A Kiran

Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis

BACKGROUND The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences. METHOD For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates. RESULTS We identified 123 studies with 613,815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk [RR] 0·80, 95% CI 0·77-0·83), coronary heart disease (0·83, 0·78-0·88), stroke (0·73, 0·68-0·77), and heart failure (0·72, 0·67-0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84-0·91). However, the effect on renal failure was not significant (0·95, 0·84-1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend>0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I(2) statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%. INTERPRETATION Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease. FUNDING National Institute for Health Research and Oxford Martin School.

The association between hip morphology parameters and nineteen-year risk of end-stage osteoarthritis of the hip: a nested case-control study.

Objective Subtle deformities of the hip joint are implicated in the etiology of osteoarthritis (OA) of the hip. Parameters that quantify these deformities may aid understanding of these associations. We undertook this study to examine relationships between such parameters and the 19-year risk of total hip arthroplasty (THA) for end-stage OA. Methods A new software program designed for measuring morphologic parameters around the hip was developed and validated in a reliability study. THA was the outcome measure for end-stage OA. A nested case–control study was used with individuals from a cohort of 1,003 women who were recruited at year 1 in 1989 and followed up to year 20 (the Chingford Study). All hips with THA by year 20 and 243 randomly selected control hips were studied. Pelvis radiographs obtained at year 2 were analyzed for variations in hip morphology. Measurements were compared between the THA case group and the control group. Results Patients with THA had a higher prevalence of cam deformity than did their respective controls (median alpha angle 62.4° versus 45.8° [P = 0.001]; mean modified triangular index height 28.5 mm versus 26.9 mm [P = 0.001]) as well as a higher prevalence of acetabular dysplasia (mean lateral center edge angle 29.5° versus 34.3° [P = 0.001]; median extrusion index 0.25 versus 0.185 [P = 0.009]). Logistic regression analyses clustering by subject and adjusting for radiographic hip OA at year 2 showed that these morphologic parameters were still significantly associated with THA by year 20. The alpha angle and lateral center edge angle predicted the risk of THA independently when included in the same model. Conclusion This investigation describes measurements that predict the risk of THA for end-stage OA by year 20, independently of the presence of radiographic hip OA at year 2. These measurements can be made on an anteroposterior pelvis radiograph, which is an inexpensive and commonly used clinical method of investigation.

Anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced MRI.

PURPOSE To describe the anatomical distribution of synovitis and its association with joint effusion on non-enhanced and contrast-enhanced (CE) MRI in patients with knee osteoarthritis (OA). METHODS Baseline MRI was performed at 1.5T using axial proton density (PD)-weighted (w) fat suppressed (fs) and axial and sagittal T1-w fs CE sequences. Synovial enhancement was scored in nine articular subregions. Maximum synovial enhancement was grouped as absent (0), equivocal (1) and definite (2 and 3). Effusion was scored from 0 to 3 on the axial sequences. We described the anatomical distribution of synovitis, its association with effusion and compared assessment of effusion on T1-w fs CE and PD fs sequences. RESULTS 111 subjects were included and examined by MRI. 89.2% of knees exhibited at least one subregion with a minimum grade 2 and 39.6% at the maximum of a grade 3. The commonest sites for definite synovitis were posterior to the posterior cruciate ligament (PCL) in 71.2% and in the suprapatellar region in 59.5% of all knees. On T1-w fs CE, 73.0% of knees showed any effusion. Definite synovitis in at least one location was present in 96.3% knees with an effusion and in 70.0% without an effusion. Higher grades of effusion were scored on the PD fs sequence. CONCLUSION Definite synovitis was present in the majority of knees with or without effusion with the commonest sites being posterior to the PCL and in the suprapatellar recess. Joint effusion as measured on PD fs images does not only represent effusion but also synovial thickening.

What is a good patient reported outcome after total hip replacement

OBJECTIVES There is an increasing movement to collect and report patient reported outcome measures (PROMs) following total hip replacement (THR). In the UK, the procedure specific PROM of choice is the Oxford Hip Score (OHS). It is currently unclear how to use this information to determine outcome following surgery. The aim of this study was to define a threshold for the OHS that is correlated with patient satisfaction. DESIGN Prospective cohort study. SETTING A district general hospital (St. Helier Hospital, Carshalton, UK). PARTICIPANTS 799 patients receiving THR from 1995 to 2004. MAIN OUTCOME MEASURES At 12 and 24 months after surgery patients were asked if they were satisfied with surgery and completed the OHS. Receiver operating characteristic (ROC) analyses were used to identify thresholds of follow-up OHS, which best discriminated patient satisfaction. Analyses were stratified by age, sex, body mass index (BMI), baseline OHS and patient expectations. RESULTS 91.9% of patients were satisfied with THR at 12 months (92.8% at 24 months). Using the ROC technique, the OHS at 12 months associated with patient satisfaction was 38 and at 24 months 33. The OHS at 24 months associated with satisfaction was higher in those with highest tertile of baseline OHS (30, 33, 43 respectively), and lowest tertile of BMI. CONCLUSIONS We have identified a value of the OHS that predicts patient satisfaction 12-24 months following THR within a standard clinical setting. However, this threshold is markedly influenced by pre-operative OHS and should be stratified accordingly.

The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK

OBJECTIVES To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. METHODS A UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. RESULTS Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. CONCLUSIONS Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated.

The natural history of radiographic knee osteoarthritis: a fourteen-year population-based cohort study.

OBJECTIVE To establish the natural history of radiographic knee osteoarthritis (OA) over 14 years in a community-based cohort. METHODS We examined women from the Chingford Womens Study, a community-based cohort followed up for more than 14 years. We selected women for whom bilateral radiographs of the knees (with the legs in full extension) were obtained at approximately 5-year intervals. Radiographs were scored for OA in a blinded manner, using Kellgren/Lawrence (K/L) grades. Descriptive statistics and odds ratios (ORs) were used to compare the incidence, worsening, and progression of radiographic knee OA. RESULTS A complete radiography series was available for 561 of the original 1,003 subjects enrolled in the study. The median age of these subjects at baseline was 53 years (interquartile range 48-58 years). At baseline, 13.7% of the subjects had radiographic knee OA (K/L grade≥2) in at least one knee, and the prevalence increased to 47.8% by year 15. The annual cumulative incidence of radiographic knee OA was 2.3% between baseline and year 15. The annual rates of disease progression and worsening between baseline and year 15 were 2.8% and 3.0%, respectively. Subjects with a K/L grade of 1 at baseline were more likely to experience worsening by year 15 compared with subjects with a baseline grade of 0 (OR 4.5, 95% confidence interval 2.7-7.4). CONCLUSION This is the longest natural history study of radiographic knee OA to date. The results showed relatively low rates for the incidence and progression of radiographic knee OA; more than half of all subjects had no radiographic evidence of knee OA over a 15-year period of time. Subjects with a baseline K/L grade of 1 were more likely than subjects with other baseline K/L grades to experience worsening of knee OA.

Subclinical deformities of the hip are significant predictors of radiographic osteoarthritis and joint replacement in women. A 20 year longitudinal cohort study.

OBJECTIVE Femoroacetabular Impingement (FAI) and Acetabular Dysplasia are common deformities, which have been implicated as a major cause of hip osteoarthritis (OA). We examined whether these subtle deformities of the hip are associated with the development of radiographic OA and total hip replacement (THR) in women. DESIGN A population-based, longitudinal cohort of 1003 women underwent pelvis radiographs at years 2 and 20. Alpha Angle, Triangular Index Height, Lateral Centre Edge (LCE) angle and Extrusion Index were measured. An alpha angle of greater than 65° was defined as Cam-type FAI. Radiographic OA and the presence of a THR were then determined at 20 years. RESULTS Cam-type FAI was significantly associated with the development of radiographic OA. Each degree increase in alpha angle above 65° was associated with an increase in risk of 5% (Odds Ratio (OR) 1.05 [95% confidence interval (CI) 1.01-1.09]) for radiographic OA and 4% (OR 1.04 [95% CI 1.00-1.08]) for THR. For Acetabular Dysplasia, each degree reduction in LCE angle below 28° was associated with an increase in risk of 13.0% (OR 0.87 [95% CI 0.78-0.96]) for radiographic OA and 18% (OR 0.82 [95% CI 0.75-0.89]) for THR. CONCLUSIONS This study demonstrates that Cam-type FAI and mild Acetabular Dysplasia are predictive of subsequent OA and THR in a large female population cohort. These are independent of age, BMI and joint space and significantly improve current predictive models of hip OA development.

Prevalence of reported knee pain over twelve years in a community-based cohort

OBJECTIVE To describe the temporal patterns of knee pain in a community-based cohort over 12 years. METHODS Data on self-reported knee pain at 4 time points over 12 years were analyzed in participants from the Chingford Womens Study of osteoarthritis (OA) and osteoporosis. Pain status was defined as any pain in the preceding month and pain on most days in the preceding month. This status was used to classify participants according to pain patterns of asymptomatic, persistent, incident, or intermittent pain. Multinomial logistic regression was used to identify baseline predictors for each pain pattern. RESULTS Among the 489 women with complete followup data, the median age at baseline was 52 years (interquartile range [IQR] 48-58 years), the median body mass index (BMI) was 24.39 kg/m(2) (IQR 22.46-27.20), and 11.7% of the women had a Kellgren/Lawrence radiographic OA severity grade of ≥2 in at least one knee. Among subjects reporting any pain in the preceding month versus those reporting pain on most days in the preceding month, 9% versus 2% had persistent pain, 24% versus 16% had incident pain, and 29% versus 18% had intermittent pain. A higher BMI was predictive of persistent pain (odds ratio [OR] 1.14, 95% confidence interval [95% CI] 1.04-1.25) and incident pain (OR 1.10, 95% CI 1.02-1.18). The presence of radiographic knee OA was predictive of persistent pain (OR 3.70, 95% CI 1.34-10.28; P = 0.012), and reported knee injury was predictive of both persistent pain (OR 4.13, 95% CI 1.34-12.66; P = 0.013) and intermittent pain (OR 4.25, 95% CI 1.81-9.98; P = 0.001). CONCLUSION Significant variability in the temporal fluctuation of self-reported knee pain was seen in this community-based prospective study over a period of 12 years, with few women consistently reporting knee pain at each time point. Distinct baseline predictors for each pain pattern were identified and may explain the observed heterogeneity of self-reported knee pain when pain status is measured at only one time point.

Individual magnetic resonance imaging and radiographic features of knee osteoarthritis in subjects with unilateral knee pain: The health, aging, and body composition study

OBJECTIVE Strong associations between radiographic features of knee osteoarthritis (OA) and pain have been demonstrated in persons with unilateral knee symptoms. This study was undertaken to compare radiographic and magnetic resonance imaging (MRI) features of knee OA and assess their ability to discriminate between painful and nonpainful knees in persons with unilateral symptoms. METHODS The study population included 283 individuals ages 70-79 years with unilateral knee pain who were enrolled in the Health, Aging, and Body Composition Study, a study of weight-related diseases and mobility. Radiographs of both knees were read for Kellgren/Lawrence (K/L) grade and individual radiographic features, and 1.5T MRIs were assessed using the Whole-Organ Magnetic Resonance Imaging Score. The association between structural features and pain was assessed using a within-person case-control design and conditional logistic regression. Receiver operating characteristic (ROC) analysis was then used to test the discriminatory performance of structural features. RESULTS In conditional logistic analyses, knee pain was significantly associated with both radiographic features (any joint space narrowing grade ≥ 1) (odds ratio 3.20 [95% confidence interval 1.79-5.71]) and MRI features (any cartilage defect scored ≥ 2) (odds ratio 3.67 [95% confidence interval 1.49-9.04]). However, in most subjects, MRI revealed osteophytes and cartilage and bone marrow lesions in both knees, and using ROC analysis, no individual structural feature discriminated well between painful and nonpainful knees. The best-performing MRI feature (synovitis/effusion) was not significantly more informative than K/L grade ≥ 2 (P = 0.42). CONCLUSION In persons with unilateral knee pain, MRI and radiographic features were associated with knee pain, confirming that structural abnormalities in the knee have an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating between painful and nonpainful knees. Further work is needed to examine how structural and nonstructural factors influence knee pain.

Does obesity predict knee pain over fourteen years in women, independently of radiographic changes?

To examine longitudinal patterns in body mass index (BMI) over 14 years and its association with knee pain in the Chingford Study.