The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Cost-effectiveness of a stepwise cardiometabolic disease prevention program: results of a randomized controlled trial in primary care.

BACKGROUND: Cardiometabolic diseases (CMD) are the major cause of death worldwide and are associated with a lower quality of life and high healthcare costs. To prevent a further rise in CMD and related healthcare costs, early detection and adequate management of individuals at risk could be an effective preventive strategy. The objective of this study was to determine long-term cost-effectiveness of stepwise CMD risk assessment followed by individualized treatment if indicated compared to care as usual. A computer-based simulation model was used to project long-term health benefits and cost-effectiveness, assuming the prevention program was implemented in Dutch primary care. METHODS: A randomized controlled trial in a primary care setting in which 1934 participants aged 45-70 years without recorded CMD or CMD risk factors participated. The intervention group was invited for stepwise CMD risk assessment through a risk score (step 1), additional risk assessment at the practice in case of increased risk (step 2) and individualized follow-up treatment if indicated (step 3). The control group was not invited for risk assessment, but completed a health questionnaire. Results of the effectiveness analysis on systolic blood pressure (- 2.26 mmHg; 95% CI - 4.01: - 0.51) and total cholesterol (- 0.15 mmol/l; 95% CI - 0.23: - 0.07) were used in this analysis. Outcome measures were the costs and benefits after 1-year follow-up and long-term (60 years) cost-effectiveness of stepwise CMD risk assessment compared to no assessment. A computer-based simulation model was used that included data on disability weights associated with age and disease outcomes related to CMD. Analyses were performed taking a healthcare perspective. RESULTS: After 1 year, the average costs in the intervention group were 260 Euro higher than in the control group and differences were mainly driven by healthcare costs. No meaningful change was found in EQ 5D-based quality of life between the intervention and control groups after 1-year follow-up (- 0.0154; 95% CI - 0.029: 0.004). After 60 years, cumulative costs of the intervention were 41.4 million Euro and 135 quality-adjusted life years (QALY) were gained. Despite improvements in blood pressure and cholesterol, the intervention was not cost-effective (ICER of 306,000 Euro/QALY after 60 years). Scenario analyses did not allow for a change in conclusions with regard to cost-effectiveness of the intervention. CONCLUSIONS: Implementation of this primary care-based CMD prevention program is not cost-effective in the long term. Implementation of this program in primary care cannot be recommended. TRIAL REGISTRATION: Dutch Trial Register NTR4277 , registered on 26 November 2013.

Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes.

BACKGROUND: Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed. METHODS: A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners' Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated. RESULTS: Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06-1.30) for atrial fibrillation, 1.66 (1.55-1.83) for ischaemic heart disease, and 2.36 (2.10-2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter. CONCLUSION: There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.

Characteristics and motives of non-responders in a stepwise cardiometabolic disease prevention program in primary care.

BACKGROUND: A high response rate is an important condition for effective prevention programs. We aimed at gaining insight into the characteristics and motives of non-responders in different stages of a stepwise prevention program for cardiometabolic diseases (CMD) in primary care. METHODS: We performed a non-response analysis within a randomized controlled trial assessing the effectiveness of a stepwise CMD prevention program in the Netherlands. Patients between 45 and 70 years without known CMD were invited for stage 1 of the program, completing a CMD risk score. Patients with an increased risk were advised to visit their general practice for additional measurements, stage 2 of the program. We analyzed determinants of non-response using data from the risk score, electronic medical records, questionnaires and Statistics Netherlands. RESULTS: Non-response in stage 1 was associated with a younger age, male sex, a migration background, a low prosperity score, self-employment, being single and having lower consultations rates in general practice. Non-response in stage 2 was associated with a low prosperity score, being employed, having no chronic illness, smoking, a normal waist circumference, a negative family history for cardiovascular disease or diabetes and having a lower consultation rate. More than half of the non-responders in stage 2 reported not visiting the GP because they did not expect to have any CMD, despite their increased risk. CONCLUSIONS: To achieve a larger and more equal uptake of prevention programs for CMD, we should use methods adapted to characteristics of non-responders, such as targeted invitation methods and improved risk communication.

Effectiveness of a stepwise cardiometabolic disease prevention program: Results of a randomized controlled trial in primary care.

Effective preventive strategies for cardiometabolic disease (CMD) are needed. We aim to establish the effectiveness of a stepwise CMD risk assessment followed by individualized treatment if indicated compared to care as usual. We conducted a RCT between 2014 and 2017. Individuals (45-70 years) without CMD or CMD risk factors were invited for stepwise CMD risk assessment through a risk score (step1), additional risk assessment at the practice in case of high-risk (step2) and individualized follow-up treatment if indicated (step3). We compared newly detected CMD and newly prescribed drugs during one-year follow-up, and change in CMD risk profile between baseline and one-year follow-up among participants who completed step2 to matched controls. A CMD was diagnosed almost three times more often (OR 2.90, 95% CI 2.25: 3.72) in the intervention compared to the control group, in parallel with newly prescribed antihypertensive and lipid lowering drugs (OR 2.85, 95% CI 1.96: 4.15 and 3.23, 95% CI 2.03: 5.14 respectively). Waist circumference significantly decreased between the intervention compared to the control group (mean -3.08 cm, 95% CI -3.73: -2.43). No differences were observed for changes in BMI and smoking. Systolic blood pressure (mean -2.26 mmHg, 95% CI -4.01: -0.51) and cholesterol ratio (mean -0.11, 95% CI -0.19: -0.02) significantly decreased within intervention participants between baseline and one-year follow-up. In conclusion, implementation of the CMD prevention program resulted in the detection of two- to threefold more patients with CMD. A significant drop in systolic blood pressure and cholesterol levels was found after one year of treatment. Modelling of these results should confirm the effect on long term endpoints. Trial registration: Dutch trial Register number NTR4277.

Proactive screening for symptoms: A simple method to improve early detection of unrecognized cardiovascular disease in primary care. Results from the Lifelines Cohort Study.

Cardiovascular disease (CVD) often goes unrecognized, despite symptoms frequently being present. Proactive screening for symptoms might improve early recognition and prevent disease progression or acute cardiovascular events. We studied the diagnostic value of symptoms for the detection of unrecognized atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) and developed a corresponding screening questionnaire. We included 100,311 participants (mean age 52 ± 9 years, 58% women) from the population-based Lifelines Cohort Study. For each outcome (unrecognized AF/HF/CAD), we built a multivariable model containing demographics and symptoms. These models were combined into one 'three-disease' diagnostic model and questionnaire for all three outcomes. Results were validated in Lifelines participants with chronic obstructive pulmonary disease (COPD) and diabetes mellitus (DM). Unrecognized CVD was identified in 1325 participants (1.3%): AF in 131 (0.1%), HF in 599 (0.6%), and CAD in 687 (0.7%). Added to age, sex, and body mass index, palpitations were independent predictors for unrecognized AF; palpitations, chest pain, dyspnea, exercise intolerance, health-related stress, and self-expected health worsening for unrecognized HF; smoking, chest pain, exercise intolerance, and claudication for unrecognized CAD. Area under the curve for the combined diagnostic model was 0.752 (95% CI 0.737-0.766) in the total population and 0.757 (95% CI 0.734-0.781) in participants with COPD and DM. At the chosen threshold, the questionnaire had low specificity, but high sensitivity. In conclusion, a short questionnaire about demographics and symptoms can improve early detection of CVD and help pre-select people who should or should not undergo further screening for CVD.

Uptake and detection rate of a stepwise cardiometabolic disease detection program in primary care-a cohort study.

BACKGROUND: Early detection and treatment of cardiometabolic diseases (CMD) in high-risk patients is a promising preventive strategy to anticipate the increasing burden of CMD. The Dutch guideline 'the prevention consultation' provides a framework for stepwise CMD risk assessment and detection in primary care. The aim of this study was to assess the outcome of this program in terms of newly diagnosed CMD. METHODS: A cohort study among 30 934 patients, aged 45-70 years without known CMD or CMD risk factors, who were invited for the CMD detection program within 37 general practices. Patients filled out a CMD risk score (step 1), were referred for additional risk profiling in case of high risk (step 2) and received lifestyle advice and (pharmacological) treatment if indicated (step 3). During 1-year follow-up newly diagnosed CMD, prescriptions and abnormal diagnostic tests were assessed. RESULTS: Twelve thousand seven hundred and thirty-eight patients filled out the risk score of which 865, 6665 and 5208 had a low, intermediate and high CMD risk, respectively. One thousand seven hundred and fifty-five high-risk patients consulted the general practitioner, in 346 of whom a new CMD was diagnosed. In an additional 422 patients a new prescription and/or abnormal diagnostic test were found. CONCLUSIONS: Implementation of the CMD detection program resulted in a new CMD diagnosis in one-fifth of high-risk patients who attended the practice for completion of their risk profile. However, the potential yield of the program could be higher given the considerable number of additional risk factors-such as elevated glucose, blood pressure and cholesterol levels-found, requiring active follow-up and presumably treatment in the future.

Feasibility and success rates of response enhancing strategies in a stepwise prevention program for cardiometabolic diseases in primary care.

BACKGROUND: Prevention programs for cardiometabolic diseases (CMD), including cardiovascular disease, diabetes mellitus and chronic kidney disease are feasible, but evidence for the cost-effectiveness of selective CMD prevention programs is lacking. Response rates have an important role in effectiveness, but methods to increase response rates have received insufficient attention. The aim of the current study is to determine the feasibility and the success rate of a variety of response enhancing strategies to increase the participation in a selective prevention program for CMD. METHODS: The INTEGRATE study is a Dutch randomised controlled trial to assess the effectiveness and cost-effectiveness of a stepwise program for CMD prevention. During the INTEGRATE study we developed ten different response enhancing strategies targeted at different stages of non-response and different patient populations and evaluated these in 29 general practices. RESULTS: A face-to-face reminder by the GP increased the response significantly. Digital reminders targeted at patients with an increased CMD risk showed a positive trend towards participation. Sending invitations and reminders by e-mail generated similar response rates, but at lower costs and time investment than the standard way of dissemination. Translated materials, information gatherings at the practice, self-management toolkits, reminders by telephone, information letters, local media attention and SMS text reminders did not increase the response to our program. CONCLUSIONS: Inviting or reminding patients by e-mail or during GPs consultation may enhance response rates in a selective prevention program for CMD. Different response-enhancing strategies have different patient target populations and implementation issues, therefore practice characteristics need to be taken into account when implementing such strategies. TRIAL REGISTRATION: Dutch trial Register number NTR4277 . Registered 26 November 2013.

Selective prevention of cardiometabolic diseases: activities and attitudes of general practitioners across Europe.

Background: Cardiometabolic diseases (CMDs) are the number one cause of death. Selective prevention of CMDs by general practitioners (GPs) could help reduce the burden of CMDs. This measure would entail the identification of individuals at high risk of CMDs-but currently asymptomatic-followed by interventions to reduce their risk. No data were available on the attitude and the extent to which European GPs have incorporated selective CMD prevention into daily practice. Methods: A survey among 575 GPs from the Czech Republic, Denmark, Greece, the Netherlands and Sweden was conducted between September 2016 and January 2017, within the framework of the SPIMEU-project. Results: On average, 71% of GPs invited their patients to attend for CMD risk assessment. Some used an active approach (47%) while others used an opportunistic approach (53%), but these values differed between countries. Most GPs considered selective CMD prevention as useful (82%) and saw it as part of their normal duties (84%). GPs who did find selective prevention useful were more likely to actively invite individuals compared with their counterparts who did not find prevention useful. Most GPs had a disease management programme for individuals with risk factor(s) for cardiovascular disease (71%) or diabetes (86%). Conclusions: Although most GPs considered selective CMD prevention as useful, it was not universally implemented. The biggest challenge was the process of inviting individuals for risk assessment. It is important to tailor the implementation of selective CMD prevention in primary care to the national context, involving stakeholders at different levels.

Design of the ZWOT-CASE study: an observational study on the effectiveness of an integrated programme for cardiovascular risk management compared to usual care in general practice.

BACKGROUND: Cardiovascular diseases (CVD) contribute considerably to mortality and morbidity. Prevention of CVD by lifestyle change and medication is important and needs full attention. In the Netherlands an integrated programme for cardiovascular risk management (CVRM), based on the Chronic Care Model (CCM), has been introduced in primary care in many regions in recent years, but its effects are unknown. In the ZWOT-CASE study we will assess the effect of integrated care for CVRM in the region of Zwolle on two major cardiovascular risk factors: systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-cholesterol) in patients with or at high risk of CVD. METHODS: This study is a pragmatic observational study comparing integrated care for CVRM with usual care among patients aged 40-80 years with CVD (n = 370) or with a high CVD risk (n = 370) within 26 general practices. After 1 yr follow-up, primary outcomes (SBP and LDL-cholesterol level) are measured. Secondary outcomes include lifestyle habits (smoking, dietary habits, alcohol use, physical activity), risk factor awareness, 10-year risk of cardiovascular morbidity or mortality, health care consumption, patient satisfaction and quality of life. CONCLUSION: The ZWOT-CASE study will provide insight in the effects of integrated care for CVRM in general practice in patients with CVD or at high CVD risk. TRIAL REGISTRATION: The ZWOlle Transmural Integrated Care for CArdiovaScular Risk Management Study; ClinicalTrials.gov ; Identifier: NCT03428061; date of registration: 09-02-2018; This study has been retrospectively registered.

Implementation of selective prevention for cardiometabolic diseases; are Dutch general practices adequately prepared?

OBJECTIVE: Current guidelines acknowledge the need for cardiometabolic disease (CMD) prevention and recommend five-yearly screening of a targeted population. In recent years programs for selective CMD-prevention have been developed, but implementation is challenging. The question arises if general practices are adequately prepared. Therefore, the aim of this study is to assess the organizational preparedness of Dutch general practices and the facilitators and barriers for performing CMD-prevention in practices currently implementing selective CMD-prevention. DESIGN: Observational study. SETTING: Dutch primary care. SUBJECTS: General practices. MAIN OUTCOME MEASURES: Organizational characteristics. RESULTS: General practices implementing selective CMD-prevention are more often organized as a group practice (49% vs. 19%, p = .000) and are better organized regarding chronic disease management compared to reference practices. They are motivated for performing CMD-prevention and can be considered as 'frontrunners' of Dutch general practices with respect to their practice organization. The most important reported barriers are a limited availability of staff (59%) and inadequate funding (41%). CONCLUSIONS: The organizational infrastructure of Dutch general practices is considered adequate for performing most steps of selective CMD-prevention. Implementation of prevention programs including easily accessible lifestyle interventions needs attention. All stakeholders involved share the responsibility to realize structural funding for programmed CMD-prevention. Aforementioned conditions should be taken into account with respect to future implementation of selective CMD-prevention. Key Points  There is need for adequate CMD prevention. Little is known about the organization of selective CMD prevention in general practices.  â€¢ The organizational infrastructure of Dutch general practices is adequate for performing most steps of selective CMD prevention.  â€¢ Implementation of selective CMD prevention programs including easily accessible services for lifestyle support should be the focus of attention.  â€¢ Policy makers, health insurance companies and healthcare professionals share the responsibility to realize structural funding for selective CMD prevention.

Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination.

AIMS: To assess the yield of screening for atrial fibrillation (AF) with a hand-held single-lead electrocardiogram (ECG) device during influenza vaccination in primary care in the Netherlands. METHODS AND RESULTS: We used the MyDiagnostick to screen for AF in persons who participated in influenza vaccination sessions of ten Dutch primary care practices. In case of suspected AF detection by the stick, the recorded 1-min ECG registrations were analysed by a cardiologist. We scrutinized electronic medical files of the general practitioners to obtain information about the cases screened. Multivariable logistic regression analysis was performed to predict the relation between patient characteristics and a new screen-detected diagnosis of AF. In total, 3269 persons were screened for AF during the influenza vaccination sessions of 10 general practitioner practices. As a result, 37 (1.1%) new cases of AF were detected. Prior transient ischeamic attack or stroke (OR 6.05; 95%CI 1.93-19.0), and age (OR 1.09 per year; 95% CI 1.05-1.14) were independent predictors for such newly screen-detected AF. Of the 37 screen-detected AF cases, 2.7% had a CHA2DS2-VASc of 0, 18.9% a score of 1, and 78.4% a score of 2 or more. The majority needed oral anticoagulant therapy. CONCLUSIONS: Screening seems feasible with an easy to use single-lead, hand-held ECG device with automatic AF detection during influenza vaccination in primary care and results in a '1-day' yield of 1.1% new cases of AF. TRIAL REGISTRATION CLINICALTRIALSGOV: NCT02006524.

Design of the INTEGRATE study: effectiveness and cost-effectiveness of a cardiometabolic risk assessment and treatment program integrated in primary care.

BACKGROUND: The increasing prevalence of cardiometabolic disease (CMD) in combination with an ageing population is a major public health problem. Early detection and management of individuals at risk for CMD is required to prevent future health problems with associated costs. General practice is the optimal health care setting to accomplish this goal. Prevention programs for identification and treatment of patients with an increased risk for CMD in primary care have been proven feasible. However, the effectiveness and cost-effectiveness have yet to be demonstrated. The 'Personalized Prevention Approach for CardioMetabolic Risk' (PPA CMR) is such a prevention program. The objective of the INTEGRATE study is to investigate the effectiveness and cost-effectiveness of PPA CMR, as well as to establish determinants for participation and compliance. METHODS: The INTEGRATE study is designed as a stepped-wedge randomized controlled trial with a waiting list control group. In approximately 40 general practices, all enlisted patients without CMD aged 45-70 years, are invited to participate in PPA CMR. After an online risk estimation, patients with a score above risk threshold are invited to the GP for additional measurements, detailed risk profiling and tailored treatment of risk factors through medication and/or lifestyle counseling. At baseline and after twelve months of follow-up lifestyle, health and work status of all participants are established with online questionnaires. Additionally after twelve months, we will determine health care utilization, costs of PPA CMR and compliance. Primary endpoints are the number of newly detected patients with CMD and changes in individual risk factors between the intervention and waiting list control group. Medical data will be extracted from the GPs' electronic medical records. In order to assess factors related to participation, we will send questionnaires to non-participants and assess characteristics of participating practices. For all participants, additional demographic characteristics will be available through Statistics Netherlands. DISCUSSION: The INTEGRATE study will provide insight into the effectiveness and cost-effectiveness of PPA CMR as well as determinants for participation and compliance, which represents essential information to guide further large-scale implementation of primary prevention programs for CMD. TRIAL REGISTRATION NUMBER: NTR4277, The Netherlands National Trial Register, 26-11-2013.

Practice visitations in primary care to improve performance of cardiovascular risk management: an observational study.

BACKGROUND: Despite programmatic protocolised care and structured support, considerable variation is observed in completeness of registration and achieving targets of cardiovascular risk management (CVRM) between individual GPs in the Netherlands. AIM: To determine whether completeness of registration and achieved targets of cardiovascular risk factors improves with practice visitation. DESIGN & SETTING: Observational study utilising the care group's database (2016-2019), comparing changes in registration and achieved targets in non-visited practices and visited practices. METHOD: We compared completeness scores of registration and scores of targets achieved before visitation and 1 year after visitation. Data were analysed on patient level and GP level. Separate analyses were performed among GPs who were ranked in the lower 25% of score distributions. RESULTS: We observed no clinically relevant improvements in completeness of registration and targets achieved in 2017, 2018, and 2019 that could be attributed to visitations in the previous year, both on individual patient level and on aggregated level per general practice. In practices ranked in the lower 25% of the distribution, improvements over time were clinically relevant and larger than the overall changes. Yet, these findings were irrespective of the number of practice visitations. CONCLUSION: Practice visitations in our setting did not seem to lead to improvements in practice performance, nor in completeness of registration of risk factors or in reaching predefined target goals for cardiovascular risk factors.

Patient characteristics and reasons for discontinuation in a cardiovascular risk management programme in The Netherlands.

BACKGROUND: Since 2010, an increasing number of patients have participated in a nurse-led integrated cardiovascular risk management programme in the Netherlands. Because it is important to understand which patients discontinue and why, when evaluating the effectiveness of the care programme, the aim was to identify the reasons for discontinuation. METHODS: Electronic health records of 3997 patients enrolled in a nurse-led integrated cardiovascular risk management programme that started on April 1st, 2010, were manually scrutinized for reasons for discontinuation between April 1st, 2010, and April 1st, 2018. In addition to death and moving to a diabetes care programme, we describe 7 different reasons why patients discontinued the programme and compared the patient characteristics of those who discontinued the programme without specific reasons with those who remained in the care programme for 8 years. RESULTS: Between April 1st, 2010, and April 1st, 2018, 1,190 participants (29.8%) discontinued the CVRM care programme, of whom 271 participants died (6.8%) and 195 were transferred to a diabetes care programme (4.9%). The remaining 724 patients (18.1%) participated 5 years before discontinuation. Of these, 67 (9.3%) had a previous cardiovascular event at the start of the programme. In 355 patients, a specific reason for discontinuation was not found. At baseline, these patients less frequently had a history of CVD than those who continued the programme for 8 years (1.7 vs. 22.6%), were younger (62 vs. 67 years), had less registered cardiovascular comorbidity (atrial fibrillation: 1.1 vs. 7.2%; congestive heart failure 0.3 vs. 1.2%; chronic kidney disease 0.0 vs. 4.5%), were more often smokers (13.0% vs. 4.3%) and took blood pressure- and lipid-lowering drugs twice as often. CONCLUSIONS: In our study we observed that participants who discontinued the nurse-led integrated CVRM care programme between 2010 and 2018 without specific reason or on request were younger, without previous CVD, had less cardiovascular comorbidity and were better adjusted to medication. Exploring the patients' reasons for discontinuation can contribute to an individualized approach to prevent or reduce discontinuation.

Comparing the diagnostic considerations between general practitioners with a special interest in cardiovascular disease and those without in patients with symptoms suggestive of heart failure: a vignette study.

BACKGROUND: General practitioners (GPs) specialized in cardiovascular disease (GPSI-CVD) may suspect heart failure (HF) more easily than GPs not specialized in CVD. We assessed whether GPSI-CVD consider investigations aimed at detecting HF more often than other GPs in two clinical scenarios of an older male person with respiratory and suggestive HF symptoms. METHODS: In this vignette study, Dutch GPs evaluated two vignettes. The first involved a 72-year-old man with hypertension and a 30 pack-year smoking history who presented himself with symptoms of a common cold, but also shortness of breath, reduced exercise tolerance, and signs of fluid overload. The second vignette was similar but now the 72-year-old man was known with chronic obstructive pulmonary disease (COPD). GPs could select diagnostic tests from a multiple-choice list with answer options targeted at HF, COPD or exacerbation of COPD, or lower respiratory tract infection. With Pearson Chi-square or Fisher's exact test differences between the two GP groups were assessed regarding the chosen diagnostic tests. RESULTS: Of the 148 participating GPs, 25 were GPSI-CVD and 123 were other GPs. In the first vignette, GPSI-CVD more often considered performing electrocardiography (ECG) than other GPs (64.0% vs. 32.5%, p = 0.003). In the second vignette, GPSI-CVD were more inclined to perform both ECG (36.0% vs. 12.2%, p = 0.003) and natriuretic peptide testing (56.0% vs. 32.5%, p = 0.006). CONCLUSIONS: Most GPs seemed to consider multiple diagnoses, including HF, with GPSI-CVD more likely performing ECG and natriuretic peptide testing in an older male person with both respiratory and suggestive HF symptoms.

Antihypertensive medication classes and risk of incident dementia in primary care patients: a longitudinal cohort study in the Netherlands.

Background: Hypertension is a modifiable risk factor for dementia affecting over 70% of individuals older than 60. Lowering dementia risk through preferential treatment with antihypertensive medication (AHM) classes that are otherwise equivalent in indication could offer a cost-effective, safe, and accessible approach to reducing dementia incidence globally. Certain AHM-classes have been associated with lower dementia risk, potentially attributable to angiotensin-II-receptor (Ang-II) stimulating properties. Previous study results have been inconclusive, possibly due to heterogeneous methodology and limited power. We aimed to comprehensively investigate associations between AHM (sub-)classes and dementia risk using large-scale continuous, real-world prescription and outcome data from primary care. Methods: We used data from three Dutch General Practice Registration Networks. Primary endpoints were clinical diagnosis of incident all-cause dementia and mortality. Using Cox regression analysis with time-dependent covariates, we compared the use of angiotensin-converting enzyme inhibitors (ACEi) to angiotensin receptor blockers (ARBs), beta blockers, calcium channel blockers (CCBs), and diuretics; and Ang-II-stimulating- to Ang-II-inhibiting AHM. Findings: Of 133,355 AHM-using participants, 5877 (4.4%) developed dementia, and 14,079 (10.6%) died during a median follow-up of 7.6 [interquartile range = 4.1-11.0] years. Compared to ACEi, ARBs [HR = 0.86 (95% CI = 0.80-0.92)], beta blockers [HR = 0.81 (95% CI = 0.75-0.87)], CCBs [HR = 0.77 (95% CI = 0.71-0.84)], and diuretics [HR = 0.65 (95% CI = 0.61-0.70)] were associated with significantly lower dementia risks. Regarding competing risk of death, beta blockers [HR = 1.21 (95% CI = 1.15-1.27)] and diuretics [HR = 1.69 (95% CI = 1.60-1.78)] were associated with higher, CCBs with similar, and ARBs with lower [HR = 0.83 (95% CI = 0.80-0.87)] mortality risk. Dementia [HR = 0.88 (95% CI = 0.82-0.95)] and mortality risk [HR = 0.86 (95% CI = 0.82-0.91)] were lower for Ang-II-stimulating versus Ang-II-inhibiting AHM. There were no interactions with sex, diabetes, cardiovascular disease, and number of AHM used. Interpretation: Among patients receiving AHM, ARBs, CCBs, and Ang-II-stimulating AHM were associated with lower dementia risk, without excess mortality explaining these results. Extensive subgroup and sensitivity analyses suggested that confounding by indication did not importantly influence our findings. Dementia risk may be influenced by AHM-classes' angiotensin-II-receptor stimulating properties. An RCT comparing BP treatment with different AHM classes with dementia as outcome is warranted. Funding: Netherlands Organisation for Health, Research and Development (ZonMw); Stoffels-Hornstra Foundation.

Sex differences in the intensity of statin prescriptions at initiation in a primary care setting.

BACKGROUND: Current guidelines for the prevention and management of cardiovascular diseases (CVD) provide similar recommendations for the use of statins in both women and men. In this study, we assessed sex differences in the intensity of statin prescriptions at initiation and in the achievement of treatment targets, among individuals without and with CVD, in a primary care setting. METHODS: Electronic health record data from statin users were extracted from the PHARMO Data Network. Poisson regressions were used to investigate sex differences in statin intensity and in the achievement of treatment targets. Analyses were stratified by age group, disease status and/or CVD risk category. RESULTS: We included 82 714 individuals (46% women) aged 40-99 years old. In both sexes, the proportion of individuals with a dispensed prescription for high-intensity statin at initiation increased between 2011 and 2020. Women were less likely to be prescribed high-intensity statins as compared with men, both in the subgroups without a history of CVD (risk ratio (RR) 0.69 (95% CI: 0.63 to 0.75)) and with CVD (RR 0.77 (95% CI: 0.74 to 0.81)). Women were less likely than men to achieve target levels of low-density lipoprotein cholesterol following statin initiation in the subgroup without CVD (RR 0.98 (95% CI: 0.97 to 1.00)) and with a history of CVD (RR 0.94 (95% CI: 0.89 to 0.98)). CONCLUSION: Compared with men, women were less likely to be prescribed high-intensity statins at initiation and to achieve treatment targets, both in people without and with a history of CVD, and independent of differences in other individual and clinical characteristics.

Sex Differences in the Primary Prevention of Cardiovascular Diseases in a Dutch Primary Care Setting.

Background: Sex differences in the primary prevention of cardiovascular diseases (CVD) have been shown, but the evidence is mixed and fragmented. In this study, we assessed sex differences in cardiovascular risk factors assessment, risk factor levels, treatment, and meeting of treatment targets, within a Dutch primary care setting. Methods: Data were obtained from individuals aged 40 to 70 years old, without prior CVD, registered during the entire year in 2018 at one of the 51 general practices participating in the Julius General Practitioner's Network (JGPN). History of CVD was defined based on the International Classification of Primary Care (ICPC). Linear and Poisson regressions were used to investigate sex differences in risk factor assessment, risk factor levels, treatment, and meeting of treatment targets. Results: We included 83,903 individuals (50% women). With the exception of glycated hemoglobin (HbA1c), all risk factors for CVD were more often measured in women than in men. Lipid measurements and body mass index values were higher in women, while blood pressure (BP) and HbA1c levels were higher in men, along with estimated glomerular filtration rate (eGFR) levels. Among individuals with elevated BP or cholesterol levels, no sex difference was observed in the prescription of antihypertensive medications (RR 1.00, 95% CI: 0.94-1.06) but women were less likely than men to receive lipid-lowering medications (RR 0.87, 95% CI: 0.79-0.95). Among treated individuals, women were more likely than men to meet adequate levels of blood pressure (RR 1.17, 95% CI: 1.09-1.25) and less likely to meet target levels of cholesterol (RR 0.90, 95% CI: 0.83-0.98). Conclusion: While women were more likely to have their CVD risk factors measured, they were less likely to be prescribed lipid-lowering medications and to meet target levels. When treated, men were less likely to achieve adequate blood pressure control.