White Blood Cell Subtypes Are Associated with a Greater Long-Term Risk of Death after Acute Myocardial Infarction

We evaluated the association between white blood cell counts and long-term mortality rates in 2,129 patients (mean age, 65.3 ± 13.5 yr; 69% men) who had survived acute myocardial infarction. We obtained white blood cell counts and differential counts of white blood cell subtypes within the first 72 hours of hospital admission. The primary outcome was all-cause death at 1, 5, and 10 years after acute myocardial infarction. In regard to death in the long term, we found significant negative linear associations (lymphocytes), positive linear associations (neutrophils and the neutrophil-to-lymphocyte ratio), and nonlinear U-shaped associations (basophils, eosinophils, monocytes, and total white blood cell count). After multivariate adjustment for the Soroka Acute Myocardial Infarction risk score, lymphocytes (strongest association), neutrophil-to-lymphocyte ratio, and eosinophils were independently associated with death for up to 10 years after hospital discharge. The independent associations weakened over time. We conclude that lymphocyte count, neutrophil-to-lymphocyte ratio, and eosinophil count are independently and incrementally associated with death in the long term after acute myocardial infarction

Predictors of long-term (10-year) mortality postmyocardial infarction: Age-related differences. Soroka Acute Myocardial Infarction (SAMI) Project

AbstractBackgroundCardiovascular diseases are the leading cause of death in elderly people. Over the past decades medical advancements in the management of patients with acute myocardial infarction (AMI) led to improved survival and increased life expectancy. As short-term survival from AMI improves, more attention is being shifted toward understanding and improving long-term outcomes.AimTo evaluate age-associated variations in the long-term (up to 10 years) prognostic factors following AMI in “real world” patients, focusing on improving risk stratification of elderly patients.MethodsA retrospective analysis of 2763 consecutive AMI patients according to age groups: ≤65 years (n=1230) and >65 years (n=1533). Data were collected from the hospital's computerized systems. The primary outcome was 10-year postdischarge all-cause mortality.ResultsHigher rates of women, non-ST-elevation AMI, and most comorbidities were found in elderly patients, while the rates of invasive treatment were lower. During the follow-up period, mortality rate was higher among the older versus the younger group (69.7% versus 18.6%). Some of the parameters included in the interaction multivariate model had stronger association with the outcome in the younger group (hyponatremia, anemia, alcohol abuse or drug addiction, malignant neoplasm, renal disease, previous myocardial infarction, and invasive interventions) while others were stronger predictors in the elderly group (higher age, left main coronary artery or three-vessel disease, and neurological disorders). The c-statistic values of the multivariate models were 0.75 and 0.74 in the younger and the elder groups, respectively, and 0.86 for the interaction model.ConclusionsLong-term mortality following AMI in young as well as elderly patients can be predicted from simple, easily accessible clinical information. The associations of most predictors and mortality were stronger in younger patients. These predictors can be used for optimizing patient care aiming at mortality reduction

Psychological factors correlate meaningfully with percent-monocytes among acute coronary syndrome patients (in special issue on pschological risk factors and immune system involvement in cardiovascular disease)

Recent research demonstrates the importance of inflammatory parameters in the etiology and prognosis of the acute coronary syndrome (ACS). This study explored relations between psychological factors and immunological parameters routinely measured among ACS patients. Forty-two ACS patients completed questionnaires assessing perceived-control, emotional support, hostility, and life-events 2–4 days after hospitalization. Data on total leukocytes and percentages (%) of monocytes, %neutrophils, and %lymphocytes upon admission to hospital were collected from computerized medical charts as well as various biomedical information and risk-factors (e.g., diagnosis, left-ventricle—LV functioning, smoking, and hypertension). Of all significant biomedical variables, LV-function and arrival-time correlated uniquely with total leukocytes. Controlling for LV-function and arrival-time, hostility and life-events positively correlated with %monocytes, and perceived-control and emotional-support inversely correlated with %monocytes. Emotional-support was positively correlated and life-events were negatively correlated with %neutrophils. Macrophages play a pivotal role in plaque instability, the trigger of an ACS. This initiating role, and our finding of a relationship between recruitment of monocytes and a poor psychosocial profile, predictive of ACS, are consistent with a PNI component in the pathophysiology of ACS

Molecular and cellular interface between behavior and acute coronary syndromes

This review article integrates empirical findings from various scientific disciplines into a proposed psychoneuroimmunological (PNI) model of the acute coronary syndrome (ACS). Our starting point is an existing, mild, atherosclerotic plaque and a dysfunctional endothelium. The ACS is triggered by three stages. (1) Plaque instability: Pro-inflammatory cytokines (IL-1, IL-6, TNF-?) and chemoattractants (MCP-1, IL-8) induce leukocyte chemoattraction to the endothelium, and together with other triggers such as the CD40L–CD40 co-stimulation system activate plaque monocytes (macrophages). The macrophages then produce matrix metalloproteinases that disintegrate extra-cellular plaque matrix, causing coronary plaque instability. Acute stress, hostility, depression and vital exhaustion (VE) have been associated with elevated pro-inflammatory cytokines and leukocyte levels and their recruitment. (2) Extra-plaque factors promoting rupture: Neuro-endocrinological factors (norepinephrine) and cytokines induce vasoconstriction and elevated blood pressure (BP), both provoking a vulnerable plaque to rupture. Hostility/anger and acute stress can lead to vasoconstriction and elevated BP via catecholamines. (3) Superimposed thrombosis at a ruptured site: Increases in coagulation factors and reductions in anticoagulation factors (e.g. protein C) induced by inflammatory factors enhance platelet aggregation, a key stage in thrombosis. Hostility, depression and VE have been positively correlated with platelet aggregation. Thrombosis can lead to severe coronary occlusion, clinically manifested as an ACS. Thus, PNI processes might, at least in part, contribute to the pathogenesis of the ACS. This chain of events may endure due to lack of neuroendocrine-to-immune negative feedback stemming from cortisol resistance. This model has implications for the use of psychological interventions in ACS patients

A case series of concomitant treatment of perhexiline with amiodarone

Concomitant treatment with amiodarone and perhsexiline has been considered to be relatively contraindicated because of the hypothetical risk of potentiated adverse effects mediated by additive inhibition of carnitine palmitoyl transferase 1