Impact of hospitalisation on behavioural and physiological stress responses associated with cardiovascular risk in visiting family members.

BACKGROUND: The hospitalisation of a patient in intensive care impacts the psychological health of family members, with a high prevalence of anxiety, depression, and post-traumatic stress symptoms reported among families of critically ill patients. Understanding of the behavioural and physiological impact is limited and presents a new area of focus. OBJECTIVES: The objective of this study was to evaluate behavioural and physiological stress responses of visiting family members following hospitalisation of their adult relative. METHODS: Prospective longitudinal evaluation included 40 family members of adult patients with admission to intensive or coronary care in a large tertiary care metropolitan hospital. Assessments were conducted at three timepoints: in-hospital within 1 week of admission and 2 weeks and 3 months post discharge. Assessments included duration and quality of sleep (self-reported and actigraphy measured), physical activity, dietary and alcohol patterns, resting heart rate and blood pressure, and morning blood cortisol and lipid levels. Assessment of a reference group of 40 non-hospital-exposed control participants was also conducted. RESULTS: At the in-hospital assessment, study participants reported lower sleep time, altered 24-h physical activity patterns, reduced dietary and alcohol intake, and higher systolic and diastolic blood pressure than a nonhospitalised reference group. Compared to in-hospital assessment, these altered behavioural and physiological responses improved over time except for systolic blood pressures which remained unchanged at 3 months post family member discharge. CONCLUSION: Hospitalisation is associated with altered behavioural and physiological responses in family members. These findings contribute to understanding of the impact of unexpected hospitalisation on family members' cardiovascular risk factors and provide insights into potential mechanisms for the proposed increased risk during this time. Elevated systolic blood pressure at 3 months post discharge suggests a prolonged cardiovascular stress response in many family members of critical care patients that requires further study, with a focus on contributing and potential modifiable factors.

Masters age football and cardiovascular risk.

BACKGROUND: Football (soccer) is popular among those of Masters age (≥35 years). Although regular exercise improves health, strenuous exercise causes a transient increase in cardiac risk. AIM: To gain insight into cardiac risk factors, symptoms, and knowledge, attitudes and beliefs about myocardial infarction (MI), and support for prevention. METHODS: A web-based survey using REDCap was completed by 153 amateur Masters footballers from A grade competition (n = 24), B or lower grade (n = 95) or social games (n = 34) in Sydney, Australia. RESULTS: Participants were aged 49.3 ± 7.5 years and primarily male (92.2%), Caucasian (88.9%) and university educated (75.2%). Risk factors included hypercholesterolaemia (37.3%), hypertension (19.6%), smoker (7.8%), overweight (40.5%) or obese (13.1%). One-fifth (21.6%) reported ≥1 potential cardiac symptom during activity in the prior year, for which one-quarter (24.2%) sought medical attention. Knowledge of typical MI symptoms was high (>80%) but lower (<40%) for less typical symptoms. Half (49.6%) were not confident to recognise MI in themselves. Half (49.0%) would remain on the field for 5-10 min with chest pain. Only 39.9% were aware that warning signs might precede MI by days. They overestimated survival from cardiac arrest (43%). Participants supported training in automatic external defibrillators (AED) and cardiopulmonary resuscitation (84%), AED at games (85%) and cardiac education (>70%). CONCLUSIONS: Cardiac risk factors are common In Masters footballers, with one in five experiencing possible cardiac symptoms in the prior year. While gaps exist in knowledge and optimal responses, strong support exists for preventive measures.

A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology.

Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary analysis included all 9 studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using small-interfering RNA and then measuring F7 messenger RNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke (IS), and venous thromboembolism. We identified 2 novel (REEP3 and JAZF1-AS1) and 6 known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, whereas silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of IS. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of IS in the general population.

Psychological responses and coping behaviour of visiting family members during and following unplanned hospital admission.

AIMS: To describe the psychological symptoms and coping behaviours of visiting family members following the unplanned hospitalisation of their relative. BACKGROUND: Hospitalisation of a patient is recognised as a stressful time for visiting family members, who experience psychological morbidity and elevated health risk. DESIGN: This prospective longitudinal evaluation included 40 family members of patients with unplanned admission to coronary or intensive care. Assessments were conducted at 3 timepoints: in-hospital within 1 week of admission and again at 2 weeks and 3 months post-discharge. Measures included symptoms of anxiety, depression, and anger, coping strategies and social support. This paper adhered to STROBE guidelines. RESULTS: At the initial in-hospital assessment study participants reported higher anxiety, depression and anger symptoms levels compared to community matched control participants. Compared to in-hospital assessment, anxiety and depression levels were lower at 2 weeks and 3 months following hospital discharge. The use of active coping and the use of religion during early hospitalisation were associated with higher anxiety and depression symptoms at 3 months post-discharge. Conversely, use of instrumental support (getting help and advice from others), planning and venting during early hospitalisation were associated with lower depression symptoms at 3 months. Venting during the hospitalisation period was also associated with lower anxiety symptoms at 3 months. CONCLUSION: Results demonstrate the significant psychological impact of unplanned hospitalisation on visiting family members both during and following hospitalisation. The finding that prolonged psychological response is associated with individual coping strategies employed in the early hospitalised period informs potential preventative approaches for family members at risk of prolonged psychological morbidity following hospitalisation of their loved one. RELEVANCE TO CLINICAL PRACTICE: The reported psychological impact of hospitalisation on family members provides a strong imperative for nurses and health professionals to provide early individualised support to reduce the risk of long-term psychological morbidity.

Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.

BACKGROUND: Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF. METHODS: We meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events. RESULTS: We identified 13 novel genome-wide significant ( P≤2.5×10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk. CONCLUSIONS: The meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.

The effect of metoprolol and aspirin on cardiovascular risk in bereavement: A randomized controlled trial.

BACKGROUND: Bereavement is associated with an increased risk of cardiovascular disease; however, no reports exist of interventions to reduce risk. In a randomized, double-blind, placebo-controlled trial of 85 recently bereaved participants, we determined whether ß-blocker (metoprolol 25 mg) and aspirin (100 mg) reduce cardiovascular risk markers and anxiety, without adversely affecting bereavement intensity. METHODS: Participants were spouses (n = 73) or parents (n = 12) of deceased from 5 hospitals in Sydney, Australia, 55 females, 30 males, aged 66.1 ±â€¯9.4 years. After assessment within 2 weeks of bereavement, subjects were randomized to 6 weeks of daily treatment or placebo, and the effect evaluated using ANCOVA, adjusted for baseline values (primary analysis). RESULTS: Participants on metoprolol and aspirin had lower levels of home systolic pressure (P = .03), 24-hour average heart rate (P < .001) and anxiety (P = .01) platelet response to arachidonic acid (P < .001) and depression symptoms (P = .046) than placebo with no difference in standard deviation of NN intervals index (SDNNi), von Willebrand Factor antigen, platelet-granulocyte aggregates or bereavement intensity. No significant adverse safety impact was observed. CONCLUSIONS: In early bereavement, low dose metoprolol and aspirin for 6 weeks reduces physiological and psychological surrogate measures of cardiovascular risk. Although further research is needed, results suggest a potential preventive benefit of this approach during heightened cardiovascular risk associated with early bereavement.

Triggering of Acute Coronary Occlusion by Episodes of Vigorous Physical Exertion.

BACKGROUND: There is increasing recognition that heavy exertion can occasionally trigger an acute myocardial infarction (MI), although some uncertainties exist regarding the link. The primary aim of this study was to compare the relative risk (RR) of MI following vigorous exertion between those with confirmed coronary occlusion and those with a non-occluded culprit artery on acute angiography. Secondary aims were to determine if the risk of coronary occlusion is modified by the type of exercise (dynamic or isometric resistance), the frequency of regular exertion or whether the exertion was emotionally charged. METHODS: Seven hundred sixty-two (762) participants with MI (410 with coronary occlusion TIMI 0,1), and 352 (46%) with a non-occluded culprit artery (TIMI 2,3) completed a questionnaire within 4days of admission, detailing episodes of physical exertion in the 28hours prior to symptom onset and the usual frequency of such exertion. Exertion exposures within 1hour prior to symptom onset were compared to subjects' usual yearly exposure, with case-crossover methodology. RESULTS: The RR of symptom onset following heavy physical exertion level ≥6 (exertion scale 1-8), was higher in those with TIMI 0,1 compared to those with TIMI 2,3 flow (RR 6.30, 95% CI 4.70-8.50 vs 3.93, 2.89-5.30). The increased risk of coronary occlusion following vigorous exertion was observed following both dynamic exertion and isometric resistance, and did not differ between exertion types. The highest risk of coronary occlusion following exertion was observed in those who were sedentary (regular vigorous exertion <1day weekly) (RR=77, 95% CI 46-132), whereas in those who frequently perform regular vigorous physical exertion (>4days weekly), the RR of symptom onset during exertion was significantly lower, RR 2.3 (95% CI 1.5-3.6). There was no significant difference in relative risk based on whether the exertion was reported as emotionally charged. CONCLUSIONS: The relative risk that heavy exertion will trigger a non-fatal MI with an occluded artery is greater than for a non-occluded culprit artery. Both dynamic and isometric exertion increase the relative risk of event, while exposure to regular vigorous exertion reduces the relative risk.

Triggering of acute myocardial infarction by respiratory infection.

BACKGROUND: Respiratory infection has been associated with an increased short-term risk of myocardial infarction (MI). However, previous studies have predominantly been conducted without angiographic confirmation of MI. The possibility can therefore not be excluded that raised troponin levels or electrocardiogram abnormalities that may be seen with respiratory infections are due to non-ischaemic causes. AIMS: To investigate the association between respiratory infection and angiographically confirmed MI. METHODS: Interviews were conducted within 4 days of hospitalisation in 578 patients with angiographically confirmed MI, to assess for recent exposure to respiratory infection symptoms and the usual annual frequency of these symptoms. Using case-crossover methodology, exposure to respiratory infection prior to the onset of MI was compared against the usual frequency of exposure in the past year. RESULTS: Symptoms of respiratory infection were reported by 100 (17%) and 123 (21%) within 7 and 35 days, respectively, prior to MI. The relative risk (RR) for MI occurring within 1-7 days after respiratory infection symptoms was 17.0 (95% confidence interval (CI) 13.2-21.8), and declined with subsequent time periods. In a subgroup analysis, the RR tended to be lower in groups taking regular cardiac medications. For those who reported milder, upper respiratory tract infection symptoms, the RR for the 1-7-day time period was 13.5 (95% CI 10.2-17.7). CONCLUSION: These findings confirm that respiratory infection can trigger MI. Further study is indicated to identify treatment strategies to decrease this risk, particularly in individuals who may have increased susceptibility.

The impact of hospitalisation on a visiting family member: A case study and discussion.

Evidence suggests that when an immediate family member of a spouse is hospitalised, the partner's risk of death significantly increases. Hospitalisation can represent a time of great vulnerability and imposed stress for both the patient and their family members. Family members have been reported to give priority to the welfare of their ill relative and in their heightened emotional state, often adversely put their own health at risk. The paper presents a case study highlighting how an intensive care hospitalisation and discharge to rehabilitation experience for a patient's mother triggered an episode of myocardial infarction for her adult son. Discussion focuses on the caregiving burden and potential mechanisms for how hospitalisation may contribute to the health risk of immediate family members of hospitalised patients. Discussion also highlights the importance of family members receiving clear, continuous and consistent information from a limited number of clinicians to help reduce the stress associated with caregiving during acute hospitalisation.

The effect of omega-3 polyunsaturated fatty acids on fibrin and thrombin generation in healthy subjects and subjects with cardiovascular disease.

Hypercoagulability plays a key role in the progression of cardiovascular disease (CVD). Although omega-3 polyunsaturated fatty acid (PUFA) intake has been inversely related to the risk of cardiovascular events, the mechanisms are not fully understood. The aim of this study was to investigate the effects of omega-3 on novel markers of global coagulation. The generation of fibrin and thrombin, measured via overall hemostasis potential (OHP) assay and calibrated automated thrombography, respectively, was determined in 40 healthy subjects and 16 patients with CVD at baseline and after 4 weeks of 640 mg/day omega-3 PUFA. In healthy subjects, fibrin generation was significantly reduced, as measured by overall coagulation potential (p = 0.013), OHP (p < 0.001), velocity of fibrin polymerization (p = 0.002), and significant increase in delay to fibrin generation (p = 0.002). The peak of generated thrombin was significantly reduced (p = 0.043). In subjects with CVD, omega-3 PUFA significantly reduced OHP and significantly increased the lag time to thrombin generation (both p < 0.001). Treatment with omega-3 PUFA had no effect on other fibrin and thrombin generation parameters in CVD patients. Four-week omega-3 PUFA supplementation reduced thrombotic potential in healthy subjects, as shown by reduced fibrin generation and peak thrombin. There was a greater effect on fibrin generation in healthy subjects compared with those with CVD.

Risk of myocardial infarction immediately after alcohol consumption.

BACKGROUND: Habitual moderate alcohol consumption is associated with a lower risk of acute myocardial infarction (MI), whereas heavy (binge) drinking is associated with higher cardiovascular risk. However, less is known about the immediate effects of alcohol consumption on the risk of acute MI and whether any association differs by beverage type or usual drinking patterns. METHODS: We conducted a case-crossover analysis of 3869 participants from the Determinants of Myocardial Infarction Onset Study who were interviewed during hospitalization for acute MI in one of the 64 medical centers across the United States in 1989-1996. We compared the observed number of times that each participant consumed wine, beer, or liquor in the hour preceding MI symptom onset with the expected frequency based on each participant's control information, defined as the number of times the participant consumed alcohol in the past year. RESULTS: Among 3869 participants, 2119 (55%) reported alcohol consumption in the past year, including 76 within 1 hour before acute MI onset. The incidence rate of acute MI onset was elevated 1.72-fold (95% confidence interval [CI] = 1.37-2.16) within 1 hour after alcohol consumption. The association was stronger for liquor than for beer or wine. The higher rate was not apparent for daily drinkers. For the 24 hours after consumption, there was a 14% lower rate (relative risk = 0.86 [95% CI = 0.79-0.95]) of MI compared with periods with no alcohol consumption. CONCLUSIONS: Alcohol consumption is associated with an acutely higher risk of MI in the subsequent hour among people who do not typically drink alcohol daily.

Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans.

Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII :C) and VWF antigen (VWF :Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII :C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII :C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, Ile581Thr, P = 5.10 × 10(-7) in EAs and P = 3.88 × 10(-3) in AAs) and VWF rs7962217 (Gly2705Arg,P = 6.30 × 10(-9) in EAs and P = 2.98 × 10(-2) in AAs. Significant associations for FVIII :C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P = 8.02 × 10(-10) ), with VWF rs1800380 in AAs (P = 5.62 × 10(-11) ), and with MAT1A rs2236568 in AAs (P51.69 × 10(-6) ). We replicated previously reported associations of FVIII :C and VWF :Ag with the ABO blood group, VWF rs1063856(Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII :C and VWF :Ag in both EAs and AAs.

Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.

OBJECTIVE: Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA. APPROACH AND RESULTS: Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0×10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9×10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3×10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0×10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0×10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke. CONCLUSIONS: We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.

The Israel Nationwide Heart Failure Survey: Sex differences in early and late mortality for hospitalized heart failure patients.

BACKGROUND: Current data on the influence of sex on the prognosis of heart failure (HF) are conflicting, possibly owing to the use of different end points and a heterogeneous heart failure population in earlier studies. We sought to evaluate the effect of sex on the risk of early and late mortality outcomes after hospitalization for acute heart failure. METHODS AND RESULTS: The prospective cohort study population comprised 2,212 hospitalized patients with acute HF enrolled in a multicenter national survey in Israel. Cox proportional-hazards regression modeling was used to evaluate the effect of sex on the risk of early (≤6 months) and late (>6 months to 4 years) mortality after the index hospitalization. Among the study patients, 998 (45%) were women. Women with HF displayed significantly different clinical characteristics compared with men, including older age, higher frequency of HF with preserved ejection fraction and hypertensive heart disease, and lower percentage of coronary artery disease (all P < .001). The fully adjusted multivariable analyses for mortality outcomes showed that women tended toward an increased risk for early (≤6 months) mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.96-1.41; P = .13), whereas men had significantly increased risk for late (>6 months) mortality (HR 1.25, 95% CI 1.09-1.43; P = .001). CONCLUSIONS: There are important differences in the clinical characteristics and the short- and long-term outcomes between men and women hospitalized with acute HF after adjusting for multiple confounding variables.

Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.

We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 × 10(-8)) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 × 10(-10)); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 × 10(-8)); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 × 10(-8)). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1.

Risk of acute myocardial infarction after the death of a significant person in one's life: the Determinants of Myocardial Infarction Onset Study.

BACKGROUND: Acute psychological stress is associated with an abrupt increase in the risk of cardiovascular events. Intense grief in the days after the death of a significant person may trigger the onset of acute myocardial infarction (MI), but this relationship has not been systematically studied. METHODS AND RESULTS: We conducted a case-crossover analysis of 1985 participants from the multicenter Determinants of Myocardial Infarction Onset Study interviewed during index hospitalization for an acute MI between 1989 and 1994. We compared the observed number of deaths in the days preceding MI symptom onset with its expected frequency based on each patient's control information, defined as the occurrence of deaths in the period from 1 to 6 months before infarction. Among the 1985 subjects, 270 (13.6%) experienced the loss of a significant person in the prior 6 months, including 19 within 1 day of their MI. The incidence rate of acute MI onset was elevated 21.1-fold (95% confidence interval, 13.1-34.1) within 24 hours of the death of a significant person and declined steadily on each subsequent day. The absolute risk of MI within 1 week of the death of a significant person is 1 excess MI per 1394 exposed individuals at low (5%) 10-year MI risk and 1 per 320 among individuals at high (20%) 10-year risk. CONCLUSIONS: Grief over the death of a significant person was associated with an acutely increased risk of MI in the subsequent days. The impact may be greatest among individuals at high cardiovascular risk.

Effects of omega-3 polyunsaturated fatty acids on platelet function in healthy subjects and subjects with cardiovascular disease.

Hyperactivation and aggregation of platelets play a major role in thrombosis and hemostasis. The aims of this study were to investigate the effects of omega-3 polyunsaturated fatty acids (PUFAs) on platelet function. Light transmission aggregometry and flow cytometric analyses of platelet activation and platelet-leukocyte aggregates were determined at baseline and after 4 weeks of omega-3 (docosahexaenoic acid 520 mg and eicosapentaenoic acid 120 mg) supplementation. In total, 40 healthy subjects and 16 patients with a history of cardiovascular disease (CVD) completed the study. In healthy subjects, omega-3 PUFA significantly reduced adenosine diphosphate (ADP)-induced (maximum amplitude, 77.0% ± 3.2% vs. 71.6% ± 3.4%, p = 0.036; maximum slope, 86.3 ± 1.8 vs. 80.7 ± 2.1, p = 0.014) and adrenaline-induced platelet aggregation (maximum slope, 42.8 ± 2.7 vs. 37.4 ± 3.0, p = 0.013; lag time, 00:21 ± 00:02 vs. 00:31 ± 00:03 s, p = 0.002). Omega-3 PUFA also reduced P-selectin expression (40.5% ± 2.9% vs. 34.4% ± 2.4%, p = 0.049) on platelets and platelet-monocyte aggregates (38.5% ± 2.6% vs. 31.4% ± 2.5%, p = 0.022) after activation with ADP 0.5 µM. There were fewer changes in platelet aggregation and activation found in subjects with CVD. Nevertheless, there was a reduction in the slope of arachidonic acid-induced platelet aggregation (13.21 ± 6.41 vs. 4.88 ± 3.01, p = 0.009) and increased lag time for U46619 (00:16 ± 00:00 vs. 00:29 ± 00:07 s, p = 0.018) induced platelet aggregation. Thus, 4-week supplementation of 640 mg omega-3 PUFA reduced measures of platelet aggregation and activation in healthy subjects but effects were less evident in patients with existing CVD. Our findings support the recommendation that the omega-3 PUFA dose be higher in CVD than among healthy subjects.

Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression.

Genetic variation is thought to contribute to variability in platelet function; however, the specific variants and mechanisms that contribute to altered platelet function are poorly defined. With the use of a combination of fine mapping and sequencing of the platelet endothelial aggregation receptor 1 (PEAR1) gene we identified a common variant (rs12041331) in intron 1 that accounts for ≤ 15% of total phenotypic variation in platelet function. Association findings were robust in 1241 persons of European ancestry (P = 2.22 × 10⁻8) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 × 10⁻²7) and in an independent sample of 2755 persons of European descent (P = 1.64 × 10⁻5). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 × 10⁻6) for the relation between the PEAR1 gene and platelet function phenotype. A dose-response relation between the number of G alleles at rs12041331 and expression of PEAR1 protein in human platelets was confirmed by Western blotting and ELISA. Similarly, the G allele was associated with greater protein expression in a luciferase reporter assay. These experiments identify the precise genetic variant in PEAR1 associated with altered platelet function and provide a plausible biologic mechanism to explain the association between variation in the PEAR1 gene and platelet function phenotype.

Screening, referral and treatment for depression in patients with coronary heart disease.

In 2003, the National Heart Foundation of Australia position statement on "stress" and heart disease found that depression was an important risk factor for coronary heart disease (CHD). This 2013 statement updates the evidence on depression (mild, moderate and severe) in patients with CHD, and provides guidance for health professionals on screening and treatment for depression in patients with CHD. The prevalence of depression is high in patients with CHD and it has a significant impact on the patient's quality of life and adherence to therapy, and an independent effect on prognosis. Rates of major depressive disorder of around 15% have been reported in patients after myocardial infarction or coronary artery bypass grafting. To provide the best possible care, it is important to recognise depression in patients with CHD. Routine screening for depression in all patients with CHD is indicated at first presentation, and again at the next follow-up appointment. A follow-up screen should occur 2-3 months after a CHD event. Screening should then be considered on a yearly basis, as for any other major risk factor for CHD. A simple tool for initial screening, such as the Patient Health Questionnaire-2 (PHQ-2) or the short-form Cardiac Depression Scale (CDS), can be incorporated into usual clinical practice with minimum interference, and may increase uptake of screening. Patients with positive screening results may need further evaluation. Appropriate treatment should be commenced, and the patient monitored. If screening is followed by comprehensive care, depression outcomes are likely to be improved. Patients with CHD and depression respond to cognitive behaviour therapy, collaborative care, exercise and some drug therapies in a similar way to the general population. However, tricyclic antidepressant drugs may worsen CHD outcomes and should be avoided. Coordination of care between health care providers is essential for optimal outcomes for patients. The benefits of treating depression include improved quality of life, improved adherence to other therapies and, potentially, improved CHD outcomes.

Psychosocial risk factors for coronary heart disease.

In 2003, the National Heart Foundation of Australia published a position statement on psychosocial risk factors and coronary heart disease (CHD). This consensus statement provides an updated review of the literature on psychosocial stressors, including chronic stressors (in particular, work stress), acute individual stressors and acute population stressors, to guide health professionals based on current evidence. It complements a separate updated statement on depression and CHD. Perceived chronic job strain and shift work are associated with a small absolute increased risk of developing CHD, but there is limited evidence regarding their effect on the prognosis of CHD. Evidence regarding a relationship between CHD and job (in)security, job satisfaction, working hours, effort-reward imbalance and job loss is inconclusive. Expert consensus is that workplace programs aimed at weight loss, exercise and other standard cardiovascular risk factors may have positive outcomes for these risk factors, but no evidence is available regarding the effect of such programs on the development of CHD. Social isolation after myocardial infarction (MI) is associated with an adverse prognosis. Expert consensus is that although measures to reduce social isolation are likely to produce positive psychosocial effects, it is unclear whether this would also improve CHD outcomes. Acute emotional stress may trigger MI or takotsubo ("stress") cardiomyopathy, but the absolute increase in transient risk from an individual stressor is low. Psychosocial stressors have an impact on CHD, but clinical significance and prevention require further study. Awareness of the potential for increased cardiovascular risk among populations exposed to natural disasters and other conditions of extreme stress may be useful for emergency services response planning. Wider public access to defibrillators should be available where large populations gather, such as sporting venues and airports, and as part of the response to natural and other disasters.