Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies.

BACKGROUND: Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults. METHODS: We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D. RESULTS: The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40-1.49]). The association was weaker in individuals aged ≥75 years versus 65-74 years (HR 1.32 [1.19-1.46] vs. 1.56 [1.50-1.62]; p-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85-1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59-0.98]). CONCLUSIONS: T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.

Diversity in Advance Care Planning and End-Of-Life Conversations: Discourses of Healthcare Professionals and Researchers.

To meet the end-of-life needs of all patients, ongoing conversations about values and preferences regarding end-of-life care are essential. Aspects of social identity are associated with disparities in end-of-life care outcomes. Therefore, accounting for patient diversity in advance care planning and end-of-life conversations is important for equitable end-of-life practices. We conducted 16 semi-structured interviews to explore how Dutch healthcare professionals and researchers conceptualized diversity in advance care planning and end-of-life conversations and how they envision diversity-responsive end-of-life care and research. Using thematic discourse analysis, we identified five 'diversity discourses': the categorical discourse; the diversity as a determinant discourse; the diversity in norms and values discourse; the everyone is unique discourse, and the anti-essentialist discourse. These discourses may have distinct implications for diversity-responsive end-of-life conversations, care and research. Awareness and reflection on these discourses may contribute to more inclusive end-of-life practices.

The value of ambulatory blood pressure measurement to detect masked diastolic hypotension in older patients treated for hypertension.

OBJECTIVE: assess how many patients with low ambulatory diastolic blood pressure (DBP) are not identified when relying on office DBP alone, and thus have 'masked diastolic hypotension'. DESIGN: cross-sectional, retrospective cohort study. SETTING: academic hospital. SUBJECTS: 848 patients treated for hypertension who received ambulatory blood pressure monitoring (ABPM). METHODS: cut-off value between on- and off-target systolic blood pressure (SBP): 140 mmHg. Cut-off for low office and/or ambulatory DBP: DBP ≤ 70 mmHg. 'Masked diastolic hypotension' was defined as office DBP > 70 mmHg and mean ambulatory DBP ≤ 70 mmHg. RESULTS: mean age of the sample was 60 ± 13 years, 50% was female, 37% had diabetes, 42% preexisting cardiovascular disease (CVD), mean office blood pressure (BP) was 134/79 mmHg. In all patients (n = 848), low office DBP was present in n = 84(10%), while n = 183(22%) had low ambulatory DBP. In all patients with normal-to-high office DBP (n = 764), n = 122(16%) had 'masked diastolic hypotension'. In this group, ambulatory DBP was 14-19 mmHg lower than office DBP. Patients with low ambulatory DBP were older, had more (cardiovascular) comorbidities, and used more (antihypertensive) drugs. Antihypertensive drugs were lowered or discontinued in 30% of all patients with 'masked diastolic hypotension' due to side effects. CONCLUSIONS: 'masked diastolic hypotension' is common among patients treated for hypertension, particularly in older patients with CVD (e.g. coronary artery disease, diabetes), patient groups in which the European Society of Cardiology/Hypertension guideline advises to prevent low DBP. Although it remains to be examined at which BP levels the harms of low DBP outweigh the benefits of lowering SBP, our observations are aimed to increase awareness among physicians.

Mortality Risk and Its Association with Geriatric Domain Deficits in Older Outpatients: The Amsterdam Ageing Cohort.

INTRODUCTION: In older patients, life expectancy is determined by a complex interaction of multiple geriatric domains. A comprehensive geriatric assessment (CGA) captures different geriatric domains. Yet, if and how components of the CGA are related to mortality in an outpatient geriatric setting is unknown. In the Amsterdam Ageing Cohort, we therefore studied distribution and accumulation of geriatric domain deficits in relation to mortality. METHODS: All patients received a CGA as part of standard care, independent of referral reason. We summarized deficits on the CGA, using predefined cutoffs, in 5 geriatric domains: somatic, mental, nutritional, physical, and social domain. Information on mortality was obtained from the Dutch municipal register. We used age- and sex-adjusted Cox proportional hazards analyses to relate the separate domains and accumulation of impaired domains to overall mortality. RESULTS: From the 1,055 geriatric outpatients (53% female; age 79 ± 7 years), 172 patients (16%) had died after 1.7 ± 1.1 years. In 626 patients (59%), 3 or more domains were impaired. All domains were independently associated with mortality, with the highest hazard for the somatic domain (HR 3.7 [1.7-8.0]) and the lowest hazard for the mental domain (HR 1.5 [1.1-12.0]). In addition, accumulation of impaired domains showed a gradually increased mortality risk, ranging from HR 2.2 (0.8-6.1) for 2 domains to HR 9.6 (3.7-24.7) for all 5 domains impaired. CONCLUSIONS: This study provides evidence that impairment in multiple geriatric domains is highly prevalent and independently and cumulatively associated with mortality in an outpatient geriatric setting.

Associations between gut microbiota, faecal short-chain fatty acids, and blood pressure across ethnic groups: the HELIUS study.

AIMS: Preliminary evidence from animal and human studies shows that gut microbiota composition and levels of microbiota-derived metabolites, including short-chain fatty acids (SCFAs), are associated with blood pressure (BP). We hypothesized that faecal microbiota composition and derived metabolites may be differently associated with BP across ethnic groups. METHODS AND RESULTS: We included 4672 subjects (mean age 49.8 ± 11.7 years, 52% women) from six different ethnic groups participating in the HEalthy Life In an Urban Setting (HELIUS) study. The gut microbiota was profiled using 16S rRNA gene amplicon sequencing. Associations between microbiota composition and office BP were assessed using machine learning prediction models. In the subgroups with the largest associations, faecal SCFA levels were compared in 200 subjects with lower or higher systolic BP. Faecal microbiota composition explained 4.4% of the total systolic BP variance. Best predictors for systolic BP included Roseburia spp., Clostridium spp., Romboutsia spp., and Ruminococcaceae spp. Explained variance of the microbiota composition was highest in Dutch subjects (4.8%), but very low in South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan and Turkish descent groups (explained variance <0.8%). Faecal SCFA levels, including acetate (P < 0.05) and propionate (P < 0.01), were lower in young Dutch participants with low systolic BP. CONCLUSIONS: Faecal microbiota composition is associated with BP, but with strongly divergent associations between ethnic groups. Intriguingly, while Dutch participants with lower BP had higher abundances of several SCFA-producing microbes, they had lower faecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP.

Cardiovascular risk management in rheumatoid arthritis patients still suboptimal: the Implementation of Cardiovascular Risk Management in Rheumatoid Arthritis project.

Objective: To assess the 10-year cardiovascular (CV) risk score and to identify treatment and undertreatment of CV risk factors in patients with established RA. Methods: Demographics, CV risk factors and prevalence of cardiovascular disease (CVD) were assessed by questionnaire. To calculate the 10-year CV risk score according to the Dutch CV risk management guideline, systolic blood pressure was measured and cholesterol levels were determined from fasting blood samples. Patients were categorized into four groups: indication for treatment but not treated; inadequately treated, so not meeting goals (systolic blood pressure ⩽140 mmHg and/or low-density lipoprotein ⩽2.5 mmol/l); adequately treated; or no treatment necessary. Results: A total of 720 consecutive RA patients were included, 375 from Reade and 345 from the Antonius Hospital. The mean age of patients was 59 years (s.d. 12) and 73% were female. Seventeen per cent of the patients had a low 10-year CV risk (<10%), 21% had an intermediate risk (10-19%), 53% a high risk (⩾20%) and 9% had CVD. In total, 69% had an indication for preventive treatment (cholesterol-lowering or antihypertensive drugs). Of those, 42% received inadequate treatment and 40% received no treatment at all. Conclusion: Optimal CV risk management remains a major challenge and better awareness and management are urgently needed to reduce the high risk of CVD in the RA population.

Tumour necrosis factor blocking agents and progression of subclinical atherosclerosis in patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is associated with an increased cardiovascular risk that might be due to the chronic underlying inflammatory process. We investigated whether subclinical atherosclerosis of the carotid artery in patients with AS was reduced after anti-inflammatory treatment with tumour necrosis factor (TNF) inhibitors in a prospective observational cohort study. METHODS: 67 out of 81 AS patients who used TNF inhibitors and underwent ultrasonography at baseline returned for follow-up after 4.9 years. Of all patients, 12 (15%) discontinued the use of TNF inhibitors. Assessments of medication use, AS-related factors and cardiovascular risk factors were measured at baseline and repeated at follow-up. B-mode carotid ultrasonography was used to investigate arterial wall parameters, including carotid intima-media thickness (cIMT) and Young's elastic modulus (YEM). RESULTS: After a median 4.9 years of follow-up, cIMT did not change significantly (paired t test +0.011 mm, p=0.561) in those who continued the use of TNF inhibitors, while cIMT increased substantially (+0.057 mm, p=0.069) in those who did not continue their use of TNF inhibitors. The effect of TNF inhibitors was mainly mediated by a subsequent decrease in AS disease activity. Vascular elasticity (as measured with YEM) did not change significantly in patients who discontinued TNF inhibitors or those who continued TNF inhibitors. CONCLUSIONS: The use of TNF inhibitors might stabilise or slow down the progression of subclinical atherosclerosis in AS patients, reflecting a decreased cardiovascular risk in these patients.

Cerebral small vessel disease and its relationship with all-cause mortality risk: Results from the Amsterdam Ageing cohort.

INTRODUCTION: Cerebral Small-Vessel Disease (CSVD) is a complex condition affecting the brain's vascular network, linked to cognitive and physical decline, cerebrovascular disease, and death. This study assesses the relationship between CSVD (composite and individual features) and all-cause mortality in a large cohort of geriatric outpatients. METHODS: Data from 1305 geriatric outpatients (mean age 78 ± 7; 51 % female) in the Amsterdam Ageing cohort were analysed. CSVD presence was based on brain imaging (MRI or CT), defined by a Fazekas score ≥ 2, presence of ≥1 lacunes, or (in MRI) ≥ 3 microbleeds. Mortality data (February 2016 - January 2024) was sourced from the Dutch Municipality Register. The relationship between CSVD and all-cause mortality was evaluated using a Cox proportional-hazards model, adjusting for key confounders. RESULTS: At baseline, 835 (64 %) of the 1305 patients had CSVD. During a median follow-up of 3.1 years (IQR 1.6-4.6 years), all-cause mortality was 40 % (333 patients) in the CSVD group and 26 % (121 patients) in the non-CSVD group, corresponding with incidence rates of 137 and 78 per 1000 patient-years, respectively. The age- and sex-adjusted hazard ratio for mortality in the CSVD group was 1.6 (95 % CI: 1.3-2.0). This association remained significant after adjusting for cardiovascular disease and its risk factors, physical function (gait speed), and cognitive function (MMSE). CONCLUSION: Radiographic CSVD presence is prevalent and its integration into daily care is important as it is independently linked to increased all-cause mortality in geriatric outpatients.

Infectious Diseases and Basal Ganglia Calcifications: A Cross-Sectional Study in Patients with Fahr's Disease and Systematic Review.

Background: It is unclear whether patients with basal ganglia calcifications (BGC) should undergo infectious disease testing as part of their diagnostic work-up. We investigated the occurrence of possibly associated infections in patients with BGC diagnosed with Fahr's disease or syndrome and consecutively performed a systematic review of published infectious diseases associated with BGC. Methods: In a cross-sectional study, we evaluated infections in non-immunocompromised patients aged ≥ 18 years with BGC in the Netherlands, who were diagnosed with Fahr's disease or syndrome after an extensive multidisciplinary diagnostic work-up. Pathogens that were assessed included the following: Brucella sp., cytomegalovirus, human herpesvirus type 6/8, human immunodeficiency virus (HIV), Mycobacterium tuberculosis, rubella virus, and Toxoplasma gondii. Next, a systematic review was performed using MEDLINE and Embase (2002-2023). Results: The cross-sectional study included 54 patients (median age 65 years). We did not observe any possible related infections to the BGC in this population. Prior infection with Toxoplasma gondii occurred in 28%, and in 94%, IgG rubella antibodies were present. The positive tests were considered to be incidental findings by the multidisciplinary team since these infections are only associated with BGC when congenitally contracted and all patients presented with adult-onset symptoms. The systematic search yielded 47 articles, including 24 narrative reviews/textbooks and 23 original studies (11 case series, 6 cross-sectional and 4 cohort studies, and 2 systematic reviews). Most studies reported congenital infections associated with BGC (cytomegalovirus, HIV, rubella virus, Zika virus). Only two studies reported acquired pathogens (chronic active Epstein-Barr virus and Mycobacterium tuberculosis). The quality of evidence was low. Conclusions: In our cross-sectional study and systematic review, we found no convincing evidence that acquired infections are causing BGC in adults. Therefore, we argue against routine testing for infections in non-immunocompromised adults with BGC in Western countries.

Inter-and intrarater agreement of Computed Tomographic brain calcification scoring in Primary Familial Brain Calcification.

BACKGROUND AND PURPOSE: The Total Calcification Score (TCS) is a visual rating scale to measure Primary Familial Brain Calcification (PFBC) related calcification severity on Computed Tomography (CT). We investigated the inter-and intrarater agreement of a modified TCS. MATERIALS AND METHODS: Patients aged ≥18 years with PFBC or Fahr's syndrome who visited the outpatient clinic of a Dutch academic hospital were included. The TCS was modified, for example by adding hippocampal calcification, and ranged from 0 to 95 points. Fifteen raters evaluated all CTs, of whom three evaluated the CTs twice. Their Entrustable Professional Activity (EPA) level ranged from II (medical student) to V (neuroradiologist). Agreement was assessed using the intraclass correlation coefficient (ICC) for the total score. Kendall's W and weighted Cohen's Kappa were used to determine the inter- and intrarater agreement for individual locations, respectively. RESULTS: Forty patients were included (mean age 60 years, 53% female). The median modified TCS was 34 (range 4-76). For all EPA levels, the interrater agreement of the modified TCS was excellent (ICC=0.97 (95% CI 0.95-0.98)). Kendall's W's were good to excellent for commonly affected locations, but poor to moderate for less commonly affected locations for raters with lower levels of expertise. The intrarater agreement of the modified TCS was excellent. Kappa's of most locations were substantial to almost perfect. CONCLUSIONS: The modified TCS can be used with excellent reproducibility of the overall amount of brain calcifications and with limited training, although for some individual calcification locations more expertise is needed. ABBREVIATIONS: CI, Confidence Interval; CT, Computed Tomography; EPA, Entrustable Professional Activity; IBGC, Idiopathic Basal Ganglia Calcification; ICC, Intraclass Correlation Coefficient; IQR, Interquartile Range; PFBC, Primary Familial Brain Calcification; SD, Standard Deviation, TCS, Total Calcification Score; UMCU, University Medical Center Utrecht.

Risk assessment tools for bleeding in patients with unprovoked venous thromboembolism: an analysis of the PLATO-VTE study.

BACKGROUND: Guidelines suggest indefinite anticoagulation after unprovoked venous thromboembolism (VTE) unless the bleeding risk is high, yet there is no consistent guidance on assessing bleeding risk. OBJECTIVES: This study aimed to evaluate the performance of 5 bleeding risk tools (RIETE, VTE-BLEED, CHAP, VTE-PREDICT, and ABC-Bleeding). METHODS: PLATO-VTE, a prospective cohort study, included patients aged ≥40 years with a first unprovoked VTE. Risk estimates were calculated at VTE diagnosis and after 3 months of treatment. Primary outcome was clinically relevant bleeding, as per International Society on Thrombosis and Haemostasis criteria, during 24-month follow-up. Discrimination was assessed by the area under the receiver operating characteristic curve (AUROC). Patients were classified as having a "high risk" and "non-high risk" of bleeding according to predefined thresholds; bleeding risk in both groups was compared by hazard ratios (HRs). RESULTS: Of 514 patients, 38 (7.4%) had an on-treatment bleeding. AUROCs were 0.58 (95% CI, 0.48-0.68) for ABC-Bleeding, 0.56 (95% CI, 0.46-0.66) for RIETE, 0.53 (95% CI, 0.43-0.64) for CHAP, 0.50 (95% CI, 0.41-0.59) for VTE-BLEED, and 0.50 (95% CI, 0.40-0.60) for VTE-PREDICT. The proportion of high-risk patients ranged from 1.4% with RIETE to 36.9% with VTE-BLEED. The bleeding incidence in the high-risk groups ranged from 0% with RIETE to 13.0% with ABC-Bleeding, and in the non-high-risk groups, it varied from 7.7% with ABC-Bleeding to 9.6% with RIETE. HRs ranged from 0.93 (95% CI, 0.46-1.9) for VTE-BLEED to 1.67 (95% CI, 0.86-3.2) for ABC-Bleeding. Recalibration at 3-month follow-up did not alter the results. CONCLUSION: In this cohort, discrimination of currently available bleeding risk tools was poor. These data do not support their use in patients with unprovoked VTE.

Cardiovascular comorbidities in patients with psoriatic arthritis: a systematic review.

OBJECTIVE: Data regarding cardiovascular comorbidity and cardiovascular risk factors in patients with psoriatic arthritis (PsA) are limited. To evaluate the cardiovascular risk profile, a systematic literature search was performed to provide an extensive summary of all studies available on cardiovascular risk in PsA. METHODS: Medline, EMBASE and the Cochrane library were searched from January 1966 to April 2011 for English language articles on data concerning cardiovascular diseases and cardiovascular risk factors in PsA. Review articles, case reports and studies on psoriasis alone were excluded. RESULTS: Twenty-eight articles were included in this review. Studies on all-cause mortality revealed mixed results. Available data on cardiovascular disease appeared more consistent, indicating an increased cardiovascular mortality and morbidity in PsA. Commensurate with this, surrogate markers of subclinical atherosclerosis, arterial stiffness and cardiovascular risk factors, for example hypertension, dyslipidaemia, obesity and metabolic-related factors, were more prominent in PsA compared with controls. Suppression of inflammation was linked with a favourable effect on cardiovascular surrogate markers, for example carotid intima media thickness and endothelial dysfunction, in several (un)controlled studies. CONCLUSION: Most studies point towards an increased cardiovascular risk in PsA, broadly on a par with the risk level in rheumatoid arthritis, emphasising the need for similar cardiovascular risk management in both conditions. Further studies are needed to indicate whether inflammatory suppression or modification of traditional cardiovascular risk factors, or both, will reduce cardiovascular risk.

Circulating IL-6 concentrations and associated anthropometric and metabolic parameters in South Asian men and women in comparison to European whites.

OBJECTIVE: To determine any ethnic differences in circulating interleukin (IL)-6 concentrations among SAs and Europeans, and to assess their relationship with body composition and insulin resistance measures. METHODS: Body composition was assessed among 80 SA and European men and women using anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan. Oral glucose tolerance tests with insulin response were performed to assess insulin resistance measures. IL-6 levels were measured by high sensitivity ELISA. RESULTS: Median IL-6 values were higher in SA compared with European women: 1.94 mg/l versus 1.51 mg/l, p=0.041, but not so in men (1.56 mg/l versus 1.57 mg/l). Only measures of obesity, in particular percentage fat area (r=0.6, p=0.003), were positively correlated with IL-6 in SAs. Differences in body fat percentage (visceral and total) could explain up to 30% of the IL-6 difference between Asian and European women. CONCLUSION: SA women have elevated circulating IL-6 levels, in part due to greater visceral and percent fat levels compared with European women. This observation may in part explain why Asians are at elevated cardiovascular disease risk. Future studies should address the effects of lifestyle factors (physical activity, diet) on plasma IL-6 concentrations in SA women.

The potential harm of oxygen therapy in medical emergencies.

In medical emergencies, supplemental oxygen is often administrated routinely. Most paramedics and physicians believe that high concentrations of oxygen are life-saving 1. Over the last century, however, a plethora of studies point to possible detrimental effects of hyperoxia induced by supplemental oxygen in a variety of medical emergencies. This viewpoint provides a historical overview and questions the safety of routine high-dose oxygen administration and is based on pathophysiology and (pre)clinical findings in various medical emergencies.

Prevalence of chronic diseases at the onset of inflammatory arthritis: a population-based study.

OBJECTIVE: Little is known about the presence of chronic morbidity in inflammatory arthritis (IA) patients at disease onset. Previous studies have been mainly performed in established IA patients or they focus on isolated co-morbid diseases. Our aim was to determine the prevalence of chronic diseases at the onset of IA and to determine whether this is different from the number that one might expect based on age and sex. Patients and methods. A nested case-control study from 2001 to 2010 using data from patient electronic medical records in general practice. Totally, 3354 patients with newly diagnosed IA were included. Each patient was matched on age, sex and general practice with two control patients. In total, 121 different chronic diseases were studied. RESULTS: In total, 70% of the IA patients had at least one chronic disease at the onset of IA, compared with 59% of the control patients (P < 0.001). The highest prevalence in IA patients was found for cardiovascular diseases (35%), musculoskeletal diseases (27%) and neurological diseases (22%). Compared with the control patients, patients with IA had the highest increased risk for musculoskeletal diseases [odds ratio, OR = 1.7 (95% confidence interval: 1.6-19)] and for neurological diseases [OR = 1.6 (1.4-1.7)] at the onset of IA. CONCLUSION: At the onset of IA, nearly three-quarters of patients with IA had at least one other chronic disease. Since multi-morbidity affects treatment and outcome of the IA patient, these diseases should be taken into account when treating IA patients.

Increased risk for chronic comorbid disorders in patients with inflammatory arthritis: a population based study.

BACKGROUND: Studies determining the development of a wide variety of different comorbid disorders in inflammatory arthritis (IA) patients are scarce, however, this knowledge could be helpful in optimising preventive care in IA patients. The aim of this study is to establish the risk that new chronic comorbid disorders in newly diagnosed patients with IA in a primary care setting are developed. METHODS: This is a nested-case-control study from 2001-2010 using data from electronic medical patient records in general practice. In total, 3,354 patients with newly diagnosed IA were selected. Each patient was matched with two control patients of the same age and sex in the same general practice. The development of 121 chronic comorbid disorders of index and control patients was compared using Cox regression. RESULTS: After a median follow-up period of 2.8 years, 56% of the IA-patients had developed at least one chronic comorbid disorder after the onset of IA, compared to 46% of the control patients (p < 0.05). The most frequent developed comorbid disorders after the onset of IA were of cardiovascular (23%), and musculoskeletal (17%) origin. The highest hazard ratios (HRs) were found for anaemia (HR 2.0 [95% CI: 1.4-2.7]) osteoporosis (HR 1.9 [1.4-2.4]), and COPD (HR 1.8 [1.4-2.3]). CONCLUSION: Patients with IA developed more chronic comorbid disorders after the onset of IA than one might expect based on age and sex. Since comorbidity has a large impact on the disease course, quality of life, and possibly on treatment itself, prevention of comorbidity should be one of the main targets in the treatment of IA patients.

[Cardiovascular risk factors from an aging perspective]. / Zijn de risicofactoren voor een coronaire hartziekte leeftijdsafhankelijk?

There is a clear increase in cardiovascular risk with increasing age. However, in relative terms the contribution of individual cardiovascular risk factors such as BMI or blood pressure to the occurrence of cardiovascular disease weakens with age. Whether these weaker associations are causal or driven by other confounding factors is unclear. If such associations are indeed causal, this would imply that cardiovascular risk factors require less intensive treatment with ageing. A recent study using mendelian randomization techniques confirmed that the causal relationship of cardiovascular risk factors with the occurrence of coronary artery disease weakens with age. In this article we discuss the possible contribution of mendelian randomization studies in studying casual relationships between cardiovascular risk factors and cardiovascular disease. We also comment on what the possible consequences are for cardiovascular risk management in older people in daily clinical practice.

Ectopic Calcification: What Do We Know and What Is the Way Forward?

Ectopic calcification, or ectopic mineralization, is a pathologic condition in which calcifications develop in soft tissues [...].