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Background: Scientific research on atrial fibrosis in atrial fibrillation (AF) has mainly focused on quantitative or molecular features. The purpose of this study was to perform a clinicoarchitectural/structural investigation of fibrosis to provide one key to understanding the electrophysiological/clinical aspects of AF. Methods: We characterized the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting persistent AF (group 1; 59 males; 60±11 years; 91 mitral disease–related AF, 30 nonmitral disease–related AF) and from 39 patients in sinus rhythm with mitral valve regurgitation (group 2; 32 males; 59±12 years). Ten autopsy hearts served as controls. Results: Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which we arbitrarily subdivided into 4 stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and at a more advanced stage in group 1 versus group 2 and, within group 1, in patients with rheumatic disease versus nonrheumatic cases. In patients with AF with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69–150 cells/mm 2 , depending on the areas in AF biopsies). A few fibrocytes—circulating and bone marrow-derived mesenchymal cells—were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. Conclusions: Atrial fibrosis is an evolving and inhomogeneous histological/architectural change that progresses through different stages ranging from isolated foci to confluent sclerotic zones which—seemingly—constrain impulse conduction across restricted regions of electrotonically coupled cardiomyocytes. The fibrotic areas mainly consist of type I collagen extracellular matrix and, only to a lesser extent, mesenchymal cells.

Inherited cardiac diseases inducing structural remodeling of the myocardium sometimes develop arrhythmias of various kinds. Among these rhythm disturbances, atrial fibrillation is well known to frequently worsen the prognosis of the primary disorder by increasing morbidity and mortality, especially because of a higher rate of heart failure. In this manuscript, we have reviewed the literature on the most important inherited structural cardiac diseases in whose clinical history atrial fibrillation may occur fairly often.

The inadequate long-term efficacy of anti-arrhythmic therapy has been one of the main reasons for the development of non-pharmacological interventions for patients with atrial fibrillation such as catheter and surgical ablation. This has greatly increased interest in the functional morphology and electrophysiological properties of the atria and related anatomical structures. This article is the second of a two-part review that aims to provide anatomical and functional details concerning some of the principal anatomical sites commonly targeted by ablative procedures for treating atrial fibrillation, and covers pulmonary veins, ganglionated plexi, caval veins, and the ligament of Marshall. It also provides some general information about site-specific ablation procedures.

Minimally invasive atrial fibrillation surgery (MIAFS) has become a well established and increasingly used option for managing patients with stand-alone arrhythmia. Pulmonary veins (PVs) isolation continues to be the cornerstone of ablation strategies. Indeed, in most cases, atrial fibrillation (AF) is triggered in or near the PVs. Nevertheless, ectopic beats initiating AF may occasionally arise from non-PV foci. The knowledge of the anatomy and underlying morphology of PVs and non-PV foci is essential for cardiac surgeons treating AF patients with epicardial minimally invasive procedures. The anatomical structures relevant to the pathogenesis and the epicardial treatment of AF include the PVs, the pericardial space, the pericardial sinuses, the phrenic nerve, the left atrium, the retro-atrial and caval ganglionated plexuses, the ligament of Marshall, the caval veins and the left atrial appendage. In this review, we briefly describe the basic anatomy of these structures and discuss their specific correlations for cardiac surgeons interested in performing MIAFS.

Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in Winfree's “pinwheel experiment,” usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet ventricular arrhythmia vulnerability during normal sinus rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart. New features included single premature stimulation during normal sinus rhythm, stimulation and unipolar potential mapping from the same high-resolution epicardial electrode array, and progressive increase in stimulation strength and prematurity from diastolic threshold until arrhythmia induction. Measurements were performed with 1-ms cathodal stimuli at multiple test sites ( n = 26) in seven rats. Stimulus-induced virtual electrode polarization during sinus beat recovery phase influenced premature ventricular responses. Specifically, gradual increase in stimulus strength and prematurity progressively induced make, break, and graded-response stimulation mechanisms. Hence unidirectional conduction block occurred as follows: 1) along fiber direction, on right and left ventricular free walls ( n = 23), initiating figure-eight reentry ( n = 17) and tachycardia ( n = 12), and 2) across fiber direction, on lower interventricular septum ( n = 3), initiating spiral wave reentry ( n = 2) and tachycardia ( n = 1). Critical time window (55.1 ± 4.7 ms, 68.2 ± 6.0 ms) and stimulus strength lower limit (4.9 ± 0.6 mA) defined vulnerability to reentry. A novel finding of this study was that ventricular tachycardia evolves and is maintained by episodes of scroll-like wave and focal activation couplets. We also found that single low-intensity premature stimuli can induce repetitive ventricular response ( n = 13) characterized by focal activations. NEW & NOTEWORTHY We performed ventricular cathodal point stimulation during sinus rhythm by progressively increasing stimulus strength and prematurity. Virtual electrode polarization and recovery gradient progressively induced make, break, and graded-response stimulation mechanisms. Unidirectional conduction block occurred along or across fiber direction, initiating figure-eight or spiral wave reentry, respectively, and tachycardia sustained by scroll wave and focal activations.

In humans, depression is often triggered by prolonged exposure to psychosocial stressors and is often associated with cardiovascular comorbidity. Mounting evidence suggests a role for endocannabinoid signaling in the regulation of both emotional behavior and cardiovascular function. Here, we examined cardiac activity in a rodent model of social stress-induced depression and investigated whether pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid anandamide, exerts antidepressant-like and cardioprotective effects. Male Wistar Kyoto rats were exposed to five weeks of repeated social stress or control procedure. Starting from the third week, they received daily administration of the selective FAAH inhibitor URB694 (0.1 mg/kg, i.p.) or vehicle. Cardiac electrical activity was recorded by radiotelemetry. Repeated social stress triggered biological and behavioral changes that mirror symptoms of human depression, such as (i) reductions in body weight gain and sucrose solution preference, (ii) hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and (iii) increased immobility in the forced swim test. Moreover, stressed rats showed (i) alterations in heart rate daily rhythm and cardiac autonomic neural regulation, (ii) a larger incidence of spontaneous arrhythmias, and (iii) signs of cardiac hypertrophy. Daily treatment with URB694 (i) increased central and peripheral anandamide levels, (ii) corrected stress-induced alterations of biological and behavioral parameters, and (iii) protected the heart against the adverse effects of social stress. Repeated social stress in Wistar Kyoto rats reproduces aspects of human depression/cardiovascular comorbidity. Pharmacological enhancement of anandamide signaling might be a promising strategy for the treatment of these comorbid conditions.

Aims To describe atrial fibrillation (AF) management in member countries of the European Society of Cardiology (ESC) and to verify cardiology practices against guidelines. Methods and results Among 182 hospitals in 35 countries, 5333 ambulant and hospitalized AF patients were enrolled, in 2003 and 2004. AF was primary or secondary diagnosis, and was confirmed on ECG in the preceding 12 months. Clinical type of AF was reported to be first detected in 978, paroxysmal in 1517, persistent in 1167, and permanent in 1547 patients. Concomitant diseases were present in 90% of all patients, causing risk factors for stroke to be also highly prevalent (86%). As many as 69% of patients were symptomatic at the time of the survey; among asymptomatic patients, 54% were previously experienced symptoms. Oral anticoagulation was prescribed in 67 and 49% of eligible and ineligible patients, respectively. A rhythm control strategy was applied in 67% of currently symptomatic patients and in 44% of patients who never experienced symptoms. Conclusion This survey provides a unique snapshot of current AF management in ESC member countries. Discordance between guidelines and practice was found regarding several issues on stroke prevention and antiarrhythmic therapy.

Ablation of the left atrial free wall around the pulmonary vein ostia (LAFW) may be effective in the treatment of chronic atrial fibrillation associated with mitral disease (CAF-MVD). Using light and conventional electron microscopy analyses, we wanted to evaluate, in CAF-MVD, the interstitial remodeling in the LAFW as well as in a more remote region, such as the left atrial appendage (LAA). LAFW and LAA samples were obtained from 33 CAF-MVD patients during combined mitral surgery and radiofrequency ablation and from 16 autoptic controls. Interstitial fibrosis (IF) and perivascular fibrosis (PF), capillary densities and the maximal oxygen diffusion distance were morphometrically determined. In CAF-MVD patients, the LAFW, compared with the LAA, showed a higher percentage of IF (7.16+/-3.23% versus 2.51+/-1.40%, respectively), a lower myocardial capillary density per mm(2) (830+/-106 versus 989+/-173) and an increased oxygen maximal diffusion distance (19.70+/-1.27 microm versus 18.13+/-1.58 microm). All these values were also significantly different than controls. No differences were found in evaluating PF. At variance with the LAA, in CAF-MVD patients, the LAFW around the pulmonary vein ostia is a region characterized by a marked interstitial remodeling such that it may be morphologically indicated as an appropriate target for ablation treatment aimed at sinus rhythm restoration.

Acute myocardial infarction follows a circadian pattern, with a morning peak ascribed to sympathetic activation. However, about 20% of myocardial infarctions occur between midnight and 6 AM; these events may have different characteristics.We studied 1571 patients with acute myocardial infarction (866 anterior and 705 inferior myocardial infarctions) who were admitted to our coronary care units from January 1997 to February 2001. We noted the time of the infarction, its anatomic location, and the involved coronary arteries.Inferior myocardial infarctions were more frequent during the night (midnight to 6 AM) than during other periods of the day (n = 238, 34% of all inferior infarctions, P0.01). When coronary angiography was performed (795 patients), 92% (127/138) of inferior infarctions were due to right coronary artery occlusion, whereas only 54% (130/242) of the remaining inferior infarctions involved that artery.Inferior myocardial infarctions occur disproportionately at night, usually due to right coronary artery occlusion. This suggests that a protective role for sleep may be limited to left coronary artery-related events.

Cardiovascular disease increases with age as well as alterations of cardiac electrophysiological properties, but a detailed knowledge about changes in cardiac electrophysiology relevant to arrhythmogenesis in the elderly is relatively lacking. The aim of this study was to determine specific age-related changes in electrophysiological properties of the ventricles which can be related to a structural-functional arrhythmogenic substrate. Multiple epicardial electrograms were recorded on the ventricular surface of in vivo control and aged rats, while arrhythmia vulnerability was investigated by premature stimulation protocols. Single or multiple ectopic beats and sustained ventricular arrhythmias were frequently induced in aged but not in control hearts. Abnormal ventricular activation patterns during sinus rhythm and unchanged conduction velocity during point stimulation in aged hearts suggest the occurrence of impaired impulse conduction through the distal Purkinje system that might create a potential reentry substrate.

Previously, we observed that a single low-intensity premature ventricular stimulation could occasionally induce spontaneous ectopic beats in normal rat hearts. Possible hypothesis for the arrhythmia is that a premature beat can encounter a zone of conduction block to initiate reentry. However, enhanced dispersion of repolarization, a necessary condition for initiation of reentry, is unlikely to be present in normal myocardium. Thus, the main objective of the present study was to perform detailed pace mapping measurements in normal ventricular myocardium with a view to identify pacing sites and critical coupling intervals which could induce spontaneous ectopic beats and to characterize the reentrant circuits.

BACKGROUND The extent to which atrial myocardium is remodeled in patients with persistent lone atrial fibrillation (LAF) is largely unknown. OBJECTIVE The purpose of this study was to perform a clinicopathologic investigation in patients with persistent LAF. METHODS We characterized structural and molecular remodeling in atrial biopsies from 19 patients (17 males, mean age 49 years) with persistent (> 7 days; n = 8) or long-lasting persistent (> 1 year; n = 11) LAF who underwent surgical ablation. Atrial tissue from 15 autopsy samples without clinicopathologic evidence of heart disease served as controls. RESULTS Morphometric analysis showed cardiomyocyte hypertrophy and greater amounts of myolytic damage and interstitial fibrosis in persistent LAF patients compared to controls (P

Structural Remodeling in Atrial Fibrillation. Introduction: Atrial fibrillation (AF) in mitral regurgitation (MR) is a complex disease where multiple factors may induce left-atrial structural remodeling (SR). We explored the differential SR of the left-atrial posterior wall (LAPW) of patients affected by MR with or without persistent AF, and the expression of key proteins involved in its pathogenesis. Methods and Results: Light microscopy of LAPW samples from 27 patients with MR and persistent AF (group 1), 33 with MR in sinus rhythm (group 2), and 15 autopsy controls (group 3) was used to measure myocyte diameter, percentage of myocytolytic myocytes, interstitial fibrosis, and capillary density; RT-PCR and Western blotting were used to assess the mRNA and protein levels of SOD-1, SOD-2, HO-1, calpain, MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF; immunofluorescence was used to locate these proteins. Myocyte diameter was similar in groups 1 and 2, but larger than controls. Compared to group 2, group 1 had more myocytolytic myocytes (20.8 +/- 5.6% vs 14.7 +/- 4.5%; P < 0.0001), increased interstitial fibrosis (10.4 +/- 5.1% vs 7.5 +/- 4.2%; P < 0.05), and decreased capillary density (923 +/- 107 No/mm(2) vs 1,040 +/- 100 No/mm(2); P < 0.0001). All of the proteins were more expressed in groups 1 and 2 than in controls. The protein and mRNA levels of SOD-1, SOD-2, MMP-2, and MMP-9 were higher in group 1 than in group 2. Conclusions: The LAPW of MR patients with or without AF shows considerable SR. The former has more severe histopathological changes and higher levels of proteins involved in SR, thereby reaching a threshold beyond which the sinus impulse cannot normally activate atrial myocardium. (J Cardiovasc Electrophysiol, Vol. 23, pp. 271-279, March 2012)

Functional Anatomy of the Atria. The fact that some atrial and ventricular disorders (e.g., atrial fibrillation and heart failure) have a structural basis and cause atrial myocardial remodeling has led to increasing attention being paid to the atrial chambers. Furthermore, the rapid development of mapping and ablative procedures as a means of diagnosing and treating supraventricular arrhythmias has generated considerable interest in atrial gross anatomy, histology and ultrastructure. The aim of this article is to provide a comprehensive overview of the structure of the left and right atria (at macroscopic, histological and ultrastructural level) in relation to their function. In addition to analyzing normal atria, we also discuss functional anatomy in the case of atrial fibrillation and heart failure. (J Cardiovasc Electrophysiol, Vol. 22, pp. 223-235, February 2011)

A 2-month-old girl with poor appetite and failure to thrive was admitted because of pallor, dyspnea, and tachycardia with periodic gallop rhythm. Chest x-ray (Figure 1) showed cardiomegaly, and echocardiography (Figure 2) revealed left ventricular dilation (diastolic diameter, 41.5 mm [normal

A 47-year-old man with a history of gynecomastia due to prolactin-releasing pituitary microadenoma was admitted to the hospital because of persistent chest pain and fatigue. Chest x-ray showed pronounced enlargement of the cardiac profile (Figure 1), and echocardiography demonstrated a marked pericardial effusion (Figure 2). Pericardiocentesis allowed the drainage of 1800 mL of pericardial fluid whose biochemical analysis was consistent with an exudate (total protein and lactate dehydrogenase fluid-to-serum ratios of 0.9 and 2.6, respectively); cytological examination showed the presence of mesothelial cells, histiocytes, and lymphocytes. Figure 1. Chest x-ray performed at the time of admission to hospital showing marked enlargement of the cardiac profile. Figure 2. Transthoracic echocardiographic image, obtained on admission to hospital, …

Atrial fibrillation occurs and maintains itself in the context of a morphologically and functionally altered atrial substrate that can be induced by stressors such as underlying diseases (cardiac or noncardiac) or aging. The resultant structural remodeling is a slow process that progressively affects myocytes and the myocardial interstitium, and takes place from as early as the first days of atrial tachyarrhythmia. The left atrium, and particularly its posterior wall, is the location where remodeling is concentrated to the greatest extent. The mechanisms that underlie the remodeling process in atrial fibrillation have not yet been completely elucidated, although experimental and clinical investigations have indicated a number of signaling systems, inflammation, oxidative stress, atrial stretching and ischemia as factors involved in the cascade of events that leads to atrial fibrillation. The aim of this Review is to provide a comprehensive overview of the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and the established and hypothetical pathogenetic mechanisms involved in structural remodeling. This article also highlights the emerging therapies being developed to prevent progression of atrial fibrillation.

Atrial fibrillation becomes a self-perpetuating arrhythmia as a consequence of electrophysiologic and structural remodeling involving the atrium. Oxidative stress may be a link between this rhythm disturbance and electrophysiologic remodeling. The aim of this study was to evaluate whether the heme oxygenase-1 (HO-1) marker of oxidative stress was more expressed in left atrial sites with stronger structural remodeling in patients affected by chronic atrial fibrillation (CAF) and mitral valve disease (MD). Myocardial samples were taken from the left atrial posterior wall (LAPW) and left atrial appendage (LAA) of 24 patients with CAF-MD in addition to 10 autopsy controls. The levels of HO-1 messenger RNA (mRNA) and HO-1 protein in each pathologic LAPW and LAA were quantified using reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Furthermore, light microscopy was used to morphometrically evaluate the differential myocyte and interstitial changes in the same CAF-MD LAPW and LAA samples. In controls, HO-1 protein was quantified using enzyme-linked immunosorbent assay. Unlike controls, patients with CAF-MD had higher levels of HO-1 mRNA and its protein product, expressed as LAPW/LAA ratios, in the LAPW (2.18 +/- 1.18, P.0001, and 1.55 +/- 0.67, P.005), and their LAPW also showed greater histologic changes in myocytolytic myocytes (15.1% +/- 3.1% versus 6.9% +/- 3.3%, P.0001), interstitial fibrosis (8.2% +/- 2.2% versus 2.8% +/- 1.2%, P.0001), and capillary density (816 +/- 120 number/mm(2) versus 1114 +/- 188 number/mm(2); P.05). In addition, markers of oxidative stress were immunohistochemically studied with antinitrotyrosine and anti-iNOS antibodies. In patients with CAF-MD, the inducible enzyme HO-1 is more expressed in the left atrial areas that show greater structural remodeling. This finding strongly suggests a pathogenetic relationship between oxidative stress and the degree of histologic change.

It has been found that the pulmonary veins and adjacent left atrial posterior wall (LAPW) are deeply involved in both the initiation and maintenance of atrial fibrillation (AF), and the identification of these high-risk sites has aroused great interest in investigating their histopathologic substrate. We used light and conventional electron microscopy to evaluate the differential myocyte and interstitial changes in LAPW and left atrial appendage (LAA) samples from 28 patients with chronic AF undergoing mitral valve surgery and from 12 autoptic controls. There were always more myocytes with loss of sarcomeres in the LAPW than in the LAA (19.9% +/- 7.7% versus 8.2% +/- 5.0%; P < .0001), and the LAPW showed more marked immunohistochemical evidence of dedifferentiation, characterized by the reexpression of smooth muscle actin. In pathological left atria, myocyte diameter in the LAPW and LAA was comparable (19.0 +/- 1.5 versus 18.5 +/- 2.0 microm; not significant) but larger than in the controls (11.9 +/- 0.8 and 12.1 +/- 1.3 microm, respectively; P < .0001). A terminal deoxynucleotidyltransferase assay did not reveal any myocyte apoptosis. The LAPW also showed more interstitial fibrosis than the LAA (7.49% +/- 3.34% versus 2.80% +/- 1.35%; P < .0001). Ultrastructural examination confirmed the presence of myocyte myocytolysis in the perinuclear area and showed changes in mitochondrial shape. In conclusion, the LAPW in patients with chronic AF related to mitral valve disease seems to be a particular anatomical site in which major myocyte and interstitial changes are concentrated, whereas the LAA is more protected. This remodeling may increase the heterogeneity of LAPW electrical conduction, thus confirming this location as an elective target for the ablation treatment of AF.

The purpose of the present study was to evaluate the extent of the ventricular epicardial fat and its relationship with the underlying myocardium, neither of which is still completely understood.A total of 117 autoptic human hearts was subdivided into four groups: normals (N), ischemics (I), hypertrophics (H) and hypertrophic-ischemics (HI). In each heart, the ventricular myocardial and epicardial fat weights were measured. On the basis of these data, the epicardial fat percentage within the ventricles was calculated.The left, right and total ventricular fat weights were greater in H and HI than in N and I (P.05, P.05, P.01, respectively). No differences were detected in the epicardial fat weights in comparing H versus HI and N versus I. Moreover, the fat percentage in each ventricle did not vary between the four groups. However, if compared with the right ventricle, the left ventricle showed an epicardial fat percentage consistently lower (P.0001). In nonhypertrophied hearts (N and I), the body mass index and the total epicardial fat weight were correlated (P.05), whereas in hypertrophied hearts (H and HI), they were not.A constant fat-muscle ratio exists in each ventricle, which is not influenced by ischemia or hypertrophy. Accordingly, during the hypertrophic process, the ventricular fat and the underlying myocardium show a parallel and correlated increase in their masses.

In humans, chronic stressors have long been linked to cardiac morbidity. Altered serotonergic neurotransmission may represent a crucial pathophysiological mechanism mediating stress-induced cardiac disturbances. Here, we evaluated the physiological role of serotonin (5-HT) 1A receptors in the autonomic regulation of cardiac function under acute and chronic stress conditions, using 5-HT(1A) receptor knockout mice (KOs). When exposed to acute stressors, KO mice displayed a higher tachycardic stress response and a larger reduction of vagal modulation of heart rate than wild type counterparts (WTs). During a protocol of chronic psychosocial stress, 6 out of 22 (27%) KOs died from cardiac arrest. Close to death, they displayed a severe bradycardia, a lengthening of cardiac interval (P wave, PQ and QRS) duration, a notched QRS complex and a profound hypothermia. In the same period, the remaining knockouts exhibited higher values of heart rate than WTs during both light and dark phases of the diurnal rhythm. At sacrifice, KO mice showed a larger expression of cardiac muscarinic receptors (M2), whereas they did not differ for gross cardiac anatomy and the amount of myocardial fibrosis compared to WTs. This study demonstrates that chronic genetic loss of 5-HT(1A) receptors is detrimental for cardiovascular health, by intensifying acute, stress-induced heart rate rises and increasing the susceptibility to sudden cardiac death in mice undergoing chronic stress.

Background Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses are implicated in the pathogenesis of atherosclerosis and a premature AMI of parents is associated with an increased risk of the disease in their offspring (Offs). However, the genetic background of familiarity for AMI is still largely unknown. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. Results This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. In fact, the above genetic markers were more frequent in unaffected Offs (46.4%) and patients with sporadic AMI (31.8%) than in the CTR (17.3%) and the differences were highly statistically significant (Offs vs CTR: p = 0.0001, OR = 4.129; AMI vs CTR: p = 0.0001, OR = 2.224). During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. Conclusion Our data suggest that selected genes with immune regulatory functions are part of the complex genetic background contributing to familiarity for cardiovascular diseases. This inflammatory genetic profile, along with classical cardiovascular risk factors, may be used for better defining individual risk of AMI in unaffected subjects.