Dysregulation of Lipid Metabolism Serves as A Link Between Alzheimer's and Cardiovascular Disease, As Witnessed in A Cross-Sectional Study.

Cardiovascular risk factors and established cardiovascular disease (CVD) increase the risk of suffering dementia of the Alzheimer's type (DAT). Here, we set out to define specific molecular profiles of CVD in patients with DAT to better understand its relationship, to unravel the mechanisms underlying the high risk of developing DAT in CVD patients and to define new markers of early disease. Plasma samples from patients with DAT, with and without CVD, were analyzed through a multiomics approach, with integration of metabolomics and proteomics datasets using the OmicsNet web-based tool. Metabolomics results showed an enrichment in lipids and lipid-like molecules. Similarly, the most significant cluster identified through proteomics was formed by 5 proteins related to lipoprotein and cholesterol metabolism. After integration and functional enrichment, glycerolipid metabolism, fatty acid degradation and sphingolipid metabolism were among the most significant functions. Finally, differential expression of ABCA1 and APOH proteins was verified, in an independent cohort also including controls and patients with CVD alone. Both proteins positively correlated with phospho-Tau (181), a classical hallmark of DAT. Different molecular profiles exist in patients with DAT, with and without CVD, with exacerbated alterations in patients in which DAT and CVD co-exist. This information may help to define biomarkers like ABCA1 and APOH that identify patients with cardiovascular dysfunction that are at high risk of developing DAT. Such markers will allow more personalized interventions to be selected, a further step towards precision medicine for individuals whose molecular profiles indicate a distinct response to the same management strategies.

Analysis of Global Oxidative Status Using Multimarker Scores Reveals a Specific Association Between Renal Dysfunction and Diuretic Therapy in Older Adults.

Aging and chronic kidney disease (CKD) are important interrelated cardiovascular risk (CVR) factors linked to oxidative stress, but this relationship has not been well studied in older adults. We assessed the global oxidative status in an older population with normal to severely impaired renal function. We determined the oxidative status of 93 older adults (mean age 85 years) using multimarker scores. OxyScore was computed as index of systemic oxidative damage by analyzing carbonyl groups, oxidized low-density lipoprotein, 8-hydroxy-2'-deoxyguanosine, and xanthine oxidase activity. AntioxyScore was computed as index of antioxidant defense by analyzing catalase and superoxide dismutase (SOD) activity and total antioxidant capacity. OxyScore and AntioxyScore were higher in subjects with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 than in peers with eGFR >60 mL/min/1.73 m2, with protein carbonyls, catalase, and SOD activity as major drivers. Older adults with a recent cardiovascular event had similar OxyScore and AntioxyScore as peers with eGFR >60 mL/min/1.73 m2. Multivariate linear regression analysis revealed that both indices were associated with decreased eGFR independently of traditional CVR factors. Interestingly, AntioxyScore was also associated with diuretic treatment, and a more pronounced increase was seen in subjects receiving combination therapy. The associations of AntioxyScore with diuretic treatment and eGFR were mutually independent. In conclusion, eGFR is the major contributor to the imbalance in oxidative stress in this older population. Given the association between oxidative stress, CKD, and CVR, the inclusion of renal function parameters in CVR estimators for older populations, such as the SCORE-OP, might improve their modest performance.

Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations.

The predictive value of traditional cardiovascular risk estimators is limited, and young and elderly populations are particularly underrepresented. We aimed to investigate the urine metabolome and its association with cardiovascular risk to identify novel markers that might complement current estimators based on age. Urine samples were collected from 234 subjects categorized into three age-grouped cohorts: 30-50 years (cohort I, young), 50-70 years (cohort II, middle-aged), and > 70 years (cohort III, elderly). Each cohort was further classified into three groups: (a) control, (b) individuals with cardiovascular risk factors, and (c) those who had a previous cardiovascular event. Novel urinary metabolites linked to cardiovascular risk were identified by nuclear magnetic resonance in cohort I and then evaluated by target mass spectrometry quantification in all cohorts. A previously identified metabolic fingerprint associated with atherosclerosis was also analyzed and its potential risk estimation investigated in the three aged cohorts. Three different metabolic signatures were identified according to age: 2-hydroxybutyrate, gamma-aminobutyric acid, hypoxanthine, guanidoacetate, oxaloacetate, and serine in young adults; citrate, cyclohexanol, glutamine, lysine, pantothenate, pipecolate, threonine, and tyramine shared by middle-aged and elderly adults; and trimethylamine N-oxide and glucuronate associated with cardiovascular risk in all three cohorts. The urinary metabolome contains a metabolic signature of cardiovascular risk that differs across age groups. These signatures might serve to complement existing algorithms and improve the accuracy of cardiovascular risk prediction for personalized prevention. KEY MESSAGES: • Cardiovascular risk in the young and elderly is underestimated. • The urinary metabolome reflects cardiovascular risk across all age groups. • Six metabolites constitute a metabolic signature of cardiovascular risk in young adults. • Middle-aged and elderly adults share a cardiovascular risk metabolic signature. • TMAO and glucuronate levels reflect cardiovascular risk across all age groups.

Novel molecular plasma signatures on cardiovascular disease can stratify patients throughout life.

Several models are available to calculate the risk of developing cardiovascular complications in mid-life. The estimation of lifetime risk in the long-term remains an unmet clinical need. We previously identified new molecular plasma signatures for cardiovascular risk stratification in a young population (30-50-years old). The aim of the present study was to determine if the specific signature found in young population changes with age. Proteomic analysis was performed in plasma samples obtained from different age groups, middle-age (50-70-years old, n = 63) and elderly (>70-years old, n = 61), which, in turn were classified into 3 subgroups according to cardiovascular risk. Our previous results in a young population clearly showed two different proteomic signatures. Building on these findings, targeted-mass spectrometry and turbidimetry analyses were used to test these signatures in middle-age and elderly populations. This strategy identified three common proteomic signatures between young and adult patients related to cardiovascular stratification, organ damage and risk prediction. Furthermore, receiver operating characteristic analysis revealed the potential value of these novel markers for lifetime risk stratification. Our results provide new insight into altered molecular mechanisms in the pathogenesis of cardiovascular disease and, more importantly, identify novel protein panels that can stratify patients throughout life. SIGNIFICANCE: Our results revealed three common proteomic signatures between young and adult patients related to cardiovascular stratification, organ damage and risk prediction. The results obtained provide a deeper insight into the pathogenesis of CV diseases and allow the identification of novel protein panels to stratify patients according to CV risk throughout life. While current estimators calculate the risk of having a CV event considering age as the most important factor to CV disease, our results represent an alternative to traditional CV risk factors, allowing the stratification of CV risk regardless of the age. Using a combination of traditional markers and established algorithms with these findings as a future preventive strategy, could facilitate an adequate assessment of CV risk.

Diferencias entre el control clínico y ambulatorio de la hipertensión arterial en pacientes muy ancianos. Proyecto CARDIORISC–MAPAPRES / Differences between office and ambulatory control of hypertension in very elderly patients. The CARDIORISC – MAPAPRES project

Fundamento y objetivos: La hipertensión arterial (HTA) afecta a la mayoría de la población muy anciana. El objetivo de este estudio fue estimar el grado de control de la HTA según se registre la presión arterial (PA) en la consulta o por monitorización ambulatoria de PA (MAPA). Pacientes y método: Estudio transversal y multicéntrico sobre pacientes hipertensos de 80 o más años de edad con tratamiento farmacológico antihipertensivo incluidos en el proyecto CARDIORISC–MAPAPRES. Entre junio de 2004 y abril de 2007 se obtuvo una base de datos de 33.829 registros de MAPA que cumplieron estándares de calidad preestablecidos. Se definió como buen control clínico a valores de PA menores de 140/90mmHg, y como buen control ambulatorio a valores de PA por MAPA en período de 24h menores de 130/80mmHg.Resultados: Se identificaron 2.311 pacientes (6,8%) de 80 o más años de edad. La edad media fue de 83,1 años (DE de 3,2) y un 63% fueron mujeres. El 21,5% (intervalo de confianza [IC] del 95%: 19,1–23,9) presentó buen control clínico y un 42,1% (IC del 95%: 39,7–45,3) presentó buen control ambulatorio (p<0,001). La prevalencia de HTA enmascarada fue del 7,0% (IC del 95%: 6,0–8,0) y la prevalencia de resistencia aislada en la clínica fue del 27,6% (IC del 95%: 25,7–29,4). La diabetes, la enfermedad renal crónica y la duración de la HTA fueron los factores más asociados al mal control de la HTA (p<0,001) en la MAPA de 24h.Conclusiones: Sólo 2 de cada 10 pacientes muy ancianos hipertensos tuvieron controlada adecuadamente su HTA por medida casual. Sin embargo, prácticamente el doble estaban controlados con el criterio de la MAPA. Estos hallazgos justifican un uso más amplio de la MAPA en el paciente hipertenso de edad muy avanzada (AU)

Background and objective: Hypertension is highly prevalent in the very elderly. We studied control rates of hypertension according to clinic blood pressure (BP) and ambulatory BP monitoring (ABPM) in treated hypertensives aged ≥80 years.Patients and method: Data came from the Spanish Society of Hypertension ABPM Registry (CARDIORISC – MAPAPRES project), which comprises a nation-wide network of more than 1,000 physicians sending standardized ABPM registries via web. Between June 2004 and April 2007 we obtained a 33.829-patient database. Control of hypertension was defined at the clinic when office BP was <140/90mmHg and at the ABPM when mean BP during the 24-h period was <130/80mmHg.Results: We identified 2,311 patients (6.8%) aged ≥80 years. Mean age (SD) was 83.1 (3.2) years and 63% were women. Control of clinic BP was observed in 21.5% of cases (95%CI: 19.1–23.9) and control of 24-h BP in ABPM was 42.1% (95%CI: 39.7–45.3). Prevalence of masked hypertension was 7.0% (95%CI: 6.0–8.0) and prevalence of office-resistant control (white coat) was 27.6% (95% CI: 25.7–29.4). Diabetes, kidney disease, and duration of hypertension were associated with lack of control in ABPM. Conclusions: In very old hypertensives, control of clinic BP was 21.5% but ambulatory-based hypertension control was 42.1%. Physicians should be aware that the likelihood of misestimating BP control is high in these subjects. A wider use of ABPM in the elderly with hypertension should be considered (AU)

[Differences between office and ambulatory control of hypertension in very elderly patients. The CARDIORISC - MAPAPRES project]. / Diferencias entre el control clínico y ambulatorio de la hipertensión arterial en pacientes muy ancianos. Proyecto CARDIORISC-MAPAPRES.

BACKGROUND AND OBJECTIVE: Hypertension is highly prevalent in the very elderly. We studied control rates of hypertension according to clinic blood pressure (BP) and ambulatory BP monitoring (ABPM) in treated hypertensives aged > or =80 years. PATIENTS AND METHOD: Data came from the Spanish Society of Hypertension ABPM Registry (CARDIORISC - MAPAPRES project), which comprises a nation-wide network of more than 1,000 physicians sending standardized ABPM registries via web. Between June 2004 and April 2007 we obtained a 33.829-patient database. Control of hypertension was defined at the clinic when office BP was <140/90mmHg and at the ABPM when mean BP during the 24-h period was <130/80mmHg. RESULTS: We identified 2,311 patients (6.8%) aged > or =80 years. Mean age (SD) was 83.1 (3.2) years and 63% were women. Control of clinic BP was observed in 21.5% of cases (95%CI: 19.1-23.9) and control of 24-h BP in ABPM was 42.1% (95%CI: 39.7-45.3). Prevalence of masked hypertension was 7.0% (95%CI: 6.0-8.0) and prevalence of office-resistant control (white coat) was 27.6% (95% CI: 25.7-29.4). Diabetes, kidney disease, and duration of hypertension were associated with lack of control in ABPM. CONCLUSIONS: In very old hypertensives, control of clinic BP was 21.5% but ambulatory-based hypertension control was 42.1%. Physicians should be aware that the likelihood of misestimating BP control is high in these subjects. A wider use of ABPM in the elderly with hypertension should be considered.

Optimización del tratamiento médico en pacientes geriátricos con fractura de cadera. Influencia del equipo consultor geriátrico / Optimization of medical treatment in elderly patients with hip fracture. Influence of a geriatric assessment team

Introducción: evaluar la influencia de un equipo consultor geriátrico (ECG) en la prescripción de fármacos a ancianos con fractura de cadera en fase aguda. Material y métodos: estudio prospectivo, controlado, que compara dos grupos: los pacientes tratados por el ECG y los no tratados por este equipo. Se determinan las diferencias en ingesta de fármacos antes y después del proceso. Todas las diferencias se han considerado estadísticamente significativas cuando p < 0,05. Resultados: se estudió a 449 pacientes, edad media de 83,0 años (83% mujeres). Los pacientes tratados por el ECG tomaban más medicamentos antes del ingreso, durante éste y en el momento del alta (todas las diferencias con p < 0,001). También a estos pacientes se les realizó mayor número de diagnósticos que a los del grupo control. Los pacientes consultados al ECG recibieron más transfusiones (p < 0,01), se les prescribió con más frecuencia calcio y vitamina D, neurolépticos, paracetamol, suplementos proteicos y laxantes que el resto (p < 0,001). Los no consultados al ECG obtuvieron peor resultado funcional en el alta. Conclusiones: los pacientes seguidos en la unidad de geriatría tomaron más fármacos antes del ingreso y durante éste, pero también se detectaron más diagnósticos. La prescripción del ECG tiende a optimizar el tratamiento ya que la administración de fármacos se dirige a problemas frecuentes en estos pacientes (anemia, desnutrición, osteoporosis, estreñimiento), que en el grupo control son insuficientemente detectados y tratados. Estas diferencias podrían explicar, en parte, la mejor evolución que presentan los pacientes con fractura de fémur seguidos por los ECG

Introduction: to evaluate the influence of a geriatric assessment team (GAT) on the prescription of drugs in elderly patients with hip fracture in the acute phase. Material and methods: we performed a prospective, controlled trial comparing two groups: patients managed by the GAT and patients that were not. Differences between drug intake before admission and at discharge were calculated (the level of significance was set to p < 0.05). Results: a total of 449 patients were studied. The mean age was 83.0 years and 83% were women. GAT patients took more drugs before admission, during hospitalization and at discharge than non-referred patients (all differences with p < 0.001). These patients were found to have a greater number of medical disorders than those in the control group. GAT patients received more transfusions (p < 0.001) and were more frequently prescribed calcium, vitamin D, neuroleptic drugs, paracetamol, nutritional supplements, and laxatives than the control group (p < 0.001). Functional recovery at discharge was less favorable in the control group. Conclusions: GAT patients took a greater number of drugs before admission and during hospitalization and had more diagnoses than the control group. GAT prescription tended to optimize treatment since drug administration is aimed at frequent problems in these patients (anaemia, malnutrition, osteoporosis, pain), which were under-detected and under-treated in the control group. These differences could partly explain the more favorable outcome in patients with hip fracture managed by the GAT