Pharmacological treatment of increased vascular risk and cognitive performance in middle-aged and old persons: six-year observational longitudinal study.

BACKGROUND: Lowering vascular risk is associated with a decrease in the prevalence of cardiovascular disease and dementia. However, it is still unknown whether lowering of vascular risk with pharmacological treatment preserves cognitive performance in general. Therefore, we compared the change in cognitive performance in persons with and without treatment of vascular risk factors. METHODS: In this longitudinal observational study, 256 persons (mean age, 58 years) were treated for increased vascular risk during a mean follow-up period of 5.5 years (treatment group), whereas 1678 persons (mean age, 50 years) did not receive treatment (control group). Cognitive performance was three times measured during follow-up using the Ruff Figural Fluency Test (RFFT) and Visual Association Test (VAT), and calculated as the average of standardized RFFT and VAT score per participant. Because treatment allocation was nonrandomized, additional analyses were performed in demographic and vascular risk-matched samples and adjusted for propensity scores. RESULTS: In the treatment group, mean (SD) cognitive performance changed from - 0.30 (0.80) to - 0.23 (0.80) to 0.02 (0.87), and in control group, from 0.08 (0.77) to 0.24 (0.79) to 0.49 (0.74) at the first, second and third measurement, respectively (ptrend < 0.001). After adjustment for demographics and vascular risk, the change in cognitive performance during follow-up was not statistically significantly different between the treatment and control group: mean estimated difference, - 0.10 (95%CI - 0.21 to 0.01; p = 0.08). Similar results were found in matched samples and after adjustment for propensity score. CONCLUSION: Change in cognitive performance during follow-up was similar in treated and untreated persons. This suggests that lowering vascular risk preserves cognitive performance.

Clinical Practice Guideline on management of older patients with chronic kidney disease stage 3b or higher (eGFR<45 mL/min/1.73 m2): a summary document from the European Renal Best Practice Group.

The population of patients with moderate and severe CKD is growing. Frail and older patients comprise an increasing proportion. Many studies still exclude this group, so the evidence base is limited. In 2013 the advisory board of ERBP initiated, in collaboration with European Union of Geriatric Medicine Societies (EUGMS), the development of a guideline on the management of older patients with CKD stage 3b or higher (eGFR >45 mL/min/1.73 m2). The full guideline has recently been published and is freely available online and on the website of ERBP (www.european-renal-best-practice.org). This paper summarises main recommendations of the guideline and their underlying rationales.

Geriatric Assessment in CKD Care: An Implementation Study.

Rationale & Objective: Older people with progressive chronic kidney disease (CKD) have complex health care needs. Geriatric evaluation preceding decision making for kidney replacement is recommended in guidelines, but implementation is lacking in routine care. We aimed to evaluate implementation of geriatric assessment in CKD care. Study Design: Mixed methods implementation study. Setting & Participants: Dutch nephrology centers were approached for implementation of geriatric assessment in patients aged ≥70 years and with an estimated glomerular filtration rate of ≤20 mL/min/1.73 m2. Quality Improvement Activities/Exposure: We implemented a consensus-based nephrology-tailored geriatric assessment: a patient questionnaire and professionally administered test set comprising 16 instruments covering functional, cognitive, psychosocial, and somatic domains and patient-reported outcome measures. Outcomes: We aimed for implementation in 10 centers and 200 patients. Implementation was evaluated by (i) perceived enablers and barriers of implementation, including integration in work routines (Normalization Measure Development Tool) and (ii) relevance of the instruments to routine care for the target population. Analytical Approach: Variations in implementation practices were described based on field notes. The postimplementation survey among health care professionals was analyzed descriptively, using an explanatory qualitative approach for open-ended questions. Results: Geriatric assessment was implemented in 10 centers among 191 patients. Survey respondents (n = 71, 88% response rate) identified determinants that facilitated implementation, ie, multidisciplinary collaboration (with geriatricians) -meetings and reports and execution of assessments by nurses. Barriers to implementation were patient illiteracy or language barrier, time constraints, and patient burden. Professionals considered geriatric assessment sufficiently integrated into work routines (mean, 6.7/10 ± 2.0 [SD]) but also subject to improvement. Likewise, the relevance of geriatric assessment for routine care was scored as 7.8/10 ± 1.2. The Clinical Frailty Score and Montreal Cognitive Assessment were perceived as the most relevant instruments. Limitations: Selection bias of interventions' early adopters may limit generalizability. Conclusions: Geriatric assessment could successfully be integrated in CKD care and was perceived relevant to health care professionals.

The number of older persons with kidney failure is increasing, many of whom have cognitive decline or are dependent on others for daily life tasks. These problems are often overlooked but relevant for future treatment choices, and they affect quality of life. We asked 10 health care centers to use tests and questionnaires to identify these issues, thus being able to offer additional support. We learned that it is possible to use these assessments in practice and that professionals found them relevant. Collaboration with geriatric departments was perceived valuable. However, there are also challenges, such as not having enough time and personnel and burden to patients. Understanding these possibilities and challenges is crucial for improving care for older patients with kidney failure.

Cardiovascular risk profile and cognitive function in young, middle-aged, and elderly subjects.

BACKGROUND AND PURPOSE: Cognitive decline occurs earlier than previously realized and is already evident at the age of 45. Because cardiovascular risk factors are established risk factors for cognitive decline in old age, we investigated whether cardiovascular risk factors are also associated with cognitive decline in young and middle-aged groups. METHODS: The cross-sectional study included 3778 participants aged 35 to 82 years (mean age, 54 years) and free of cardiovascular disease and stroke. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; worst score, 0; best score, 12 points). Overall cardiovascular risk was assessed with the Framingham Risk Score (FRS) for general cardiovascular disease (best score, -5; worst score, 33 points). RESULTS: Mean RFFT score (SD) was 70 (26) points, median VAT score (interquartile range) was 10 (9-11) points, and mean FRS (SD) was 10 (6) points. Using linear regression analysis adjusting for educational level, RFFT was negatively associated with FRS. RFFT score decreased by 1.54 points (95% confidence interval, -1.66 to -1.44; P<0.001) per point increase in FRS. This negative association was not only limited to older age groups, but also found in the young (35-44 years). The main influencing components of the FRS were age (P<0.001), diabetes mellitus (P=0.001), and smoking (P<0.001). Similar results were found for VAT score as outcome measure. CONCLUSIONS: In this large population-based cohort, a worse overall cardiovascular risk profile was associated with poorer cognitive function. This association was already present in young adults aged 35 to 44 years.

A review of supportive care for older people with advanced chronic kidney disease.

Supportive care (SC) is a multidimensional and person-centred approach to managing advanced CKD that engages the person and their caregivers in shared decision making from the outset. Rather than focusing on disease-specific therapies, SC is a collection of adjuvant interventions and adaptations to conventional treatments that can be used to improve the individual's quality of life. Recognizing that frailty, multi-morbidity and polypharmacy are more common among older people with advanced chronic kidney disease (CKD) and that people in this group tend to prioritize quality of life over survival as a goal of care, SC represents an important adjunct to disease-specific therapies in CKD management. This review provides an overview of SC in the older person with advanced CKD.

Bedside palliative care and geriatric consultations: adherence rate in hospitalised patients.

OBJECTIVES: This study examined the adherence rate of recommendations of a palliative consultation team (PCT) and a geriatric consultation team (GCT). Secondary aims were to investigate which factors and/or recommendation characteristics influence adherence rates. METHODS: This retrospective cohort study was performed in the Maastricht University Medical Center+ in the Netherlands and included hospitalised patients who received a consultation by the PCT or the GCT. Baseline data on consultations were collected for the total population and for the GCT and PCT separately. The adherence rate of the recommendations was evaluated by checking evidence of implementation. The nature of recommendations given (solicited or unsolicited) was documented per domain (somatic, psychological/cognitive, social, spiritual, functional, and existential). The association with adherence was evaluated for solicited and unsolicited recommendations separately. Exploration of potentially associated factors was performed using OpenEpi. RESULTS: Overall, 507 consultations of individual patients were performed (n=131) by the GCT and (n=376) by the PCT. Most recommendations given were solicited (865/1201=72%). Over 80% of both solicited and unsolicited recommendations were implemented in the majority of domains. No potentially modifiable factors associated with the adherence of the advices were found. CONCLUSIONS: The overall adherence rate of the GCT and PCT consultations was high. In addition, in certain domains, many recommendations were unsolicited. However, also the majority of these recommendations were implemented.

Chronic kidney disease and mortality risk among older patients with type 2 diabetes mellitus (ZODIAC-24).

OBJECTIVE: to investigate the association between a decreased estimated glomerular filtration rate (eGFR), albuminuria and mortality in elderly patients with type 2 diabetes mellitus (T2DM). DESIGN: prospective observational cohort study. SETTING: primary care. SUBJECTS: eight hundred and ten patients, ≥65 years with T2DM. Analyses were performed in age strata: 65-75 (n = 471), >75 (n = 339) years. METHODS: Cox proportional hazard modelling was used to investigate the association between eGFR, albuminuria and all-cause and cardiovascular mortality after a median follow-up of 9.8 years. RESULTS: an eGFR <45 and 45-60 ml/min/1.73 m(2) is associated with increased cardiovascular mortality in patients of 65-75 years, hazard ratio (HR): 3.29 (1.58-6.86) and 1.78 (1.09-2.90), respectively; in those >75 years increased cardiovascular mortality was observed when eGFR was <45 ml/min/1.73 m(2): 2.42 (1.47-3.69). Compared with patients of 65-75 years, an eGFR >60 ml/min/1.73 m(2) and normo-albuminuria, fully adjusted HRs for cardiovascular mortality were 2.26 (1.04-4.92) and 4.86 (2.33-10.15) for those aged 65-75 years, an eGFR of 45-60 ml/min/1.73 m(2) and normo-albuminuria or albuminuria, respectively; HRs were 1.33 (0.67-2.66) and 2.01 (1.02-3.94), respectively, for those >75 years. CONCLUSIONS: an eGFR of 45-60 ml/min/1.73 m(2) in T2DM patients is associated with increased mortality in patients aged 65-75 years but not in those >75 years. Albuminuria is associated with increased mortality in patients >65 years.

Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts.

Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.

Design of a consensus-based geriatric assessment tailored for older chronic kidney disease patients: results of a pragmatic approach.

PURPOSE: Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced chronic kidney disease (CKD). Despite guideline recommendation of geriatric evaluation, routine geriatric assessment is not common in these patients. While high burden of vascular disease and existing pre-dialysis care pathways mandate a tailored geriatric assessment, no consensus exists on which instruments are most suitable in this population to identify geriatric impairments. Therefore, the aim of this study was to propose a geriatric assessment, based on multidisciplinary consensus, to routinely identify major geriatric impairments in older people with advanced CKD. METHODS: A pragmatic approach was chosen, which included focus groups, literature review, inventory of current practices, an expert consensus meeting, and pilot testing. In preparation of the consensus meeting, we composed a project team and an expert panel (n = 33), drafted selection criteria for the selection of instruments, and assessed potential instruments for the geriatric assessment. RESULTS: Selection criteria related to general geriatric domains, clinical relevance, feasibility, and duration of the assessment. The consensus-assessment contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains. Administration of (seven) patient questionnaires and (ten) professional-administered instruments, by nurse (practitioners), takes estimated 20 and 40 min, respectively. Results are discussed in a multidisciplinary meeting including at least nephrology and geriatric expertise, informing nephrology treatment decisions, and follow-up interventions among which comprehensive geriatric assessment. CONCLUSION: This first multidisciplinary consensus on nephrology-tailored geriatric assessment intent to benefit clinical care and enhance research comparability for older patients with advanced CKD.

Mortality and the Use of Antithrombotic Therapies Among Nursing Home Residents with COVID-19.

BACKGROUND/OBJECTIVES: Nursing home (NH) residents are a vulnerable population, susceptible to respiratory disease outbreaks such as coronavirus disease 2019 (COVID-19). Poor outcome in COVID-19 is at least partly attributed to hypercoagulability, resulting in a high incidence of thromboembolic complications. It is unknown whether commonly used antithrombotic therapies may protect the vulnerable NH population with COVID-19 against mortality. This study aimed to investigate whether the use of oral antithrombotic therapy (OAT) was associated with a lower mortality in NH residents with COVID-19. DESIGN: A retrospective case series. SETTING: Fourteen NH facilities from the NH organization Envida, Maastricht, the Netherlands PARTICIPANTS: A total of 101 NH residents with COVID-19 were enrolled. MEASUREMENTS: The primary outcome was all-cause mortality. The association between age, sex, comorbidity, OAT, and mortality was assessed using logistic regression analysis. RESULTS: Overall mortality was 47.5% in NH residents from 14 NH facilities. Age, comorbidity, and medication use were comparable among NH residents who survived and who died. OAT was associated with a lower mortality in NH residents with COVID-19 in the univariable analysis (odds ratio (OR) = 0.89; 95% confidence interval (CI) = 0.41-1.95). However, additional adjustments for sex, age, and comorbidity attenuated this difference. Mortality in males was higher compared with female residents (OR = 3.96; 95% CI = 1.62-9.65). Male residents who died were younger compared with female residents (82.2 (standard deviation (SD) = 6.3) vs 89.1 (SD = 6.8) years; P < .001). CONCLUSION: NH residents in the 14 facilities we studied were severely affected by the COVID-19 pandemic, with a mortality of 47.5%. Male NH residents with COVID-19 had worse outcomes than females. We did not find evidence for any protection against mortality by OAT, necessitating further research into strategies to mitigate poor outcome of COVID-19 in vulnerable NH populations. J Am Geriatr Soc 68:1647-1652, 2020.

The prevalence and impact of falls in elderly dialysis patients: Frail elderly Patient Outcomes on Dialysis (FEPOD) study.

BACKGROUND: As the numbers of older patients on dialysis rise, geriatric problems such as falling become more prevalent. We aimed to assess the prevalence of falls and the impact on mortality and quality of life in frail elderly patients on assisted PD (aPD) and hemodialysis (HD) from the FEPOD Study. METHODS: Data on falls and quality of life were collected with questionnaires at baseline and every six months during 2-year follow-up. Multiple regression analysis was used to evaluate factors associated with falls. Additionally, we performed a review of literature concerning the relation between falls and poor outcome. RESULTS: Baseline fall data were available for 203 patients and follow-up data for 114 patients. Dialysis modality was equally distributed (49% HD and 51% aPD). Mean (SD) age was 75 ± 7 years. Fall rate was 1.00 falls/patient year, comparable in HD and aPD. Falls led to fear of falling, resulting in less activities in 68% vs 42% (p < 0.01) and leaving the house less in 59% vs 31% (p < 0.01) of patients. Patients with diabetes mellitus were twice as likely to report falls at baseline (OR 1.91 [95%CI 1.00-3.63], p = 0.05) and falls at baseline were associated with falls during follow-up (OR 2.53 [95%CI 1.06-6.04] p = 0.03). Literature revealed frailty was a strong risk factor for falling and falling results in a higher mortality and hospitalization rate. CONCLUSION: Falls were frequent in older dialysis patients and have a negative impact on quality of life. Fall incidence is comparable between aPD and HD.

Epilepsy under my skin?

A 44-year-old male patient was admitted to the hospital for observation after an unwitnessed syncope. Physical examination revealed skin purpura and bilateral tongue haematoma. Laboratory studies were unremarkable. Radiological imaging showed no abnormalities of the vasculature, signs of thrombosis or brain anomalies. Biopsy of a purpuric lesion revealed extravasation of erythrocytes. After excluding several causes of both syncope and purpura, the typical location of these thoracocervicofacial purpura, the tongue haematoma and an elevated prolactin level (which came back later) led to the diagnosis of an epileptic seizure. The patient was referred to the neurology department for follow-up. Within 3 weeks, the purpura were completely resolved, and the patient remained free of seizures during follow-up. In case of an unwitnessed syncope, an epileptic seizure should be carefully considered and thoracocervicofacial purpura can be the pivotal manifestation leading to this diagnosis.

Radiofrequency ablation is beneficial in simultaneous treatment of synchronous liver metastases and primary colorectal cancer.

BACKGROUND: In patients with resectable synchronous colorectal liver metastases (CRLM), either two-staged or simultaneous resections of the primary tumor and liver metastases are performed. Data on radiofrequency ablation (RFA) for the treatment of CRLM during a simultaneous procedure is lacking. The primary aim was to analyze short-term and long-term outcome of RFA in simultaneous treatment. A secondary aim was to compare simultaneous resection with the colorectal-first approach. METHODS: Retrospective analysis of 241 patients with colorectal cancer and synchronous CRLM between 2000-2016. Median follow-up was 36.1 months (IQR 18.2-58.8 months). A multivariable analysis was performed to analyze the postoperative morbidity, using the comprehensive complication index. A propensity matched analysis was performed to compare survival rates. RESULTS: In multivariable analysis, the best predictor of lower complication severity was treatment with RFA (p = 0.040). Higher complication rates were encountered in patients who underwent an abdominoperineal resection (p = 0.027) or age > 60 years (p = 0.022). The matched analysis showed comparable overall survival in RFA treated patients versus patients undergoing a liver resection with a five year overall survival of 39.4% and 37.5%, respectively (p = 0.782). In a second matched analysis, 5-year overall survival rates in simultaneously treated patients (43.8%) was comparable to patients undergoing the colorectal first approach (43.0%, p = 0.223). CONCLUSIONS: RFA treatment of CRLM in simultaneous procedures is associated with a lower complication severity and non-inferior oncological outcome as compared to partial liver resection. RFA should be considered a useful alternative to liver resection.

Statin use and cognitive function: population-based observational study with long-term follow-up.

We aimed to evaluate the association between statin use and cognitive function. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; low performance, 0-10; high performance, 11-12 points) in an observational study that included 4,095 community-dwelling participants aged 35-82 years. Data on statin use were obtained from a computerized pharmacy database. Analysis were done for the total cohort and subsamples matched on cardiovascular risk (N = 1232) or propensity score for statin use (N = 3609). We found that a total of 904 participants (10%) used a statin. Statin users were older than non-users: mean age (SD) 61 (10) vs. 52 (11) years (p < 0.001). The median duration of statin use was 3.8 (interquartile range, 1.6-4.5) years. Unadjusted, statin users had worse cognitive performance than non-users. The mean RFFT score (SD) in statin users and non-users was 58 (23) and 72 (26) points, respectively (p < 0.001). VAT performance was high in 261 (29%) statin users and 1351 (43%) non-users (p < 0.001). However, multiple regression analysis did not show a significant association of RFFT score with statin use (B, -0.82; 95%CI, -2.77 to 1.14; p = 0.41) nor with statin solubility, statin dose or duration of statin use. Statin users with high doses or long-term use had similar cognitive performance as non-users. This was found in persons with low as well as high cardiovascular risk, and in younger as well as older subjects. Also, the mean RFFT score per quintile of propensity score for statin use was comparable for statin users and non-users. Similar results were found for the VAT score as outcome measure. In conclusion, statin use was not associated with cognitive function. This was independent of statin dose or duration of statin use.

Longitudinal study of performance on the Ruff Figural Fluency Test in persons aged 35 years or older.

The Ruff Figural Fluency Test (RFFT) is a cognitive test to measure executive function. Longitudinal studies have shown that repeated testing improves performance on the RFFT. Such a practice effect may hinder the interpretation of test results in a clinical setting. Therefore, we investigated the longitudinal performance on the RFFT in persons aged 35-82 years. Performance on the RFFT was measured three times over an average follow-up period of six years in 2,515 participants of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study in Groningen, the Netherlands: 53% men; mean age (SD), 53 (10) years. The effect of consecutive measurements on performance on the RFFT was investigated with linear multilevel regression models that also included age, gender, educational level and the interaction term consecutive measurement number x age as independent variables. It was found that the mean (SD) number of unique designs on the RFFT increased from 73 (26) at the first measurement to 79 (27) at the second measurement and to 83 (26) at the third measurement (p<0.001). However, the increase per consecutive measurement number was negatively associated with age and decreased with 0.23 per one-year increment of age (p<0.001). The increase per consecutive measurement number was not dependent on educational level. Similar results were found for the median (IQR) number of perseverative errors which showed a small but statistically significant increase with repeating testing: 7 (3-13) at the first measurement, 7 (4-14) at the second measurement and 8 (4-15) at the third measurement (p trend = 0.002). In conclusion, the performance on the RFFT improved by repeating the test over an average follow-up period of three to six years. This practice effect was the largest in young adults and not dependent on educational level.

Pro and con arguments in using alternative dialysis regimens in the frail and elderly patients.

In the last decade, an increasing number of patients over 75 years of age are starting renal replacement therapy. Frailty is highly prevalent in elderly patients with end-stage renal disease (ESRD) in the context of the increased prevalence of some ESRD-associated conditions: protein-energy wasting, inflammation, anaemia, acidosis or hormonal disturbances. There are currently no hard data to support guidance on the optimal duration of dialysis for frail/elderly ESRD patients. The current debate is not about starting dialysis or managing conservatory frail ESRD patients, but whether a more intensive regimen once dialysis is initiated (for whatever reasons and circumstances) would improve patients' outcome. The most important issue is that all studies performed with extended/alternative dialysis regimens do not specifically address this particular type of patients and therefore all the inferences are derived from the general ESRD population. Care planning should be responsive to end-of-life needs whatever the treatment modality. Care in this setting should focus on symptom control and quality of life rather than life extension. We conclude that, similar to the general dialysed population, extensive application of more intensive dialysis schedules is not based on solid evidence. However, after a thorough clinical evaluation, a limited period of a trial of intensive dialysis could be prescribed in more problematic patients.

Serum Proenkephalin A Levels and Mortality After Long-Term Follow-Up in Patients with Type 2 Diabetes Mellitus (ZODIAC-32).

BACKGROUND: Two previous studies concluded that proenkephalin A (PENK-A) had predictive capabilities for stroke severity, recurrent myocardial infarction, heart failure and mortality in patients with stroke and myocardial infarction. OBJECTIVES: This study aimed to investigate the value of PENK-A as a biomarker for predicting mortality in patients with type 2 diabetes mellitus. METHODS: Patients with type 2 diabetes mellitus were included from the prospective observational ZODIAC (Zwolle Outpatient Diabetes project Integrating Available Care) study. The present analysis incorporated two ZODIAC cohorts (1998 and 2001). Since blood was drawn for 1204 out of 1688 patients (71%), and information on relevant confounders was missing in 47 patients, the final sample comprised 1157 patients. Cox proportional hazard models were used for evaluating the relationship between PENK-A and (cardiovascular) mortality. Risk prediction capabilities were assessed with Harrell's C statistics and the integrated discrimination improvement (IDI). RESULTS: After a follow-up period of 14 years, 525 (45%) out of 1157 patients had died, of which 224 (43%) were attributable to cardiovascular factors. Higher Log PENK-A levels were not independently associated with increased (cardiovascular) mortality. Patients with PENK-A values in the highest tertile had a 49% (95%CI 1%-121%) higher risk of cardiovascular mortality compared to patients in the reference category (lowest tertile). C-values were not different after removing PENK-A from the Cox models and there were no significant differences in IDI values. CONCLUSIONS: The associations between PENK-A and mortality were strongly attenuated after accounting for all traditional risk factors. Furthermore, PENK-A did not seem to have additional value beyond conventional risk factors when predicting all-cause and cardiovascular mortality.

Statin use and cognitive function: population-based observational study with long-term follow-up.

We aimed to evaluate the association between statin use and cognitive function. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; low performance, 0-10; high performance, 11-12 points) in an observational study that included 4,095 community-dwelling participants aged 35-82 years. Data on statin use were obtained from a computerized pharmacy database. Analysis were done for the total cohort and subsamples matched on cardiovascular risk (N = 1232) or propensity score for statin use (N = 3609). We found that a total of 904 participants (10%) used a statin. Statin users were older than non-users: mean age (SD) 61 (10) vs. 52 (11) years (p<0.001). The median duration of statin use was 3.8 (interquartile range, 1.6-4.5) years. Unadjusted, statin users had worse cognitive performance than non-users. The mean RFFT score (SD) in statin users and non-users was 58 (23) and 72 (26) points, respectively (p<0.001). VAT performance was high in 261 (29%) statin users and 1351 (43%) non-users (p<0.001). However, multiple regression analysis did not show a significant association of RFFT score with statin use (B, -0.82; 95%CI, -2.77 to 1.14; p = 0.41) nor with statin solubility, statin dose or duration of statin use. Statin users with high doses or long-term use had similar cognitive performance as non-users. This was found in persons with low as well as high cardiovascular risk, and in younger as well as older subjects. Also, the mean RFFT score per quintile of propensity score for statin use was comparable for statin users and non-users. Similar results were found for the VAT score as outcome measure. In conclusion, statin use was not associated with cognitive function. This was independent of statin dose or duration of statin use.