The effect of external stimulation on functional networks in the aging healthy human brain.

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65 years) and older adults (N =310, $\geq $65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space. We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brain states of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findings could have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-brain dynamics.

Association of metabolic syndrome and its components with arterial stiffness in Caucasian subjects of the MARK study: a cross-sectional trial.

BACKGROUND: The cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) can reflect both central and peripheral arterial stiffness. Metabolic syndrome (MetS) and its components may increase arterial stiffness and the risk of cardiovascular diseases. However, the correlation of MetS and its components with arterial stiffness is still not clear. The primary aim of this study is thus the relationship using baPWV and CAVI in Caucasian adults with intermediate cardiovascular risk. The secondary aim is to analyze sex differences. METHODS: This study analyzed 2351 subjects aged 35-74 years (mean, 61.4 ± 7.7 years) comprising 61.7 % males and enrolled in the improving interMediAte Risk management (MARK) study. CAVI was measured using a VaSera VS-1500 ® device, and baPWV was calculated using a validated equation. MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. RESULTS: MetS was found in 51.9 % of the subjects. All MetS components except reduced HDL-cholesterol (p = 0.578) were associated with CAVI. High density lipoprotein cholesterol (p = 0.075) and waist circumference (p = 0.315) were associated with baPWV. The different MetS components that assess dyslipidemia using the stiffness measures show different associations according to patient sex. The high blood pressure component had a greater odds ratio (OR) for both baPWV ≥ 17.5 m/sec (OR = 6.90, 95 % CI 3.52-13.519) and CAVI ≥ 9 (OR = 2.20, 95 % CI 1.63-1.90). CONCLUSIONS: MetS and all its components (except HDL-cholesterol with baPWV and CAVI and WC with baPWV) were associated with baPWV and CAVI. However, there were sex differences in the association of MetS and its components with baPWV and CAVI. Data from this study suggest a greater association of CAVI and baPWV values with MetS components in males than in females and indicate greater arterial stiffness in the event of simultaneously elevated blood pressure, fasting plasma glucose, and waist circumference. Trial Registration Clinical Trials.gov Identifier: https://clinicaltrials.gov/ct2/show/ NCT01428934. Registered 2 September 2011. Last updated September 8, 2016.

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.

Association between markers of glycemia and carotid intima-media thickness: the MARK study.

BACKGROUND: Carotid intima-media thickness (C-IMT) is a reliable predictor of cardiovascular events. We Investigated the relationship between markers of glycemia and C-IMT in intermediate-risk cardiovascular patients. METHODS: This study analyzed 427 subjects, aged 35 to 74 years (mean, 60.3 ± 8.5 years), 55 % women, enrolled into the MARK study. Including 231 subjects defined as normal glucose, 104 subjects classified as prediabetes and 92 with type 2 diabetes mellitus. Carotid ultrasound was used to measure C-IMT and the presence of plaques. Fasting plasma glucose (mg/dl) and glycated hemoglobin (%) (HbA1c) were measured using standard enzymatic automated methods. Postprandial glucose (mg/dl) was self-measured by patients at home 2 h after meals (breakfast, lunch and dinner) for 1 day. RESULTS: The C-IMT shows a positive correlation with fasting plasma glucose, postprandial glucose and HbA1c. Multiple linear regression analysis showed a positive association between HbA1c and C-IMT, with a 0.016 mm and 0.019 mm increase in mean and maximum C-IMT per 1 % increase in HbA1c. In addition, an association between fasting plasma glucose and C-IMT was found with an increase of 0.004 and 0.005 mm in mean and maximum C-IMT per 10 mg/dl in fasting plasma glucose. We also observed a graded association between fasting plasma glucose, postprandial glucose and HbA1c and the presence of carotid target organ damage (TOD), with an odds ratio of 1.013, 1.010 and 1.425, respectively. CONCLUSION: The results of this study suggest that the fasting plasma glucose and HbA1c, but not postprandial glucose, are associated with C-IMT media and maximum. The patients who present with a metabolic glucose alteration have more risk of developing carotid TOD. TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT01428934 .

Vascular structure and function and their relationship with health-related quality of life in the MARK study.

BACKGROUND: There is limited evidence concerning the relationship between vascular disease and health-related quality of life (HRQL). We investigated the relationship between vascular structure and function with health-related quality of life in a population with intermediate cardiovascular risk. METHODS: This study analyzed 303 subjects with ankle-brachial index (ABI) values ranging from 0.9 to 1.4 who were included in the MARK study (age 35 to 74 years; mean:60.5 ± 8.5), of which 50.2 % were women. Measurements included: ABI, brachial-ankle pulse wave velocity (ba-PWV), and cardio-ankle vascular index (CAVI), all measured using the VaSera device. The central augmentation index was adjusted to 75 lpm (AIx_75) using the Mobil-O-Graph device. HRQL was assessed by the Spanish version of the SF-12, version2. The highest obtained CAVI and ba-PWV values and the lowest ABI values were considered for the study. RESULTS: The cohort was composed of21 % smokers, 76 % hypertensive patients, and 24 % diabetic patients. The ABI mean was 1.09 ± 0.07,the ba-PWV mean was 14.64 ± 2.55 m/s with a 12.9 % of subjects higher than 17.5 m/s, AIx_75 26.46 ± 14.05, and CAVI 8.61 ± 1.08 with a 36.6 % of subjects higher than 9. Men scored higher than women in the HRQL measurements for physical (PSC-12; 49.9 vs. 46.9, p = 0.004) and mental (MSC-12) domains (51.2 vs. 47.7, p = 0.003). Age was positively correlated with CAVI (r = 0.547), ba-PWV (r = 0.469), AIx_75 (r = 0.255, p < 0.01), and the MSC-12 (r = 0.147, p < 0.05), but not the PSC-12. In the adjusted multiple linear regression analysis, the positive association of ABI and CAVI with the PSC-12 was maintained. CONCLUSIONS: The ABI in the normal range has a positive association with the PSC-12 of HRQL evaluated with the SF-12. The CAVI also showed a positive association with the PSC-12 of HRQL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01428934 .

Association of physical activity with vascular aging in a population with intermediate cardiovascular risk, analysis by sex: MARK study.

BACKGROUND: The aim of this study was to analyze the association of physical activity and its intensity with arterial stiffness and vascular aging and differences by sex in a Spanish population with intermediate cardiovascular risk. METHODS: Cross-sectional study. A total of 2475 individuals aged 35-75 years participated in the study. Brachial-ankle pulse wave velocity (baPWV) was measured using a VaSera VS-1500® device. Based on the age and sex percentile presented by the participants, the latter were classified as follows: those with a percentile above 90 and presenting established cardiovascular disease were classified as early vascular aging (EVA); those with a percentile between 10 and 90 were classified as normal vascular aging (NVA) and those with a percentile below 10 were classified as healthy vascular aging (HVA). Physical activity was analyzed through the short version of the Minnesota Leisure Time Physical Activity Questionnaire (MLTPAQ). RESULTS: The mean age of the participants was 61.34 ± 7.70 years, with 61.60% men. Of the total sample, 86% were sedentary (83% men vs 90% women). The total physical activity showed a negative association with baPWV (ß = - 0.045; 95% CI - 0.080 to - 0.009). Intense physical activity showed a negative relationship with baPWV (ß = - 0.084; 95% CI - 0.136 to - 0.032). The OR of the total physical activity and the intense physical activity carried out by the subjects classified as NVA with respect to those classified as HVA was OR = 0.946; (95% CI 0.898 to 0.997) and OR = 0.903; (95% CI 0.840 to 0.971), and of those classified as EVA it was OR = 0.916; (95% CI 0.852 to 0.986) and OR = 0.905; (95% CI 0.818 to 1.000). No association was found with moderate- or low-intensity physical activity. CONCLUSIONS: The results of this study suggest that, when intense physical activity is performed, the probability of presenting vascular aging is lower. In the analysis by sex, this association is only observed in men.

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.

Multiple risk behaviour intervention to prevent depression in primary care.

BACKGROUND: Primary care is the ideal setting for promotion and prevention intervention. Multiple risk behaviour interventions present several advantages over single-risk lifestyle interventions. Multiple risk behaviour interventions could be easily implemented in primary care to prevent non-communicable disease and depression. AIM: To test the effectiveness of a multiple risk behaviour intervention to promote Mediterranean diet, physical activity, and/or smoking cessation in people attending Spanish primary health care with incidence of depression and symptoms of depression. METHOD: This was a secondary analysis of the EIRA study that aims to test the effectiveness of a multiple risk behaviour intervention to promote healthy lifestyles. Twenty-six primary care centres were randomised to receive multiple risk behaviour intervention or usual care. The multiple risk behaviour intervention included individual sessions, group sessions, communitarian activities, and SMS reception. Participants were followed for 10-14 months. The primary outcomes of this study were incidence of depression and reductions of depressive symptoms. RESULTS: Three thousand and sixty-seven participants were included. Females accounted for 45.13% and 93.88% were Spanish. Age varied between 45 and 75 years old. The effectiveness of the intervention will be calculated using the Patient Health Questionnaire (PHQ-9) and the Composite International Diagnostic Interview ( CIDI) depression section. Linear and logistic regression will be used to create predictive models. CONCLUSION: Primary care is the most accessible service in the health system for patients. Hence primary care is the ideal setting for health education, promotion, and prevention interventions. This study will provide high-quality evidence about the effectiveness of multiple risk behaviour interventions over depression prevention.

Capacity adiposity indices to identify metabolic syndrome in subjects with intermediate cardiovascular risk (MARK study).

BACKGROUND: Obesity increases mortality, and is linked to cardiovascular diseases and metabolic syndrome (MetS). Therefore, the purpose of this study was to analyze the ability of different adiposity indices to identify subjects with MetS among people with intermediate cariovascular risk. MATERIALS AND METHODS: The cross-sectional study involved 2478 subjects, recruited by the MARK study. Adiposity measures: general adiposity by body mass index (BMI), central adiposity by waist-to-height ratio (WHtR), fat mass percent by the Clínica Universidad de Navarra-body adiposity estimator (CUN-BAE), percentage of body fat and of visceral adipose tissue by body roundness index (BRI) and visceral obesity and general adiposity with body shape index (ABSI). The diagnosis of MetS was made in accordance with the criteria established in the international consensus of the Joint Scientific Statement National Cholesterol Education Program III. RESULTS: The highest correlation coefficients were obtained by the glycemic components (HbA1c and FPG) of the MetS and ranged from 0.155 to 0.320. The exception was ABSI, which showed lower values in the global analysis and in the males. Values of the area under the ROC curve with the adiposity indices ranged from 0.773 with the BMI in males to 0.567 with ABSI in males. In the logistic regression analysis, all adiposity factors, except ABSI, showed similar OR values of MetS after adjusting for possible confounding factors. In the global analysis, the adiposity index that showed a highest OR of MetS was CUN-BAE (OR 5.50; 95% CI 4.27-7.09). In the analysis by gender, the highest ORs were BMI in males (OR 5.98; 95% CI 4.70-7.60) and both WHtR and BRI in females (OR 4.15; 95% CI 3.09-5.58). CONCLUSION: All adiposity indices, except for ABSI, show an association with MetS and similar ability to detect subjects with MetS among people with intermediate cariovascular risk.

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.

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

The purpose was to analyze statin effectiveness in a general population with differing levels of coronary heart disease (CHD) risk. Patients (35-74 years) without previous cardiovascular disease were included and stratified according to 10-year CHD risk (<5%, 5-7.4%, 7.5-9.9%, and 10-19.9%). New users were categorized according to their medical possession ratio (MPR). The main outcome was atherosclerotic cardiovascular disease (ASCVD) (myocardial infarction and ischemic stroke). In adherent patients (MPR 70%), statin treatment decreased ASCVD risk across the range of coronary risk (from 16-30%). The 5-year number needed to treat (NNT) was 470 and 204 in the risk categories <5% and 5-7.4%, respectively, and 75 and 62 in the 7.5-9.9% category than in the 10-19.9% category, respectively. Statin therapy should remain a priority in patients at high 10-year CHD risk (10-19.9%). Most patients with intermediate risk could benefit from statin treatment, but the treatment decision should focus on the net benefit, safety, and patient preference, given the higher NNT.

Acute Myocardial Infarction Population Incidence and Mortality Rates, and 28-day Case-fatality in Older Adults. The REGICOR Study.

INTRODUCTION AND OBJECTIVES: Our aims were to determine acute myocardial infarction (AMI) incidence and mortality rates, and population and in-hospital case-fatality in the population older than 74 years; variability in clinical characteristics and AMI management of hospitalized patients, and changes in the incidence and mortality rates, case-fatality, and management by age groups from 1996 to 1997 and 2007 to 2008. METHODS: A population-based AMI registry in Girona (Catalonia, Spain) including individuals with suspected AMI older than 34 years. RESULTS: The incidence rate increased with age from 169 and 28 cases/100 000 per year in the group aged 35 to 64 years to 2306 and 1384 cases/100 000 per year in the group aged 85 to 94 years, in men and women, respectively. Population case-fatality also increased with age, from 19% in the group aged 35 to 64 years to 84% in the group aged 85 to 94 years. A lower population case-fatality was observed in the second period, mainly explained by a lower in-hospital case-fatality. The use of invasive procedures and effective drugs decreased with age but increased in the second period in all ages up to 84 years. CONCLUSIONS: Acute myocardial infarction incidence, mortality, and case-fatality increased exponentially with age. There is still a gap in the use of invasive procedures and effective drugs between younger and older patients.

A body shape index and vascular structure and function in Spanish adults (MARK study): A cross-sectional study.

A body shape index (ABSI) has been introduced as a marker of the relationship between body composition and all-cause mortality. However, until now, the relationships between ABSI and vascular structure and function have not been evaluated. The aim of this study was to investigate the association of ABSI with vascular structure and function in Spanish adults with intermediate cardiovascular risk. This cross-sectional study analyzed the data of 2354 subjects [age, 35-74 years (median, 62.0 years [range, 56.0-67.0 years]), 61.9% men] enrolled into the MediAte Risk management (MARK) study. ABSI was calculated by using the following formula: ABSI = waist circumference (m)/[body mass index × height (m))]. Vascular function was assessed by measuring cardio-ankle vascular index (CAVI) with the VaSera device and brachial ankle pulse wave velocity (baPWV) by using a validated equation. Vascular structure was assessed by measuring carotid intima-media thickness (IMT) by ultrasonography. Median value of ABSI was 0.083 (range, 0.081-0.090), mean CAVI was (8.5 ±â€Š1.2), and median IMT was 0.727 (range, 0.672-0.799). The values of ABSI and CAVI were higher in men. After adjusting for confounders, ABSI was positively associated with CAVI, baPWV, and average mean IMT. Thus, for each unit increase in ABSI, CAVI increased by 0.16 units, baPWV by 0.25 m/s, and IMT by 0.033 mm. In the logistic regression analysis, the odds ratio of ABSI was > 1 for high CAVI ≥ 9, baPWV ≥ 15 m/s, and IMT ≥ 0.90 mm in the overall subject group, and in the sex- and age-specific (> 62 years, ≤ 62 years) subgroups, after adjusting for confounders. The area under the receiver-operating characteristic curve of the ABSI was 0.631 (95% confidence interval [CI], 0.608-0.654) for CAVI ≥ 9, and 0.617 (95% CI, 0.593-0.641) for high baPWV ≥ 15 m/s. ABSI showed a positive association with vascular structure and function, independent of other confounders that might influence weight and fat mass distribution in Spanish subjects at intermediate cardiovascular risk.Trial Registration: ClinicalTrials.gov Identifier: NCT01428934 (registered: September 2, 2011; last updated: September 8, 2016).

The association between education and cardiovascular disease incidence is mediated by hypertension, diabetes, and body mass index.

Education and cardiovascular disease (CVD) are inversely associated but the mediating factors have not been totally elucidated. Our aim was to analyze the mediating role of modifiable risk factors. Cohort study using the REGICOR population cohorts. Participants without previous CVD were included (n = 9226). Marginal structural models were used to analyze the association between education and CVD incidence at 6 years of follow-up. Mediation by modifiable risk factors (diabetes, dyslipidemia, hypertension, smoking, body mass index, and physical activity) was assessed using the counterfactual framework. Participants with a university degree had a CVD incidence hazard ratio (HR) of 0.51 (95% confidence interval (CI) = 0.30, 0.85), compared to those with primary or lower education. Only hypertension, BMI, and diabetes mediated the association between education and CVD incidence, accounting for 26% of the association (13.9, 6.9, and 5.2%, respectively). Sensitivity analyses showed that hypertension was the strongest mediator (average causal mediation effect [95% CI] = increase of 2170 days free of CVD events [711, 4520]). The association between education and CVD incidence is partially mediated by hypertension, BMI, and diabetes. Interventions to decrease the prevalence of these risk factors could contribute to diminish the CVD inequalities associated with educational level.

Glycemic markers and relation with arterial stiffness in Caucasian subjects of the MARK study.

BACKGROUND: Effect of prediabetes and normal glucose on arterial stiffness remains controversial. The primary aim of this study was to investigate the relationship of fasting plasma glucose (FPG), postprandial glucose (PG) and glycosylated haemoglobin (HbA1c) with brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) in Caucasian adults. The secondary aim was to analyse this relationship by glycaemic status. METHODS: Cross-sectional study. Setting: Primary care. Participants: 2,233 subjects, 35-74 years. Measures: FPG (mg/dL) and HbA1c (%) of all subjects were measured using standard automated enzymatic methods. PG (mg/dL) was self-measured at home two hours after meals (breakfast, lunch and dinner) for one day using an Accu-chek ® glucometer. CAVI was measured using a VaSera VS-1500® device (Fukuda Denshi), and baPWV was calculated using a validated equation. RESULTS: CAVI and baPWV values were significantly higher in subjects with diabetes mellitus than in glucose normal and prediabetes groups (p<0.001). FPG, PG and HbA1c were positively associated with CAVI and baPWV. The ß regression coefficient for: HbA1c was 0.112 (CI 95% 0.068 to 0.155) with CAVI, 0.266 (CI 95% 0.172 to 0.359) with baPWV; for PG was 0.006 (CI 95% 0.004 to 0.009 and for FPG was 0.005 (CI 95% 0.002 to 0.008) with baPWV; and for PG was 0.002 (CI 95% 0.001 to 0.003) and 0.003 (CI 95% 0.002 to 0.004) with CAVI (p<0.01 in all cases). When analysing by hyperglycaemic status, FPG, PG and HbA1c were positively associated with CAVI and baPWV in subjects with type 2 diabetes mellitus. CONCLUSION: FPG, PG and HbA1c show a positive association with CAVI and baPWV, in Caucasian adults with intermediate cardiovascular risk factors. When analysing by hyperglycaemic status, the association is only maintained in subjects with type 2 diabetes mellitus. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT01428934. Registered 2 September 2011. Retrospectively registered. Last updated September 8, 2016.

Adiposity measures and arterial stiffness in primary care: the MARK prospective observational study.

BACKGROUND: The cardiovascular risk of obesity is potentially increased by arterial stiffness. OBJECTIVE: To assess the relationship of adiposity measures with arterial stiffness in Caucasian adults with intermediate cardiovascular risk. SETTING: Six Spanish health centres. PARTICIPANTS: We enrolled 2354 adults (age range, 35-74 years; mean age, 61.4±7.7 years, 61.9% male). METHODS: This is a cross-sectional study that analyses data from the baseline visit of the improving interMediAte RisK management (MARK) study. The main outcome variables were body mass index (BMI), waist-to-height ratio (WHtR), Clínica Universidad de Navarra-body adiposity estimation (CUN-BAE) body fat percentage and body roundness index (BRI). Vascular function was assessed by the cardio-ankle vascular index (CAVI) with the VaSera device; brachial-ankle pulse wave velocity (baPWV) was determined using a validated equation. RESULTS: The mean adiposity measures were a BMI of 29.2±4.4, WHtR of 0.61±0.07, CUN-BAE of 35.7±1.7 and BRI of 5.8±1.7. The mean stiffness measures were a CAVI of 8.8±1.2 and baPWV of 14.9±2.5. In multiple linear regression analyses, all adiposity measures were negatively associated with CAVI and baPWV (p<0.01 for all) after adjustment for possible factors of confusion. The proportion of CAVI variability via the adiposity measures were 5.5% for BMI, 5.8% for CUN-BAE, 3.8% for WHtR and 3.7% for BRI. These were higher among diabetic, obese, younger (≤62 years) and non-hypertensive subjects who had similar activity and sedentary profiles. CONCLUSIONS: Adiposity measures are negatively associated with arterial stiffness measures. The percentage of variation in CAVI explained by its relation to the different measures of adiposity ranges from 5.8% (CUN-BAE) to 3.7% (BRI). In the case of baPWV, it oscillates between 0.7% (CUN-BAE and BMI) and 0.1% (WHtR). TRIAL REGISTRATION NUMBER: NCT01428934.

Patterns of statin use and cholesterol goal attainment in a high-risk cardiovascular population: A retrospective study of primary care electronic medical records.

OBJECTIVE: To describe real-life patterns of statin use and cholesterol goal attainment in a retrospective cohort of patients with high cardiovascular risk. METHODS: Retrospective cohort study of 21,636 individuals, 18.34% women, mean age 63.30 years (standard deviation 6.29). New statin users aged 35 to 74 years at high cardiovascular risk and with no previous cardiovascular disease in primary care electronic medical records (2006-2011). Patterns of statin use were based on statin type, potency, and 1-year statin switches. OUTCOMES: Relative mean reductions over 1 year and probability of goal attainment (<3.3 mmol/L). Natural patterns of statin use were identified using multiple correspondence analysis; general linear and logistic models were used to estimate low-density lipoprotein cholesterol (LDL-C) reductions and goal attainment probability. RESULTS: Three patterns of statin use were defined: low (3.82% of the population), moderate (71.94%), and high intensity (24.24%). After 1 year, potency decreased 42.74%, 64.16%, and 50.94%, respectively, and 37.41%, 29.47%, and 30.16% of the population stopped taking statins in low, moderate, and high patterns, respectively. Relative reductions in LDL-C: low intensity, 15.7% (95% confidence interval [CI]: -22.96 to 54.36); moderate intensity, 29.72% (95% CI: 29.12-30.32); and high intensity, 24.20% (95% CI: -8.08 to 40.32). There was a direct relationship between higher intensity patterns and greater probability of goal attainment. CONCLUSIONS: Three real-life patterns of statin use were identified. Lipid management strategies in primary care should focus on improving adherence to treatment. People starting at low potency should switch to a moderate pattern; more intensive therapies should be considered in who require a larger LDL-C reduction to reach therapeutic targets, patients with good treatment adherence who do not achieve the goal with a moderate pattern of therapy or patients at very high risk.

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.