Depression as a Risk Factor for the Initial Presentation of Twelve Cardiac, Cerebrovascular, and Peripheral Arterial Diseases: Data Linkage Study of 1.9 Million Women and Men

BACKGROUND: Depression is associated with coronary heart disease and stroke, but associations with a range of pathologically diverse cardiovascular diseases are not well understood. We examine the risk of 12 cardiovascular diseases according to depression status (history or new onset). METHODS: Cohort study of 1,937,360 adult men and women, free from cardiovascular disease at baseline, using linked UK electronic health records between 1997 and 2010. The exposures were new-onset depression (a new GP diagnosis of depression and/or prescription for antidepressants during a one-year baseline), and history of GP-diagnosed depression before baseline. The primary endpoint was initial presentation of 12 cardiovascular diseases after baseline. We used disease-specific Cox proportional hazards models with multiple imputation adjusting for cardiovascular risk factors (age, sex, socioeconomic status, smoking, blood pressure, diabetes, cholesterol). RESULTS: Over a median [IQR] 6.9 [2.1-10.5] years of follow-up, 18.9% had a history of depression and 94,432 incident cardiovascular events occurred. After adjustment for cardiovascular risk factors, history of depression was associated with: stable angina (Hazard Ratio = 1.38, 95%CI 1.32-1.45), unstable angina (1.70, 1.60-1.82), myocardial infarction (1.21, 1.16-1.27), unheralded coronary death (1.23, 1.14-1.32), heart failure (1.18, 1.13-1.24), cardiac arrest (1.14, 1.03-1.26), transient ischemic attack (1.31, 1.25-1.38), ischemic stroke (1.26, 1.18-1.34), subarachnoid haemorrhage (1.17, 1.01-1.35), intracerebral haemorrhage (1.30, 1.17-1.45), peripheral arterial disease (1.24, 1.18-1.30), and abdominal aortic aneurysm (1.12,1.01-1.24). New onset depression developed in 2.9% of people, among whom 63,761 cardiovascular events occurred. New onset depression was similarly associated with each of the 12 diseases, with no evidence of stronger associations compared to history of depression. The strength of association between depression and these cardiovascular diseases did not differ between women and men. CONCLUSION: Depression was prospectively associated with cardiac, cerebrovascular, and peripheral diseases, with no evidence of disease specificity. Further research is needed in understanding the specific pathophysiology of heart and vascular disease triggered by depression in healthy populations

Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disease: A Population Record-Linkage Cohort Study in England

Introduction: While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD), our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range. Methods: CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models. Results: The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR]=1.43, 95%CI 1.21-1.70), unheralded coronary death (IRR=1.60, 95%CI 1.18-2.18), heart failure (IRR=1.61, 95%CI 1.43-1.83), cardiac arrest (HR=2.1626, 95%CI 1.69-3.02) and peripheral arterial disease (HR=1.36, 95%CI 1.14-1.62); and lower rates of stable angina (HR=0.83, 95%CI 0.73-0.95). There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age. Conclusions: The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis

Nuclear Grade Plus Proliferation Grading System for Invasive Ductal Carcinoma of the Breast Validation in a Tertiary Referral Hospital Cohort

Objectives: For patients with invasive breast cancer, management decisions are informed by tumor grade according to the Nottingham Grading System (NGS), either on its own or as part of the Nottingham Prognostic Index (NPI). A system retaining the nuclear grade element but substituting the two subjective components, mitosis count and tubule formation, of the NGS with a proliferation index based on Ki-67 (MIB-1) has been proposed (nuclear grade plus proliferation [N+P] grading). Methods: We validated the prognostic value of this grading system on a population of 322 women. Results: N+P grading resulted in more grade I tumors (47.9% vs 4.5%) and fewer grade II (32% vs 51.5%) and grade III (20.1% vs 44%) tumors compared with NGS. The NPI calculated based on N+P grade had a similar association with survival (P < .001; odds ratio, 1.729) as the NPI calculated on the basis of the NGS grade (P < .001; odds ratio, 1.668). Conclusions: The N+P system seems equivalent to the NGS system

Study flow diagram.

<p>Note: CVD, cardiovascular disease; RA, rheumatoid arthritis; SID, supportive information for rheumatoid arthritis diagnosis.</p

Incidence of the initial presentation of twelve cardiovascular diseases with 95% confidence interval in individuals with and without rheumatoid arthritis.

<p>Incidence of the initial presentation of twelve cardiovascular diseases with 95% confidence interval in individuals with and without rheumatoid arthritis.</p

Characteristics^* of individuals with and without rheumatoid arthritis.

<p>Characteristics^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151245#t001fn002" target="_blank">*</a>} of individuals with and without rheumatoid arthritis.</p

Socioeconomic Deprivation and the Incidence of 12 Cardiovascular Diseases in 1.9 Million Women and Men: Implications for Risk Prediction and Prevention

<div><p>Background</p><p>Recent experimental evidence suggests that socioeconomic characteristics of neighbourhoods influence cardiovascular health, but observational studies which examine deprivation across a wide range of cardiovascular diseases (CVDs) are lacking.</p><p>Methods</p><p>Record-linkage cohort study of 1.93 million people to examine the association between small-area socioeconomic deprivation and 12 CVDs. Health records covered primary care, hospital admissions, a myocardial infarction registry and cause-specific mortality in England (CALIBER). Patients were aged ≥30 years and were initially free of CVD. Cox proportional hazard models stratified by general practice were used.</p><p>Findings</p><p>During a median follow-up of 5.5 years 114,859 people had one of 12 initial CVD presentations. In women the hazards of all CVDs except abdominal aortic aneurysm increased linearly with higher small-area socioeconomic deprivation (adjusted HR for most vs. least deprived ranged from 1.05, 95%CI 0.83–1.32 for abdominal aortic aneurysm to 1.55, 95%CI 1.42–1.70 for heart failure; I² = 81.9%, τ² = 0.01). In men heterogeneity was higher (HR ranged from 0.89, 95%CI 0.75–1.06 for cardiac arrest to 1.85, 95%CI 1.67–2.04 for peripheral arterial disease; I² = 96.0%, τ² = 0.06) and no association was observed with stable angina, sudden cardiac death, subarachnoid haemorrhage, transient ischaemic attack and abdominal aortic aneurysm. Lifetime risk difference between least and most deprived quintiles was most marked for peripheral arterial disease in women (4.3% least deprived, 5.8% most deprived) and men (4.6% least deprived, 7.8% in most deprived); but it was small or negligible for sudden cardiac death, transient ischaemic attack, abdominal aortic aneurysm and ischaemic and intracerebral haemorrhage, in both women and men.</p><p>Conclusions</p><p>Associations of small-area socioeconomic deprivation with 12 types of CVDs were heterogeneous, and in men absent for several diseases. Findings suggest that policies to reduce deprivation may impact more strongly on heart failure and peripheral arterial disease, and might be more effective in women.</p></div

Hazard ratios for the association between the initial presentation of 12 cardiovascular diseases and socioeconomic deprivation (ref. least deprived quintile) adjusted for common cardiovascular risk factors measured at baseline in women.

<p>Hazard ratios for the association between the initial presentation of 12 cardiovascular diseases and socioeconomic deprivation (ref. least deprived quintile) adjusted for common cardiovascular risk factors measured at baseline in women.</p

Increment in c-index associated with inclusion of socioeconomic deprivation in cardiovascular phenotype specific models containing age in women.

<p>Increment in c-index associated with inclusion of socioeconomic deprivation in cardiovascular phenotype specific models containing age in women.</p

Baseline patient characteristics by quintile of small-area socioeconomic deprivation in men and women.

<p>Note: BMI, body mass index; DBP, diastolic blood pressure; HDL, high density lipoprotein; SD; standard deviation; SBP, systolic blood pressure; Q, quintile of social deprivation.</p><p>*Missing values for ethnicity = 47.4%; hypertension = 50.2%; obesity and BMI = 69.5%; SBP and DBP = 57.5%.</p