Evidence based cardiology - Psychosocial factors in the aetiology and prognosis of coronary heart disease: systematic review of prospective cohort studies

Summary points: In healthy populations, prospective cohort studies show a possible aetiological role for type A/hostility (6/14 studies), depression and anxiety (11/11 studies), psychosocial work characteristics (6/10 studies), social support (5/8 studies). In populations of patients with coronary heart disease, prospective studies show a prognostic role for depression and anxiety (6/6 studies), psychosocial work characteristics (1/2 studies), and social support (9/10 studies); none of five studies showed a prognostic role for type A/hostility. Although this review can not discount the possibility of publication bias, prospective cohort studies provide strong evidence that psychosocial factors, particularly depression and social support, are independent aetiological and prognostic factors for coronary heart disease

Does access to cardiac investigation and treatment contribute to social and ethnic differences in coronary heart disease? Whitehall II prospective cohort study

Objective: To determine whether access to cardiac procedures and drugs contributes to social and ethnic differences in coronary heart disease in a population setting. Design: Prospective study with follow up over 15 years. Civil service employment grade was used as a measure of individual socioeconomic position. Need for cardiac care was determined by the presence of angina, myocardial infarction, and coronary risk factors. Setting: 20 civil service departments originally located in London. Participants: 10 308 civil servants (3414 women; 560 South Asian) aged 35-55 years at baseline in 1985-8. Main outcome measures: Use of exercise electrocardiography, coronary angiography, and coronary revascularisation procedures and secondary prevention drugs. Results: Inverse social gradients existed in incident coronary morbidity and mortality. South Asian participants also had higher rates than white participants. After adjustment for clinical need, social position showed no association with the use of cardiac procedures or secondary prevention drugs. For example, men in the low versus high employment grade had an age adjusted odds ratio for angiography of 1.87 (95% confidence interval 1.32 to 2.64), which decreased to 1.27 (0.83 to 1.94) on adjustment for clinical need. South Asians tended to be more likely to have cardiac procedures and to be taking more secondary prevention drugs than white participants, even after adjustment for clinical need. Conclusion: This population based study, which shows the widely observed social and ethnic patterning of coronary heart disease, found no evidence that low social position or South Asian ethnicity was associated with lower use of cardiac procedures or drugs, independently of clinical need. Differences in medical care are unlikely to contribute to social or ethnic differences in coronary heart disease in this cohort

Recruiting patients to medical research: double blind randomised trial of "opt-in" versus "opt-out" strategies

Objective To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias. Design Double blind randomised controlled trial. Setting Two general practices in England. Participants 510 patients with angina. Intervention Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina. Main outcome measures Recruitment rate and clinical characteristics of patients. Results The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm v 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% v 60%; P = 0.053), less treatment for angina (69% v 82%; P = 0.010), and less functional impairment (9% v 20%; P = 0.023) than patients in the opt-out arm. Conclusions The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants

Organisational downsizing and musculoskeletal problems in employees: a prospective study

Objectives: To study the association between organisational downsizing and subsequent musculoskeletal problems in employees and to determine the association with changes in psychosocial and behavioural risk factors. Methods: Participants were 764 municipal employees working in Raisio, Finland before and after an organisational downsizing carried out between 1991 and 1993. The outcome measures were self reports of severity and sites of musculoskeletal pain at the end of 1993 and medically certified musculoskeletal sickness absence for 1993-5. The contribution of changes in psychosocial work characteristics and health related behaviour between the 1990 and 1993 surveys was assessed by adjustment. Results: After adjustment for age, sex, and income, the odds ratio (OR) for severe musculoskeletal pain between major and minor downsizing and the corresponding rate ratios for musculoskeletal sickness absence were 2.59 (95% confidence interval (95% CI) 1.5 to 4.5) and 5.50 (3.6 to 7.6), respectively. Differences between the mean number of sites of pain after major and minor downsizing was 0.99 (0.4 to 1.6). The largest contribution from changes in work characteristics and health related behaviour to the association between downsizing and musculoskeletal problems was from increases in physical demands, particularly in women and low income employees. Additional contributory factors were reduction of skill discretion (relative to musculoskeletal pain) and job insecurity. The results were little different when analyses were confined to initially healthy participants. Conclusions: Downsizing is a risk factor for musculoskeletal problems among those who remain in employment. Much of this risk is attributable to increased physical demands, but adverse changes in other psychosocial factors may also play a part

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Deriving research-quality phenotypes from national electronic health records to advance precision medicine: a UK Biobank case-study

High-throughput genotyping and increased availability of electronic health records (EHR) are giving scientists the unprecedented opportunity to exploit routinely generated clinical data to advance precision medicine. The extent to which national structured EHR in the United Kingdom can be utilized in genome-wide association studies (GWAS) has not been systematically examined. In this study, we evaluate the performance of an EHR-derived acute myocardial infarction phenotype (AMI) for performing GWAS in the UK Biobank

Does autonomic function link social position to coronary risk? The Whitehall II study.

BACKGROUND: Laboratory and clinical studies suggest that the autonomic nervous system responds to chronic behavioral and psychosocial stressors with adverse metabolic consequences and that this may explain the relation between low social position and high coronary risk. We sought to test this hypothesis in a healthy occupational cohort. METHODS AND RESULTS: This study comprised 2197 male civil servants 45 to 68 years of age in the Whitehall II study who were undergoing standardized assessments of social position (employment grade) and the psychosocial, behavioral, and metabolic risk factors for coronary disease previously found to be associated with low social position. Five-minute recordings of heart rate variability (HRV) were used to assess cardiac parasympathetic function (SD of N-N intervals and high-frequency power [0.15 to 0.40 Hz]) and the influence of sympathetic and parasympathetic function (low-frequency power [0.04 to 0.15 Hz]). Low employment grade was associated with low HRV (age-adjusted trend for each modality, P< or =0.02). Adverse behavioral factors (smoking, exercise, alcohol, and diet) and psychosocial factors (job control) showed age-adjusted associations with low HRV (P<0.03). The age-adjusted mean low-frequency power was 319 ms2 among those participants in the bottom tertile of job control compared with 379 ms2 in the other participants (P=0.004). HRV showed strong (P<0.001) linear associations with components of the metabolic syndrome (waist circumference, systolic blood pressure, HDL cholesterol, triglycerides, and fasting and 2-hour postload glucose). The social gradient in prevalence of metabolic syndrome was explained statistically by adjustment for low-frequency power, behavioral factors, and job control. CONCLUSIONS: Chronically impaired autonomic function may link social position to different components of coronary risk in the general population

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization.

Background: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances.Methods: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography.Results: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction - the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93) - and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend = 0.002).Conclusions: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes. (N Engl J Med 2001;344:645-54.) Copyright (C) 2001 Massachusetts Medical Society

Neutrophil Counts and Initial Presentation of 12 Cardiovascular Diseases: A CALIBER Cohort Study

BACKGROUND: Neutrophil counts are a ubiquitous measure of inflammation, but previous studies on their association with cardiovascular disease (CVD) were limited by small numbers of patients or a narrow range of endpoints. OBJECTIVES: This study investigated associations of clinically recorded neutrophil counts with initial presentation for a range of CVDs. METHODS: We used linked primary care, hospitalization, disease registry, and mortality data in England. We included people 30 years or older with complete blood counts performed in usual clinical care and no history of CVD. We used Cox models to estimate cause-specific hazard ratios (HRs) for 12 CVDs, adjusted for cardiovascular risk factors and acute conditions affecting neutrophil counts (such as infections and cancer). RESULTS: Among 775,231 individuals in the cohort, 154,179 had complete blood counts performed under acute conditions and 621,052 when they were stable. Over a median 3.8 years of follow-up, 55,004 individuals developed CVD. Adjusted HRs comparing neutrophil counts 6 to 7 versus 2 to 3 × 10(9)/l (both within the 'normal' range) showed strong associations with heart failure (HR: 2.04; 95% confidence interval [CI]: 1.82 to 2.29), peripheral arterial disease (HR: 1.95; 95% CI: 1.72 to 2.21), unheralded coronary death (HR: 1.78; 95% CI: 1.51 to 2.10), abdominal aortic aneurysm (HR: 1.72; 95% CI: 1.34 to 2.21), and nonfatal myocardial infarction (HR: 1.58; 95% CI: 1.42 to 1.76). These associations were linear, with greater risk even among individuals with neutrophil counts of 3 to 4 versus 2 to 3 × 10(9)/l. There was a weak association with ischemic stroke (HR: 1.36; 95% CI: 1.17 to 1.57), but no association with stable angina or intracerebral hemorrhage. CONCLUSIONS: Neutrophil counts were strongly associated with the incidence of some CVDs, but not others, even within the normal range, consistent with underlying disease mechanisms differing across CVDs. (White Blood Cell Counts and Onset of Cardiovascular Diseases: a CALIBER Study [CALIBER]; NCT02014610)

Technical note : an inverse method to relate organic carbon reactivity to isotope composition from serial oxidation

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 14 (2017): 5099-5114, doi:10.5194/bg-14-5099-2017.Serial oxidation coupled with stable carbon and radiocarbon analysis of sequentially evolved CO2 is a promising method to characterize the relationship between organic carbon (OC) chemical composition, source, and residence time in the environment. However, observed decay profiles depend on experimental conditions and oxidation pathway. It is therefore necessary to properly assess serial oxidation kinetics before utilizing decay profiles as a measure of OC reactivity. We present a regularized inverse method to estimate the distribution of OC activation energy (E), a proxy for bond strength, using serial oxidation. Here, we apply this method to ramped temperature pyrolysis or oxidation (RPO) analysis but note that this approach is broadly applicable to any serial oxidation technique. RPO analysis directly compares thermal reactivity to isotope composition by determining the E range for OC decaying within each temperature interval over which CO2 is collected. By analyzing a decarbonated test sample at multiple masses and oven ramp rates, we show that OC decay during RPO analysis follows a superposition of parallel first-order kinetics and that resulting E distributions are independent of experimental conditions. We therefore propose the E distribution as a novel proxy to describe OC thermal reactivity and suggest that E vs. isotope relationships can provide new insight into the compositional controls on OC source and residence time.This research was supported by the NSF Graduate Research Fellowship Program grant no. 2012126152 (Jordon D. Hemingway), NASA Astrobiology grant no. NNA13AA90A and NSF grant no. EAR-1338810 (Daniel H. Rothman), and the WHOI Independent Study Award (Valier V. Galy)