Multisite pain and self-reported falls in older people: systematic review and meta-analysis.

BACKGROUND: Multisite pain and falls are common in older people, and isolated studies have identified multisite pain as a potential falls risk factor. This study aims to synthesise published literature to further explore the relationship between multisite pain and falls and to quantify associated risks. METHODS: Bibliographic databases were searched from inception to December 2017. Studies of community-dwelling adults aged 50 years and older with a multisite pain measurement and a falls outcome were included. Two reviewers screened articles, undertook quality assessment and extracted data. Random-effects meta-analysis was used to pool the effect estimate (odds ratio (OR) and 95% confidence interval (95%CI)). Heterogeneity was assessed by I2; sensitivity analyses used adjusted risk estimates and exclusively longitudinal studies. RESULTS: The search identified 49,577 articles, 3145 underwent abstract review, 22 articles were included in the systematic review and 18 were included in the meta-analysis. The unadjusted pooled OR of 1.82 (95%CI 1.55-2.13), demonstrating that those reporting multisite pain are at increased risk of falls, is supported by the adjusted pooled OR of 1.56 (95%CI 1.39-1.74). Multisite pain predicts future falls risk (OR = 1.74 (95%CI 1.57-1.93)). For high-quality studies, those reporting multisite pain have double the odds of a future fall compared to their pain-free counterparts. CONCLUSION: Multisite pain is associated with an increased future falls risk in community-dwelling older people. Increasing public awareness of multisite pain as a falls risk factor and advising health and social care professionals to identify older people with multisite pain to signpost accordingly will enable timely falls prevention strategies to be implemented

Interstitial lung disease is a risk factor for ischaemic heart disease and myocardial infarction.

OBJECTIVES: Despite many shared risk factors and pathophysiological pathways, the risk of ischaemic heart disease (IHD) and myocardial infarction (MI) in interstitial lung disease (ILD) remains poorly understood. This lack of data could be preventing patients who may benefit from screening for these cardiovascular diseases from receiving it. METHODS: A population-based cohort study used electronic patient records from the Clinical Practice Research Datalink and linked Hospital Episode Statistics to identify 68 572 patients (11 688 ILD exposed (mean follow-up: 3.8 years); 56 884 unexposed controls (mean follow-up: 4.0 years), with 349 067 person-years of follow-up. ILD-exposed patients (pulmonary sarcoidosis (PS) or idiopathic pulmonary fibrosis (PF)) were matched (by age, sex, registered general practice and available follow-up time) to patients without ILD or IHD/MI. Rates of incident MI and IHD were estimated. HRs were modelled using multivariable Cox proportional hazards regression accounting for potential confounders. RESULTS: ILD was independently associated with IHD (HR 1.85, 95% CI 1.56 to 2.18) and MI (HR 1.74, 95% CI 1.44 to 2.11). In all disease categories, risk of both IHD and MI peaked between ages 60 and 69 years, except for the risk of MI in PS which was greatest <50 years. Men with PF were at greatest risk of IHD, while women with PF were at greatest risk of MI. CONCLUSIONS: ILD, particularly PF, is independently associated with MI and IHD after adjustment for established cardiovascular risk factors. Our results suggest clinicians should prioritise targeted assessment of cardiovascular risk in patients with ILD, particularly those aged 60-69 years. Further research is needed to understand the impact of such an approach to risk management

Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.

BACKGROUND: Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ("unattributed" chest pain) but are at increased risk of cardiovascular events. AIM: To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model. METHODS: The study used UK primary care electronic health records from the Clinical Practice Research Datalink (CPRD) linked to admitted hospitalisations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. RESULTS: There were 374,917 patients with unattributed chest pain in the development dataset. Strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk. CONCLUSION: Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Increased cardiovascular mortality associated with gout: a systematic review and meta-analysis

BACKGROUND: Hyperuricaemia, the biochemical precursor to gout, has been shown to be an independent risk factor for mortality from cardiovascular disease (CVD), although studies examining the clinical phenomenon of gout and risk of CVD mortality report conflicting results. This study aimed to produce a pooled estimate of risk of mortality from cardiovascular disease in patients with gout. DESIGN: Systematic review and meta-analysis. METHODS: Electronic bibliographic databases were searched from inception to November 2012, with results reviewed by two independent reviewers. Studies were included if they reported data on CVD mortality in adults with gout who were free of CVD at time of entry into the study. Pooled hazard ratios (HRs) for this association were calculated both unadjusted and adjusted for traditional vascular risk factors. RESULTS: Six papers, including 223,448 patients, were eligible for inclusion (all (CVD) mortality n = 4, coronary heart disease (CHD) mortality n = 3, and myocardial infarction mortality n = 3). Gout was associated with an excess risk of CVD mortality (unadjusted HR 1.51 (95% confidence interval, CI, 1.17-1.84)) and CHD mortality (unadjusted HR 1.59, 95% CI 1.25-1.94)). After adjusting for traditional vascular risk factors, the pooled HR for both CVD mortality (HR 1.29, 95% CI 1.14-1.44) and CHD mortality (HR 1.42, 95% CI 1.22-1.63) remained statistically significant, but none of the studies reported a significant association with myocardial infarction. CONCLUSIONS: Gout increases the risk of mortality from CVD and CHD, but not myocardial infarction, independently of vascular risk factors

Increased risk of vascular disease associated with gout: a retrospective, matched cohort study in the UK Clinical Practice Research Datalink.

OBJECTIVES: To determine whether gout increases risk of incident coronary heart disease (CHD), cerebrovascular (CVD) and peripheral vascular disease (PVD) in a large cohort of primary care patients with gout, since there have been no such large studies in primary care. METHODS: A retrospective cohort study was performed using data from the Clinical Practice Research Datalink (CPRD). Risk of incident CHD, CVD and PVD was compared in 8386 patients with an incident diagnosis of gout, and 39 766 age, sex and registered general practice-matched controls, all aged over 50 years and with no prior vascular history, in the 10 years following incidence of gout, or matched index date (baseline). Multivariable Cox Regression was used to estimate HRs and covariates included sex and baseline measures of age, Body Mass Index, smoking, alcohol consumption, Charlson comorbidity index, history of hypertension, hyperlipidaemia, chronic kidney disease, statin use and aspirin use. RESULTS: Multivariable analysis showed men were at increased risk of any vascular event (HRs (95% CIs)) HR 1.06 (1.01 to 1.12), any CHD HR 1.08 (1.01 to 1.15) and PVD HR 1.18 (1.01 to 1.38), while women were at increased risk of any vascular event, HR 1.25 (1.15 to 1.35), any CHD HR 1.25 (1.12 to 1.39), and PVD 1.89 (1.50 to 2.38)) but not any CVD. CONCLUSIONS: In this cohort of over 50s with gout, female patients with gout were at greatest risk of incident vascular events, even after adjustment for vascular risk factors, despite a higher prevalence of both gout and vascular disease in men. Further research is required to establish the reason for this sex difference