole selected country. The time frame for the analysis was January 2011 to September 2016. Results: The included twenty three studies reported a substantial economic burden of obesity in both developed and developing countries. There was considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives. This prevents an informative comparison between most of the studies. Specifically, there was great variety in the included obesity-related diseases and complications among the studies. Conclusions: There is an urgent need for public health measures to prevent obesity in order to save societal resources. Moreover, international consensus is required on standardized methods to calculate the cost of obesity to improve homogeneity and comparability. This aspect should also be considered when including obesity-related diseases.

Increased healthcare utilization costs following initiation of insulin treatment in type 2 diabetes: A long-term follow-up in clinical practice.

AIMS: To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. METHODS: Patients newly initiated on insulin (n=2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. RESULTS: The total mean annual healthcare cost increased from €1656 per patient 2 years before insulin initiation to €3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was €13,823 in the insulin group compared to €9989 in the NIAD group. CONCLUSIONS: Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line.

Economic burden of obesity: a systematic literature review

Background: The rising prevalence of obesity represents an important public health issue. An assessment of its costs may be useful in providing recommendations for policy and decision makers. This systematic review aimed to assess the economic burden of obesity and to identify, measure and describe the different obesity-related diseases included in the selected studies. Methods: A systematic literature search of studies in the English language was carried out in Medline (PubMed) and Web of Science databases to select cost-of-illness studies calculating the cost of obesity in a study population aged ≥18 years with obesity, as defined by a body mass index of ≥30 kg/m², for the whole selected country. The time frame for the analysis was January 2011 to September 2016. Results: The included twenty three studies reported a substantial economic burden of obesity in both developed and developing countries. There was considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives. This prevents an informative comparison between most of the studies. Specifically, there was great variety in the included obesity-related diseases and complications among the studies. Conclusions: There is an urgent need for public health measures to prevent obesity in order to save societal resources. Moreover, international consensus is required on standardized methods to calculate the cost of obesity to improve homogeneity and comparability. This aspect should also be considered when including obesity-related diseases.(AU)