Extreme diurnal temperature range and cardiovascular emergency hospitalisations in a Mediterranean region.

OBJECTIVES: The impact of extreme diurnal temperature range (DTR) on cardiovascular morbidity in Mediterranean regions remains uncertain. We aimed to analyse the impact of extreme low DTR (stable temperature) or high DTR (changeable temperature) on cardiovascular hospitalisations in Catalonia (Southern Europe). METHODS: We conducted a self-controlled case series study using whole-year data from the System for the Development of Research in Primary Care database and 153 weather stations from the Catalan Meteorological Service. The outcome was first emergency hospitalisation. Monthly DTR percentiles were used to define extreme DTR as low (DTR 95th percentile). We assessed two effects: same-day (1-day exposure, coinciding with the extreme DTR episode) and cumulative (3-day exposure, adding two subsequent days). Incidence rate ratios (IRR) were calculated adjusted by age, season and air pollution. Stratified analyses by gender, age or cardiovascular type and regions are provided. RESULTS: We computed 121 206 cardiovascular hospitalisations from 2006 to 2013. The IRR was 1.032 (95% CI 1.005 to 1.061) for same day and 1.024 (95% CI 1.006 to 1.042) for cumulative effects of extreme high DTR. The impact was significant for stroke and heart failure, but not for coronary heart disease. Conversely, extreme low DTR did not increase cardiovascular hospitalisations. CONCLUSIONS: Extreme high DTR increased the incidence of cardiovascular hospitalisations, but not extreme low DTR. Same-day effects of extreme high DTR were stronger than cumulative effects. These findings contribute to better understand the impact of outdoor temperature on health, and to help defining public health strategies to mitigate such impact.

Is it time to use real-world data from primary care in Alzheimer's disease?

BACKGROUND: The analysis of real-world data in clinical research is rising, but its use to study dementia subtypes has been hardly addressed. We hypothesized that real-world data might be a powerful tool to update AD epidemiology at a lower cost than face-to-face studies, to estimate the prevalence and incidence rates of AD in Catalonia (Southern Europe), and to assess the adequacy of real-world data routinely collected in primary care settings for epidemiological research on AD. METHODS: We obtained data from the System for the Development of Research in Primary Care (SIDIAP) database, which contains anonymized information of > 80% of the Catalan population. We estimated crude and standardized incidence rates and prevalences (95% confidence intervals (CI)) of AD in people aged at least 65 years living in Catalonia in 2016. RESULTS: Age- and sex-standardized prevalence and incidence rate of AD were 3.1% (95%CI 2.7-3.6) and 4.2 per 1000 person-years (95%CI 3.8-4.6), respectively. Prevalence and incidence were higher in women and in the oldest people. CONCLUSIONS: Our incidence and prevalence estimations were slightly lower than the recent face-to-face studies conducted in Spain and higher than other analyses of electronic health data from other European populations. Real-world data routinely collected in primary care settings could be a powerful tool to study the epidemiology of AD.

Levels of ankle-brachial index and the risk of diabetes mellitus complications.

OBJECTIVE: We sought to compare the association of categorized ankle-brachial index (ABI) with mortality and complications of diabetes in persons with no symptoms of peripheral arterial disease (PAD) and in primary cardiovascular disease prevention. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of persons with type 2 diabetes aged 35-85 years, from 2006 to 2011. Data were obtained from the Sistema d'Informació per al Desenvolupament de la Investigació en Atenció Primària (SIDIAPQ). Participants had an ABI measurement that was classified into six categories. For each category of ABI, we assessed the incidence of mortality; macrovascular complications of diabetes: acute myocardial infarction (AMI), ischemic stroke, and a composite of these two; and microvascular complications of this metabolic condition: nephropathy, retinopathy, and neuropathy. We also estimated the HRs for these outcomes by ABI category using Cox proportional hazards models. RESULTS: Data from 34 689 persons with type 2 diabetes were included. The mean age was 66.2; 51.5% were men; and the median follow-up was 6.0 years. The outcome with the highest incidence was nephropathy, with 24.4 cases per 1000 person-years in the reference category of 1.1≤ABI≤1.3. The incidences in this category for mortality and AMI were 15.4 and 4.1, respectively. In the Cox models, low ABI was associated with increased risk and was significant from ABI lower than 0.9; below this level, the risk kept increasing steeply. High ABI (over 1.3) was also associated with significant increased risk for most outcomes. CONCLUSIONS: The studied categories of ABI were associated with different risks of type 2 diabetes complications in persons asymptomatic for PAD, who were in primary cardiovascular prevention. These findings could be useful to optimize preventive interventions according to the ABI category in this population.

How well can electronic health records from primary care identify Alzheimer's disease cases?

BACKGROUND: Electronic health records (EHR) from primary care are emerging in Alzheimer's disease (AD) research, but their accuracy is a concern. We aimed to validate AD diagnoses from primary care using additional information provided by general practitioners (GPs), and a register of dementias. PATIENTS AND METHODS: This retrospective observational study obtained data from the System for the Development of Research in Primary Care (SIDIAP). Three algorithms combined International Statistical Classification of Diseases (ICD-10) and Anatomical Therapeutic Chemical codes to identify AD cases in SIDIAP. GPs evaluated dementia diagnoses by means of an online survey. We linked data from the Register of Dementias of Girona and from SIDIAP. We estimated the positive predictive value (PPV) and sensitivity and provided results stratified by age, sex and severity. RESULTS: Using survey data from the GPs, PPV of AD diagnosis was 89.8% (95% CI: 84.7-94.9). Using the dataset linkage, PPV was 74.8 (95% CI: 73.1-76.4) for algorithm A1 (AD diagnoses), and 72.3 (95% CI: 70.7-73.9) for algorithm A3 (diagnosed or treated patients without previous conditions); sensitivity was 71.4 (95% CI: 69.6-73.0) and 83.3 (95% CI: 81.8-84.6) for algorithms A1 (AD diagnoses) and A3, respectively. Stratified results did not differ by age, but PPV and sensitivity estimates decreased amongst men and severe patients, respectively. CONCLUSIONS: PPV estimates differed depending on the gold standard. The development of algorithms integrating diagnoses and treatment of dementia improved the AD case ascertainment. PPV and sensitivity estimates were high and indicated that AD codes recorded in a large primary care database were sufficiently accurate for research purposes.

Effectiveness of Statins as Primary Prevention in People With Gout: A Population-Based Cohort Study.

BACKGROUND: Cardiovascular guidelines do not give firm recommendations on statin therapy in patients with gout because evidence is lacking. AIM: To analyze the effectiveness of statin therapy in primary prevention of coronary heart disease (CHD), ischemic stroke (IS), and all-cause mortality in a population with gout. METHODS: A retrospective cohort study (July 2006 to December 2017) based on Information System for the Development of Research in Primary Care (SIDIAPQ), a research-quality database of electronic medical records, included primary care patients (aged 35-85 years) without previous cardiovascular disease (CVD). Participants were categorized as nonusers or new users of statins (defined as receiving statins for the first time during the study period). Index date was first statin invoicing for new users and randomly assigned to nonusers. The groups were compared for the incidence of CHD, IS, and all-cause mortality, using Cox proportional hazards modeling adjusted for propensity score. RESULTS: Between July 2006 and December 2008, 8018 individuals were included; 736 (9.1%) were new users of statins. Median follow-up was 9.8 years. Crude incidence of CHD was 8.16 (95% confidence interval [CI]: 6.25-10.65) and 6.56 (95% CI: 5.85-7.36) events per 1000 person-years in new users and nonusers, respectively. Hazard ratios were 0.84 (95% CI: 0.60-1.19) for CHD, 0.68 (0.44-1.05) for IS, and 0.87 (0.67-1.12) for all-cause mortality. Hazard for diabetes was 1.27 (0.99-1.63). CONCLUSIONS: Statin therapy was not associated with a clinically significant decrease in CHD. Despite higher risk of CVD in gout populations compared to general population, patients with gout from a primary prevention population with a low-to-intermediate incidence of CHD should be evaluated according to their cardiovascular risk assessment, lifestyle recommendations, and preferences, in line with recent European League Against Rheumatism recommendations.

Role of Low Ankle-Brachial Index in Cardiovascular and Mortality Risk Compared with Major Risk Conditions.

Cardiovascular prevention is of particular interest in persons with asymptomatic peripheral arterial disease. We aimed to quantify its association with mortality and cardiovascular outcomes, compared to other indicators of high risk. We performed a retrospective cohort study using the Database of the Catalan primary care system (SIDIAPQ), for 2006-2015, including 35-85-year-old patients with an ankle-brachial index (ABI) measurement, classified according to the presence of diabetes, cardiovascular disease, and low ABI (<0.9). We calculated the incidences and hazard ratios (HRs) for all-cause mortality, acute myocardial infarction, and ischemic stroke. During a median follow-up of 5.9 years, we analyzed 58,118 persons. The mean (SD) age was 66.6 (10.7) years and 53.4% were men. Compared to the reference group with no diabetes, no previous cardiovascular disease, and normal ankle-brachial index, the HR for all-cause mortality was 1.42 (1.25-1.63) in the group with low ABI, 1.35 (1.26-1.45) in those with diabetes, 1.50 (1.34-1.69) in those with previous cardiovascular disease, and 1.84 (1.68-2.01) in those with low ABI and diabetes. In conclusion, participants with low ABI showed increased mortality, acute myocardial infarction, and ischemic stroke incidence in all the subgroups. Patients with low ankle-brachial index plus diabetes presented increased mortality, acute myocardial infarction, and ischemic stroke risk, all at rates similar to those with previous cardiovascular disease.

Epidemiology of dementia: prevalence and incidence estimates using validated electronic health records from primary care.

PURPOSE: Updated estimates of incidence and prevalence of dementia are crucial to ensure adequate public health policy. However, most of the epidemiological studies in the population in Spain were conducted before 2010. This study assessed the validity of dementia diagnoses recorded in electronic health records contained in a large primary-care database to determine if they could be used for research purposes. Then, to update the epidemiology of dementia in Catalonia (Spain), we estimated crude and standardized prevalence and incidence rates of dementia in Catalonia in 2016. METHODS: The System for the Development of Research in Primary Care (SIDIAP) database contains anonymized information for >80% of the Catalan population. Validity of dementia codes in SIDIAP was assessed in patients at least 40 years old by asking general practitioners for additional evidence to support the diagnosis. Crude and standardized incidence and prevalence (95% CI) in people aged ≥65 years were estimated assuming a Poisson distribution. RESULTS: The positive predictive value of dementia diagnoses recorded in SIDIAP was estimated as 91.0% (95% CI 87.5%-94.5%). Age-and sex-standardized incidence and prevalence of dementia were 8.6/1,000 person-years (95% CI 8.0-9.3) and 5.1% (95% CI 4.5%-5.7%), respectively. CONCLUSION: SIDIAP contains valid dementia records. We observed incidence and prevalence estimations similar to recent face-to-face studies conducted in Spain and higher than studies using electronic health data from other European populations.

Hypertension and high ankle brachial index: the overlooked combination.

OBJECTIVE: Assessment of asymptomatic organ damage in the management of hypertension includes low (<0.9) ankle brachial index (ABI) values. No recommendations are given for patients with high ABI (≥1.3), despite evidence of an association with increased risk. We aimed to study the association of high ABI with all-cause mortality and cardiovascular outcomes in a hypertensive population. METHODS: In anonymized clinical records from the Catalan Primary Care (SIDIAP) database, we designed a large cohort of hypertensive patients aged 35-85 years at the start date. Participants were excluded if they had previous heart failure, coronary heart disease, stroke, diabetes mellitus, or chronic kidney disease. The study population was categorized according to ABI values. Cox proportional hazards models were used to assess all-cause mortality, heart failure, acute myocardial infarction, and stroke. RESULTS: From 2006 through 2015, SIDIAP records included 44 657 hypertensive patients with an ABI measurement 9126 of whom met inclusion criteria. The median follow-up (first to third quartiles) was 6.0 years (4.7-7.6). High ABI (≥ 1.3) was associated with an increase in mortality risk, hazard ratio, and 95% confidence interval: 1.44 (1.10-1.88), similar to the group with ABI at least 0.9 and less than 1.1, hazard ratio 1.36 (1.12-1.65), and lower than all groups with ABI less than 0.9. High ABI values tended to associate with heart failure, hazard ratio 1.34 (0.95-1.91), but the relation of high ABI with acute myocardial infarction and stroke was nonsignificant, hazard ratios 1.30 (0.72-2.35) and 0.97 (0.65-1.42), respectively. CONCLUSION: Patients with high ABI values and hypertension presented an increased all-cause mortality risk that could be considered when advising such patients.

Statins and new-onset atrial fibrillation in a cohort of patients with hypertension. Analysis of electronic health records, 2006-2015.

Hypertension is the most prevalent risk factor for new-onset atrial fibrillation (AF). But few studies have addressed the effect of statins on the incidence of this arrhythmia in patients with hypertension. This study aimed to evaluate the effect of statins on new-onset of this arrhythmia in a hypertensive population, accounting for AF risk. Data from the Information System for the Development of Research in Primary Care was used to recruit a retrospective cohort of ≥55-year-old hypertensive individuals with no ischemic vascular disease, in 2006-2007, followed up through 2015. The effect of initiating statin treatment on new-onset atrial fibrillation was assessed with Cox proportional hazards models adjusted by the propensity score of receiving statin treatment, in the overall study population and stratified by AF risk. Of 100 276 included participants, 9814 initiated statin treatment. The AF incidence per 1000 person-years (95% confidence interval) was 12.5 (12.3-12.8). Statin use associated with a significant (9%) reduction in AF incidence. Differences in absolute AF incidence were higher in the highest AF risk subgroup, and the estimated number needed to treat to avoid one case was 720. The relative effect was poor, similar across groups, and non-significant, as was the association of statins with adverse effects. We found a limited protective effect of statins over new-onset AF in this hypertensive population with no ischemic vascular disease. If there is no further indication, hypertensive patients would not benefit from statin use solely for AF primary prevention.

Effects of extreme temperatures on cardiovascular emergency hospitalizations in a Mediterranean region: a self-controlled case series study.

BACKGROUND: Cold spells and heatwaves increase mortality. However little is known about the effect of heatwaves or cold spells on cardiovascular morbidity. This study aims to assess the effect of cold spells and heatwaves on cardiovascular diseases in a Mediterranean region (Catalonia, Southern Europe). METHODS: We conducted a population-based retrospective study. Data were obtained from the System for the Development of Research in Primary Care and from the Catalan Meteorological Service. The outcome was first emergency hospitalizations due to coronary heart disease, stroke, or heart failure. Exposures were: cold spells; cold spells and 3 or 7 subsequent days; and heatwaves. Incidence rate ratios (IRR) and 95% confidence intervals were calculated using the self-controlled case series method. We accounted for age, time trends, and air pollutants; results were shown by age groups, gender or cardiovascular event type. RESULTS: There were 22,611 cardiovascular hospitalizations in winter and 17,017 in summer between 2006 and 2013. The overall incidence of cardiovascular hospitalizations significantly increased during cold spells (IRR = 1.120; CI 95%: 1.10-1.30) and the effect was even stronger in the 7 days subsequent to the cold spell (IRR = 1.29; CI 95%: 1.22-1.36). Conversely, cardiovascular hospitalizations did not increase during heatwaves, neither in the overall nor in the stratified analysis. CONCLUSIONS: Cold spells but not heatwaves, increased the incidence of emergency cardiovascular hospitalizations in Catalonia. The effect of cold spells was greater when including the 7 subsequent days. Such knowledge might be useful to develop strategies to reduce the impact of extreme temperature episodes on human health.

Role of renal function in cardiovascular risk assessment: A retrospective cohort study in a population with low incidence of coronary heart disease.

BACKGROUND: Early-stage chronic kidney disease (CKD), a marker of cardiovascular risk, is susceptible to therapeutic intervention but need further study in populations with low incidence of coronary heart disease (CHD). Incorporating glomerular filtration rate (GFR) could improve cardiovascular risk prediction in these patients. OBJECTIVE: To determine if decreased GFR is associated with increased risk of cardiovascular morbidity and all-cause mortality and to analyse GFR effect on cardiovascular risk prediction in a population with low CHD incidence. METHODS: Retrospective, observational, population-based study of 1,081,865 adults (35-74years old). Main exposure variable: GFR. OUTCOMES: CHD, cerebrovascular disease, cardiovascular diseases, all-cause mortality. Association between GFR categories of CKD (G1-G5) and outcomes was tested with Cox survival models. G1 was defined as the reference category. Predictive value of GFR was evaluated by integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices. RESULTS: Beginning at stage-3a CKD, increased risk was observed for coronary (HR 1.27 (95%CI 1.14-1.43)), cerebrovascular (HR 1.19 (95%CI 1.06-1.34)), cardiovascular (HR 1.23 (95%CI 1.13-1.34)) and all-cause mortality risk (HR 1.17 (95%CI 1.07-1.27)). GFR did not increase discrimination and reclassification indices significantly for any outcome. CONCLUSION: In general population with low CHD incidence and stage-3 CKD, impaired GFR was associated with increased risk of all cardiovascular diseases studied and all-cause mortality, but adding GFR values did not improve cardiovascular risk calculation. Despite a four-fold higher rate of CHD incidence at GFR G3a compared to G1, this represents moderate cardiovascular risk in our context.

Diabetes and new-onset atrial fibrillation in a hypertensive population.

AIM: The association of diabetes with new-onset atrial fibrillation (AF) remains controversial. Hypertension may partly explain the risk association ascribed to diabetes. We studied the role and characteristics of diabetes in hypertensive patients with no ischemic vascular disease. METHODS: Records of 262,892 persons from the Information System for the Development of Research in Primary Care in Catalonia (Spain) were examined from July 2006 to December 2011. Included participants were ≥55-years-old and hypertensive with no ischemic heart disease, stroke, or peripheral artery disease. We used Cox proportional hazards regression to model incidences in the diabetic and non-diabetic subgroups of our population, and among diabetic patients, diabetes duration and pharmacological treatment, hemoglobin A1C, and body mass index. RESULTS: New-onset AF incidence in diabetic patients was 13.3 per 1000 person-years (mean follow-up: 4.3 years). In non-diabetic patients, it was 10.4 per 1000 person-years (mean follow-up: 4.1 years). Diabetes hazard ratio (HR) for new-onset AF was 1.11 (95% confidence interval (CI): 1.06-1.16). Diabetic patients also diagnosed with obesity had an HR of 1.41 (95% CI: 1.22-1.64). CONCLUSION: Diabetes was modestly associated with new-onset AF in hypertensive patients with no ischemic vascular disease. Among diabetic patients, only obesity reached significance in its association with this arrhythmia.

Incident atrial fibrillation hazard in hypertensive population: a risk function from and for clinical practice.

Determining the risk of atrial fibrillation within the hypertensive population without ischemic vascular disease would aid in decision making on preventive approaches. Accordingly, we aimed to estimate the risk of incident atrial fibrillation in this population. We conducted an historical cohort study between July 1, 2006, and December 31, 2011, using anonymized longitudinal patient information from primary care and hospital discharge records contained in the System for the Development of Research in Primary Care database. We included 255 440 hypertensive patients, aged ≥55 years at the time of study entry. Individuals with previous atrial fibrillation, ischemic heart disease, stroke, and peripheral artery disease were excluded. To build the incident atrial fibrillation risk function, a derivation and a validation cohort were defined, representing 60% and 40% of the entire database, respectively, and a Cox proportional hazards model was fitted. Atrial fibrillation incidence was 7.24 per 1000 person-years (95% confidence interval, 7.08-7.40). The final model included age, weight, total cholesterol, heart failure, valvular heart disease, and antihypertensive treatment. Its concordance index (standard error) was 0.769 (0.004) and 0.768 (0.005) in the derivation and validation datasets, respectively. This research provides a tool, built with variables from daily clinical practice, that can be readily used in the primary care setting to predict atrial fibrillation incidence in the hypertensive population without ischemic vascular disease. The tool may help tailor individualized diagnostic and preventive care decisions.

Improving interMediAte risk management. MARK study.

BACKGROUND: Cardiovascular risk functions fail to identify more than 50% of patients who develop cardiovascular disease. This is especially evident in the intermediate-risk patients in which clinical management becomes difficult. Our purpose is to analyze if ankle-brachial index (ABI), measures of arterial stiffness, postprandial glucose, glycosylated hemoglobin, self-measured blood pressure and presence of comorbidity are independently associated to incidence of vascular events and whether they can improve the predictive capacity of current risk equations in the intermediate-risk population. METHODS/DESIGN: This project involves 3 groups belonging to REDIAPP (RETICS RD06/0018) from 3 Spanish regions. We will recruit a multicenter cohort of 2688 patients at intermediate risk (coronary risk between 5 and 15% or vascular death risk between 3-5% over 10 years) and no history of atherosclerotic disease, selected at random. We will record socio-demographic data, information on diet, physical activity, comorbidity and intermittent claudication. We will measure ABI, pulse wave velocity and cardio ankle vascular index at rest and after a light intensity exercise. Blood pressure and anthropometric data will be also recorded. We will also quantify lipids, glucose and glycosylated hemoglobin in a fasting blood sample and postprandial capillary glucose. Eighteen months after the recruitment, patients will be followed up to determine the incidence of vascular events (later follow-ups are planned at 5 and 10 years). We will analyze whether the new proposed risk factors contribute to improve the risk functions based on classic risk factors. DISCUSSION: Primary prevention of cardiovascular diseases is a priority in public health policy of developed and developing countries. The fundamental strategy consists in identifying people in a high risk situation in which preventive measures are effective and efficient. Improvement of these predictions in our country will have an immediate, clinical and welfare impact and a short term public health effect. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01428934.