Perioperative outcome, long-term mortality and time trends in elderly patients undergoing low-, intermediate- or major non-cardiac surgery.

BACKGROUND: Decision-making whether older patients benefit from surgery can be a difficult task. This report investigates characteristics and outcomes of a large cohort of inpatients, aged 80 years and over, undergoing non-cardiac surgery. METHODS: This observational study was performed at a tertiary university medical centre in the Netherlands. Patients of 80 years or older undergoing elective or urgent surgery from January 2004 to June 2017 were included. Outcomes were length of stay, discharge destination, 30-day and long-term mortality. Patients were divided into low-, intermediate and high-risk surgery subgroups. Univariable and multivariable logistic regression were used to evaluate the association of risk factors and outcomes. Secondary outcomes were time trends, assessed with Mantel-Haenszel chi-square test. RESULTS: Data of 8251 patients, undergoing 19,027 surgical interventions were collected from the patients' medical record. 7032 primary procedures were suitable for analyses. Median LOS was 3 days in the low-risk group, compared to six in the intermediate- and ten in the high-risk group. Median LOS of the total cohort decreased from 5.8 days (IQR 1.9-14.5) in 2004-2007 to 4.6 days (IQR 1.9-9.0) in 2016-2017. Three quarters of patients were discharged to their home. Postoperative 30-day mortality in the low-risk group was 2.3%. In the overall population 30-day mortality was high and constant during the study period (6.7%, ranging from 4.2 to 8.4%). CONCLUSION: Patients should not be withheld surgery solely based on their age. However, even for low-risk surgery, the mortality rate of more than 2% is substantial. Deciding whether older patients benefit from surgery should be based on the understanding of individual risks, patients' wishes and a patient-centred plan.

Changes in demographics, treatment and outcomes in a consecutive cohort who underwent transcatheter aortic valve implantation between 2005 and 2020.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) has matured to the treatment of choice for most patients with aortic stenosis (AS). We sought to identify trends in patient and procedural characteristics, and clinical outcomes in all patients who underwent TAVI between 2005 and 2020. METHODS: A single-centre analysis was performed on 1500 consecutive patients who underwent TAVI, divided into three tertiles (T) of 500 patients treated between November 2005 and December 2014 (T1), January 2015 and May 2018 (T2) and June 2018 and April 2020 (T3). RESULTS: Over time, mean age and gender did not change (T1 to T3: 80, 80 and 79 years and 53%, 55% and 52% men, respectively), while the Society of Thoracic Surgeons risk score declined (T1: 4.5% to T3: 2.7%, p < 0.001). Use of general anaesthesia also declined over time (100%, 24% and 1% from T1 to T3) and transfemoral TAVI remained the default approach (87%, 94% and 92%). Median procedure time and contrast volume decreased significantly (186, 114 and 56 min and 120, 100 and 80 ml, respectively). Thirty-day mortality (7%, 4% and 2%), stroke (7%, 3% and 3%), need for a pacemaker (19%, 22% and 8%) and delirium (17%, 12% and 8%) improved significantly, while major bleeding/vascular complications did not change (both approximately 9%, 6% and 6%). One-year survival was 80%, 88% and 92%, respectively. CONCLUSION: Over our 15 years' experience, patient age remained unchanged but the patient risk profile became more favourable. Simplification of the TAVI procedure occurred in parallel with major improvement in outcomes and survival. Bleeding/vascular complications and the need for pacemaker implantation remain the Achilles' heel of TAVI.

Arterial stiffness is not associated with bone parameters in an elderly hyperhomocysteinemic population.

Several studies have observed positive associations between bone disease and cardiovascular disease. A potential common pathway is hyperhomocysteinemia; however, to date, there is a lack of data regarding hyperhomocysteinemic populations. Therefore, we examined both cross-sectionally and longitudinally, whether there is an association between bone parameters and arterial stiffness in a hyperhomocysteinemic population, and investigated the potential common role of homocysteine (hcy) level on these associations. Cross-sectional and longitudinal data of the B-PROOF study were used (n = 519). At both baseline and 2-year follow-up we determined bone measures-incident fractures and history of fractures, bone-mineral density (BMD) and quantitative ultrasound (QUS) measurement. We also measured arterial stiffness parameters at baseline-pulse wave velocity, augmentation index and aortic pulse pressure levels with applanation tonometry. Linear regression analysis was used to examine these associations and we tested for potential interaction of hcy level. The mean age of the study population was 72.3 years and 44.3 % were female. Both cross-sectionally and longitudinally there was no association between arterial stiffness measures and BMD or QUS measurements or with incident fractures (n = 16) within the 2-3 years of follow-up. Hcy level did not modify the associations and adjustment for hcy did not change the results. Arterial stiffness was not associated with bone parameters and fractures, and hcy neither acted as a pleiotropic factor nor as a mediator. The potential association between bone and arterial stiffness is therefore not likely to be driven by hyperhomocysteinemia.

B-vitamin levels and genetics of hyperhomocysteinemia are not associated with arterial stiffness.

BACKGROUND AND AIMS: Hyperhomocysteinemia is associated with arterial stiffness, but underlying pathophysiological mechanisms explaining this association are to be revealed. This study was aimed to explore two potential pathways concerning the one-carbon metabolism. A potential causal effect of homocysteine was explored using a genetic risk score reflecting an individual's risk of having a long-term elevated plasma homocysteine level and also associations with B-vitamin levels were investigated. METHODS AND RESULTS: Baseline cross-sectional data of the B-PROOF study were used. In the cardiovascular subgroup (n = 567, 56% male, age 72.6 ± 5.6 yrs) pulse wave velocity (PWV) was determined using applanation tonometry. Plasma concentrations of vitamin B12, folate, methylmalonic acid (MMA) and holo transcobalamin (holoTC) were assessed and the genetic risk score was based on 13 SNPs being associated with elevated plasma homocysteine. Associations were examined using multivariable linear regression analysis. B-vitamin levels were not associated with PWV. The genetic risk score was also not associated with PWV. However, the homocysteine-gene interaction was significant (p < 0.001) in the association of the genetic risk score and PWV. Participants with the lowest genetic risk of having long-term elevated homocysteine levels, but with higher measured homocysteine levels, had the highest PWV levels. CONCLUSION: Homocysteine is unlikely to be causally related to arterial stiffness, because there was no association with genetic variants causing hyperhomocysteinemia, whereas non-genetically determined hyperhomocysteinemia was associated with arterial stiffness. Moreover, the association between homocysteine and arterial stiffness was not mediated by B-vitamins. Possibly, high plasma homocysteine levels reflect an unidentified factor, that causes increased arterial stiffness.

Gait speed reference values in community-dwelling older adults - Cross-sectional analysis from the Rotterdam Study.

BACKGROUND: Gait speed is a simple, inexpensive and clinically useful marker of physical function in older adults. We aimed to establish gait speed reference values for community-dwelling older adults. To this end, we further explored the association of age, sex and height with gait speed. METHODS: This study included community-dwelling participants aged 50 years and over enrolled in the Rotterdam Study. Participants completed the gait protocol between 2009 and 2016. The mean gait speed was calculated for age and height groups, stratified by sex. Reference values for gait speed were calculated using a quantile regression model adjusted for sex, the non-linear effects of age and height, as well as the interaction between age and sex plus the interaction between age and height. RESULTS: The study population included 4656 Dutch participants with a mean (standard deviation) age of 67.7 (9.5) years, comprising 2569 (55.2%) women. The mean height of the participants was 1.69 (0.10) meters and the mean gait speed was 1.20 (0.20) m/s. Gait speed was lower with older age and greater with taller stature, but the effect of height disappeared above the age of 80 years. Sex did not affect gait speed after accounting for age and height. Age-, sex-, and height-specific reference values for gait speed are available for use at https://emcbiostatistics.shinyapps.io/GaitSpeedReferenceValues/. CONCLUSIONS: We found that height explains the commonly noted difference in usual gait speed between sexes and that neither height nor sex impacts gait speed in the very oldest adults. We developed reference values for usual gait speed in Western European community-dwelling older adults.

Metabolic syndrome detection with biomarkers in childhood cancer survivors.

PURPOSE: Augmented survival of childhood nephroblastoma and neuroblastoma has increased long-term side effects such as metabolic syndrome (MetS). Risk stratification is difficult after abdominal radiation because waist circumference underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonography. METHODS: The NCEP-ATPIII MetS-components, 14 additional serum biomarkers and 9 vascular measurements were assessed in a single-centre cohort of childhood nephroblastoma (n = 67) and neuroblastoma (n = 36) survivors and controls (n = 61). Multivariable regression models were used to study treatment effects. Principal component analysis (PCA) was used to study all biomarkers in a combined analysis, to identify patterns and correlations. RESULTS: After 27.5 years of follow-up, MetS occurred more often in survivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with several biomarker abnormalities. PCA of biomarkers revealed a pattern on PC1 from favourable lipid markers (HDL-cholesterol, adiponectin) towards unfavourable markers (triglycerides, LDL-cholesterol, apoB, uric acid). Abdominal radiotherapy was associated with the unfavourable biomarker profile (ß = 1.45, P = 0.001). Vascular measurements were not of added diagnostic value. CONCLUSIONS: Long-term childhood nephro- and neuroblastoma survivors frequently develop MetS. Additional assessment of biomarkers identified in PCA - adiponectin, LDL, apoB, and uric acid - may be used especially in abdominally irradiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasonography was not of added value.

Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease.

BACKGROUND/AIMS: Recent studies suggest that vitamin D metabolites may be important for preserving cognitive function via specific neuroprotective effects. No large studies have examined the association between vitamin D status and cognition. METHODS: In this cross-sectional study, we analyzed the serum 25-hydroxyvitamin D(3) levels and Mini-Mental State Examination (MMSE) test scores of 225 older outpatients who were diagnosed as having probable Alzheimer's disease (AD). In addition to the 25-hydroxyvitamin D(3) levels, we analyzed the serum vitamin B(1), B(6) and B(12) levels. RESULTS: An association was found between MMSE test scores and serum 25-hydroxyvitamin D(3) levels, with a beta-coefficient of 0.05 (p = 0.01). Vitamin-D-sufficient patients had significantly higher MMSE scores as compared to vitamin-D-insufficient ones. No association was found with the other serum vitamin levels. CONCLUSIONS: These data support the idea that a relationship exists between vitamin D status and cognition in patients with probable AD. However, given the cross-sectional design of this study, no causality can be concluded. Further prospective studies are needed to specify the contribution of vitamin D status to the onset and course of cognitive decline and AD.

Insertion/deletion gene polymorphism of the angiotensin-converting enzyme and blood pressure changes in older adults. The Rotterdam study.

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene may be involved in determining blood pressure changes. The aim of the present study was to assess the relationship between the ACE I/D gene and the change of blood pressure levels during follow-up. We calculated the difference between mean levels of SBP, DBP and PP obtained during the two observations as follows: BP mean levels obtained at third phase minus the BP mean levels at baseline and subsequently we investigated the association of the ACE I/D polymorphism and the mean changes of SBP, DBP and PP levels. The study was conducted within the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. Information on the II, ID and DD genotypes of the ACE gene and mean change of blood pressure levels were available in 3966 subjects. In adjusted models, subjects with the D allele had higher mean changes of systolic and pulse pressure (PP) than subjects with the I allele. The mean changes of systolic blood pressure were 6.1 (4.7-7.5), 8.2 (7.5-9.3) and 7.4 (5.9-8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The corresponding mean changes of PP through genotypes were 4.3 (3.3-5.4), 6.0 (5.3-6.7) and 5.9 (4.9-6.9) mm Hg, respectively. No difference was found for mean change of diastolic blood pressure among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with increased mean changes of systolic and PP.

TGF-beta1 polymorphisms and arterial stiffness; the Rotterdam Study.

Arterial stiffness is a risk factor for cardiovascular disease. Transforming growth factor beta1 is a pleiotropic cytokine, with many functions, including influence on the vascular wall (e.g., on angiogenesis, endothelial cells and the extracellular matrix). We investigated five functional polymorphisms in the transforming growth factor beta1 gene (-800 G/A, -509 C/T, codon 10 Leu/Pro, codon 25 Arg/Pro and codon 263 Thr/Ile) in relation to arterial stiffness in a population-based study. A total of 3863 participants of the Rotterdam Study, a prospective population-based study, were included in the current study. The relations of the genotypes and haplotypes with arterial stiffness (pulse wave velocity (PWV), distensibility coefficient (DC) and pulse pressure (PP)) were studied using analyses of variance and linear regression. The analyses were adjusted for age, sex, mean arterial pressure, heart rate, conventional cardiovascular risk factors and measures of atherosclerosis. There were no associations between PWV and -800 G/A (P=0.56), -509 C/T (P=0.29), codon 10 (P=0.98) and, codon 25 (P=0.28). These polymorphisms were not associated with the DC or with PP. The haplotype-based analyses yielded similar results. The results of this study show that the TGF-beta1 -800 G/A, -509 C/T, codon 10 Leu/Pro and codon 25 Arg/Pro polymorphisms are not associated with arterial stiffness.

Has dementia research lost its sense of reality? A descriptive analysis of eligibility criteria of Dutch dementia research protocols.

BACKGROUND/OBJECTIVES: A substantial proportion of dementia patients are excluded from research participation, while for extrapolation of the study findings, it is important that the research population represents the patient population. The aim of this study is to provide an analysis of dementia research and its exclusion criteria in order to get a clearer picture whether the research participants represent the general dementia population. METHODS: Dementia studies registered at ToetsingOnline.nl between 2006-2015 were analysed. Study characteristics, funding and eligibility criteria were described and analysed using a standardised score sheet. RESULTS: The search yielded 103 usable study protocols. The number of trials has increased over the years, and 35% of the studies were industry-financed. Alzheimer's disease was the most researched type of dementia (84%). In observational studies the most frequently observed exclusion criterion is a neurological condition, while in drug studies and other intervention studies this is a somatic condition. Of all protocols, 86% had at least one exclusion criterion concerning comorbidity. Most studies focused on mild or moderate dementia (78%). CONCLUSION: Our study has shown that the distribution of dementia research over the different subtypes of dementia does not correspond with the prevalence of these subtypes in clinical practice. The research population in the protocols is not representative of the larger patient population. A greater number of dementia patients could derive benefit from the conducted research if the research agenda were more closely aligned with disease prevalence. A better representation of all dementia patients in research will help to meet the needs of these patients.

Physical Fitness, Activity and Hand-Grip Strength Are Not Associated with Arterial Stiffness in Older Individuals.

OBJECTIVES: Whereas evidence exists about the benefits of intensive exercise on cardiovascular outcomes in older adults, data are lacking regarding long-term effects of physical fitness and physical activity on cardiovascular health. Therefore, we aimed to investigate the longitudinal association of physical fitness, physical activity and muscle strength with arterial stiffness measures. DESIGN: a longitudinal follow-up study (2 years) of data from the B-PROOF study. SETTING: a subgroup of the B-PROOF study (n=497). PARTICIPANTS: Four hundred ninety-seven participants with a mean age of 72.1 years (SD 5.4) of which 57% was male. MEASUREMENTS: All performed at baseline and after two-year follow-up. Arterial stiffness was estimated by pulse wave velocity (PWV) measured with applanation tonometry. Furthermore, augmentation index (AIx) and aortic pulse pressure (PP) were assessed. Physical activity was estimated using a validated questionnaire regarding daily activities. Physical fitness was measured with a physical performance score, resulting from a walking, chair-stand and balance test. Muscle strength was assessed with hand-grip strength using a handheld dynamometer. RESULTS: The median performance score was 9.0 [IQR 8.0-11.0], the mean physical activity was 744.4 (SD 539.4) kcal/day and the mean hand-grip strength was 33.1 (SD 10.2) kg. AIx differed between the baseline and follow-up measurement (26.2% (SD 10.1) vs. 28.1% (SD 9.9); p < 0.01), whereas PWV and aortic PP did not. In multivariable linear regression analysis, physical performance, physical activity and hand-grip strength at baseline were not associated with the amount of arterial stiffness after two years of follow-up. CONCLUSION: Physical fitness, activity and muscle strength were not associated with arterial stiffness. More research is warranted to elucidate the long-term effects of daily and intensive physical activity on arterial stiffness in an elderly population.

Does aortic stiffness improve the prediction of coronary heart disease in elderly? The Rotterdam Study.

It has been demonstrated that aortic stiffness is an independent predictor of cardiovascular disease. We investigated whether this measure is of use in cardiovascular risk stratification in clinical practice for elderly subjects (mean age 71.5 years). Within the framework of the Rotterdam Study, we stratified subjects free of coronary heart disease (CHD) at baseline into categories of low (<10%), intermediate (10-20%) and high (>20%) 10-year risk of CHD based on Framingham risk factors. Within each risk category, we determined the percentages of subjects moving into a higher or lower risk category when adding aortic stiffness to the Framingham risk factors. Among 2849 participants, 223 CHD events occurred during a median follow-up of 7.9 years. In the low risk group, 5% of the subjects could be reclassified and in the high-risk group, 6% of the subjects could be reclassified to the intermediate-risk group. In the intermediate-risk group 3% could be reclassified to the high-risk group and 6% to the low-risk group. In a population of elderly subjects, aortic stiffness measurement in addition to Framingham risk factors leads to a limited reclassification of subjects in 10-year cardiovascular disease-risk categories. Therefore, aortic stiffness is associated with the risk of CHD in elderly, but provides no additional value in cardiovascular risk stratification.

Measures of body composition and risk of heart failure in the elderly: the Rotterdam study.

OBJECTIVES: The incidence of heart failure increases with aging. Aim of the present study was to determine whether measures body composition predict incident heart failure in older adults. SETTING: Prospective community-based cohort study. 5, 868 men and women aged 55 years and older participating the Rotterdam study. Measures of body mass index and waist circumference were obtained at baseline. Information on incident heart failure was obtained during follow-up. Cox regression analyses were performed to investigate the possible association between measure of body composition and incident heart failure. RESULTS: During a mean follow up of 10.9 (SD ±4.4) years, 765 participants had heart failure. After adjustment for age and gender, 1-standard deviation of body mass index, waist circumference and the waist-hip ratio predicted heart failure (HR 1.25; 95% CI 1.17-1.34; HR 1.26; 95% CI 1.18-1.36; and HR 1.17; 95% CI 1.08-1.27), respectively. In age-stratified analyses, 1-standard deviation of body mass index (1.17; 95% CI 1.06- 1.29) and waist circumference (1.16; 95% CI 1.05- 1.29) were still associated with the risk of heart failure in the oldest participants, whereas the waist-hip ratio was not (1.06; 95% CI 0.945-1.18). CONCLUSION: Although estimates decrease with age, measures of overall and central adiposity predict incident heart failure among community dwelling older adults.