Low lymphocyte count and cardiovascular diseases.

Inflammation plays a crucial pathophysiological role in the entire continuum of the atherosclerotic process, from its initiation, progression, and plaque destabilization leading ultimately to an acute coronary event. Furthermore, once the clinical event has occurred, inflammation also influences the left ventricular remodelling process. Under the same paradigm, there is evidence that lymphocytes play an important role in the modulation of the inflammatory response at every level of the atherosclerotic process. Low lymphocyte count (LLC) is a common finding during the systemic inflammatory response, and clinical and animal studies suggest that LCC plays a putative role in accelerated atherosclerosis. For instance, there is recent evidence that LLC is associated with worse outcomes in patients with heart failure, chronic ischemic heart disease and acute coronary syndromes. Further indirect evidence supports the pathologic role of LLC related to the fact that 1) lymphopenia--due to a decreased count of lymphocyte T cells--normally occurs as a part of the human ageing process, and 2) increased incidence of cardiovascular events has been reported in conditions where lymphopenia is common, such as renal transplant recipients, human immunodeficiency virus infection, survivors of nuclear disasters and autoimmune diseases. The aim of the present article is to review: a) the pathophysiological mechanisms that have been proposed for the observed association between LLC and cardiovascular diseases (CVD), b) the available evidence regarding the diagnostic and prognostic role attributable to LLC in patients with CVD, and; c) the potential therapeutic implications of these findings.

Clustering of target organ damage increases mortality after acute coronary syndromes in patients with arterial hypertension.

The impact of target organ damage (TOD) clustering in hypertensive patients with established cardiovascular disease has not been clearly defined. Multicentre, observational and prospective study of 1054 consecutive patients with acute coronary syndromes (ACSs). The objective was describing the impact of TOD on first-year mortality. Ankle-brachial index (ABI), left ventricular hypertrophy and renal dysfunction were assessed during hospital stay. Hypertensive patients accounted for 80% of the cohort and had slightly higher mean age, higher prevalence of risk factors, previous cardiovascular disease and TOD. During follow-up, mean time 387.9 (7.2) days and median 382 (364.0-430.0) days, mortality rate tended to be higher in hypertensive patients (6.1 versus 3.5%; P=0.16). Cox regression survival analysis identified pathological ABI as the only TOD independently associated with mortality. When assessed globally, the presence of at least one TOD predicted mortality only in patients with hypertension and differences in mortality rate appeared very early in the follow-up. A linear increase in mortality rate was observed with the clustering of TOD: 2.0%, if no TOD was present, 7.6% in one TOD, 11.1% in two TODs and 20.0%, if three TODs were present. An increased risk in the combined end point of ischaemic events was observed in hypertensive patients without TOD (odds ratio (OR): 3.18; 95% confidence interval (CI): 1.31-7.70; P=0.01) and was still higher in patients with hypertension and TOD (OR: 4.61; 95% CI: 1.90-11.80; P<0.01). TOD predicts mortality and ischaemic events of hypertensive patients after ACS.

Discrimination and mental health in Ecuadorian immigrants in Spain.

BACKGROUND: The aim of this study was to examine the effects of ethnic discrimination on the mental health of Ecuadorian immigrants in Spain and to assess the roles of material and social resources. METHODS: Data were taken from the "Neighbourhood characteristics, immigration and mental health" survey conducted in 2006 in Spain. Psychological distress measured as "Possible Psychiatric Case" (PPC) was measured by the GHQ-28. A logistic regression was fitted to assess the association between PPC and discrimination. Interactions of discrimination with social and material resources were tested using product terms. RESULTS: Some 28% of the participants met our definition of PPC. About 20% of those who reported no discrimination were PPCs, rising to 30% of those who sometimes felt discriminated against and 41% of those who continually perceived discrimination. The OR for continuous discrimination was 12 (95% CI 3.5 to 40.3) among those with high financial strain, and 10 (2.4 to 41.7) when there was lack of economic support. Emotional support had an independent effect on PPC (OR 1.8, 95% CI 1.0 to 3.6, for those who reported having no friends). Social integration through a community group or association was positively related to the probability of being a PPC (OR 1.7, 95% CI 1.0 to 2.9). CONCLUSION: Ethnic discrimination is associated with psychological distress in these Ecuadorian immigrants in Spain. Discrimination effects may be exacerbated among those facing economic stress and those without economic support. These particularly vulnerable immigrants should be the subject of social and health interventions.

Prognostic and therapeutic implications of dipyridamole stress cardiovascular magnetic resonance on the basis of the ischaemic cascade.

OBJECTIVE: To determine the prognostic and therapeutic implications of stress perfusion cardiovascular magnetic resonance (CMR) on the basis of the ischaemic cascade. SETTING: Single centre study in a teaching hospital in Spain. PATIENTS: Dipyridamole stress CMR was performed on 601 patients with ischaemic chest pain and known or suspected coronary artery disease. On the basis of the ischaemic cascade, patients were categorised in C1 (no evidence of ischaemia, n = 354), C2 (isolated perfusion deficit at stress first-pass perfusion imaging, n = 181) and C3 (simultaneous perfusion deficit and inducible wall motion abnormalities, n = 66). CMR-related revascularisation (n = 102, 17%) was defined as the procedure prompted by the CMR results and carried out within the next three months. RESULTS: During a median follow-up of 553 days, 69 major adverse cardiac events (MACE), including 21 cardiac deaths, 14 non-fatal myocardial infarctions and 34 admissions for unstable angina with documented abnormal angiography were detected. In non-revascularised patients (n = 499), the MACE rate was 4% (14/340) in C1, 20% (26/128) in C2 and 39% (12/31) in C3 (adjusted p value = 0.004 vs C2 and <0.001 vs C1). CMR-related revascularisation had neutral effects in C2 (20% vs 19%, 1.1 (0.5 to 2.4), p = 0.7) but independently reduced the risk of MACE in C3 (39% vs 11%, 0.2 (0.1 to 0.7), p = 0.01). CONCLUSIONS: Dypiridamole stress CMR is able to stratify risk on the basis of the ischaemic cascade. A small group of patients with severe ischaemia-simultaneous perfusion deficit and inducible wall motion abnormalities-are at the highest risk and benefit most from MACE reduction due to revascularisation.

Prevalence and prognostic influence of peripheral arterial disease in patients >or=40 years old admitted into hospital following an acute coronary event.

OBJECTIVE: A significant proportion of patients with ischemic heart disease have associated peripheral arterial disease (PAD), but many are asymptomatic and this condition remains underdiagnosed. We aimed to study the prevalence of PAD in patients with an acute coronary syndrome (ACS) and to evaluate its influence in hospital clinical outcomes. METHODS: The PAMISCA register is a prospective, multicenter study involving patients >or=40 years old with ACS admitted to selected Spanish hospitals. All patients had their ankle-brachial index (ABI) measured between days 3 and 7 after the ischemic event. RESULTS: 1410 ACS patients (71.4% male) were included. PAD determined by ABI was documented in 561 patients (39.8%). Factors independently related to PAD were age (OR: 1.04; 95% CI: 1.03-1.06; p<0.001), smoking (OR: 1.88; 95% CI: 1.41-2.49; p<0.0001), diabetes (OR: 1.30; 95% CI: 1.02-1.65; p<0.05), previous cardiac disease (OR: 1.54; 95% CI: 1.22-1.95; p<0.001) and previous cerebrovascular disease (OR: 1.90; 95% CI: 1.28-2.80; p<0.001). Following the ACS, an ABIor=40 years presenting with ACS is high and it is associated with increased cardiovascular risk.

Prognostic value of leukocytosis in acute coronary syndromes: the cinderella of the inflammatory markers.

In recent years, numerous studies have validated the role of inflammation in the pathogenesis of atherosclerosis. Several of such studies have produced compelling evidence that inflammation participates in both, the initiation and perpetuation of the atherosclerotic process. Furthermore, epidemiological observations have found basal white blood cell (WBC) count is strongly associated with future cardiovascular disease (CVD), highlighting the participation of leukocytes in the pathogenesis of the ischemic damage that occurred during an acute coronary event, in particularly during the acute myocardial infarction (MI). Fundamentally, an acute MI triggers a systemic response to a necrotic insult characterized by leukocytosis and acute-phase protein synthesis. In this setting, elevated WBC count plays a central role in the reparative process that takes place to replace the necrotic tissue for collagen. In addition to be a proxy for the intensity of the peri-infarction inflammatory response, recent evidence has also shown that an elevated WBC counts, measured during the acute phase of MI, to be associated with adverse outcomes. This relationship holds true even when adjusting for classical prognostic variables some of which are surrogates for the extension of the infarcted-area. WBC count prognostic value in absence of necrosis marker elevation (like unstable angina), however, remains unclear and controversial. Additionally, and essentially due to its simplicity, cost-effectiveness and wide availability, WBC count has drawn the attention of researchers as a potential stratification tool in acute coronary syndromes (ACS). However, a formal comparison is needed between WBC count with other inflammatory markers such high-sensitive C-reactive protein to fully characterize its diagnostic accuracy.

[Glucose levels in non-diabetic patients. Is it a prognostic factor in acute coronary syndrome?]. / Niveles de glucemia en pacientes no diabéticos. 'Es un factor pronóstico en el síndrome coronario agudo?

INTRODUCTION: The role of glucose elevation above levels considered normal in non- diabetic patients with acute coronary syndromes (ACS) is not adequately defined. The aim of this study was to determine the association between serum glucose at admission and 1-year mortality in this type of patients. METHODS: We studied 648 non diabetic patients admitted consecutively with ACS. Serum glucose was determined at admission, together with classical risk factors, biochemical and inflammatory markers. The primary endpoint was all cause mortality at one year follow-up. RESULTS: Patients with normal glucose had lower mortality than patients with impaired fasting glucose (14.1% vs 5.7% 1-year mortality) or with glucose levels in diabetic range (24.7% vs 5.7% 1-year mortality). CONCLUSIONS: In non-ST elevation acute coronary syndromes, elevated levels of glucose in non-diabetic patients are strong predictors of all cause death at one year follow-up. This prognostic value is independent of other risk factors biochemical and inflammatory markers.

Microvascular perfusion 1 week and 6 months after myocardial infarction by first-pass perfusion cardiovascular magnetic resonance imaging.

OBJECTIVE: To characterise the evolution of myocardial perfusion during the first 6 months after myocardial infarction by first-pass perfusion cardiovascular magnetic resonance imaging (CMR) and determine its significance. DESIGN: Prospective cohort design. SETTING: Single-centre study in a teaching hospital in Spain. PATIENTS: 40 patients with a first ST-elevation myocardial infarction, single-vessel disease and thrombolysis in myocardial infarction (TIMI) grade 3 flow (stent in 33 patients) underwent rest and low-dose dobutamine CMR 7 (SD 1) and 184 (SD 11) days after infarction. Microvascular perfusion was assessed at rest by visual assessment and quantitative analysis of first-pass perfusion CMR. Of the 640 segments, 290 segments subtended by the infarct-related artery (IRA) were focused on. RESULTS: Both 1 week and 6 months after infarction, segments with normal perfusion showed more wall thickening, contractile reserve and wall thickness, and less transmural necrosis, p <0.05 in all cases. Of 76 hypoperfused segments at the first week, 47 (62%) normalised perfusion at the sixth month. However, 42 segments (14% of the whole group) showed chronic abnormal perfusion; these segments showed worse CMR indices in the late phase (p<0.05 in all cases). CONCLUSIONS: In patients with an open IRA, more than half of the segments with abnormal perfusion at the first week are normally perfused after six months. First-pass perfusion CMR shows that in a small percentage of segments, abnormal perfusion may become a chronic phenomenon-these areas have a more severe deterioration of systolic function, wall thickness, contractile reserve and the transmural extent of necrosis.

Risk stratification of patients with acute chest pain and normal troponin concentrations.

OBJECTIVE: To investigate the outcome of patients with acute chest pain and normal troponin concentrations. DESIGN: Prospective cohort design. SETTING: Single centre study in a teaching hospital in Spain. PATIENTS: 609 consecutive patients with chest pain evaluated in the emergency department by clinical history (risk factors and a chest pain score according to pain characteristics), ECG, and early (< 24 hours) exercise testing for low risk patients with physical capacity (n = 283, 46%). All had normal troponin concentrations after serial determination. MAIN OUTCOME MEASURES: Myocardial infarction or cardiac death during six months of follow up. RESULTS: 29 events were detected (4.8%). No patient with a negative early exercise test (n = 161) had events versus the 6.9% event rate in the remaining patients (p = 0.0001). Four independent predictors were found: chest pain score > or = 11 points (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1 to 5.5, p = 0.04), diabetes mellitus (OR 2.3, 95% CI 1.1 to 4.7, p = 0.03), previous coronary surgery (OR 3.1, 95% CI 1.3 to 7.6, p = 0.01), and ST segment depression (OR 2.8, 95% CI 1.3 to 6.3, p = 0.003). A risk score proved useful for patient stratification according to the presence of 0-1 (2.7% event rate), 2 (10.2%, p = 0.008), and 3-4 predictors (29.2%, p = 0.0001). CONCLUSIONS: A negative troponin result does not assure a good prognosis for patients coming to the emergency room with chest pain. Early exercise testing and clinical data should be carefully evaluated for risk stratification.

Valsalva sinus pseudoaneurysm causes acute myocardial infarction and stroke simultaneously.

Spontaneous Valsalva sinus pseudoaneurysm is a rare and highly lethal condition. Below we present a clinical case of a young woman with spontaneous Valsalva sinus pseudoaneurysm diagnosed presenting with acute myocardial infarction (AMI) and ischemic stroke.

Correlates of wellbeing of spousal and children carers of disabled people over 65 in Spain.

BACKGROUND: The aim of this study was to evaluate the associations between carer's wellbeing and stressors and to assess if these associations are different for spousal and children carers of disabled elderly. METHODS: Information was collected by home interviews of a population sample of carers (N = 195), who were providing assistance in activities of daily living to a community-dwelling population over 65. Associations between indicators of wellbeing (number of depressive symptoms, number of physical symptoms, self-perceived health and life satisfaction) and caring stressors were examined, controlling for carer's socio-economic characteristics and health status. Hierarchical logistic regressions were used to fit the data. Religion and social support were included as resources and spousal and children differential associations were tested. RESULTS: The four indicators of wellbeing are moderately correlated, indicating a common underlying concept. Spousal carers have lower socio-economic status, poorer health and lower levels of wellbeing than children carers. However, children carers bear a significantly greater burden. In the multivariate analysis of the associations between wellbeing and stressors, the similarities between spouse and adult child carers are more striking than the differences. Emotional support was consistently associated with higher levels of wellbeing while the associations of religiosity and instrumental support with wellbeing did not reach statistical significance. CONCLUSION: As formal care services are being developed in Spain, their ability to work in a supportive way with family networks should be taken into account. Research should be carried out on patterns of formal care interventions that use the resources in the natural support network of the family.

Sociodemographic characteristics and HIV risk behaviour patterns of male sex workers in Madrid, Spain.

This paper describes the sociodemographic and work characteristics, prevalence of HIV infection and associated risk behaviours among male sex workers (MSWs) in Madrid (Spain). Using an anonymous semi-structured questionnaire, educators attached to a mobile unit under a street-based prostitution programme surveyed 84 MSWs from several Madrid areas. Of the total surveyed: 35% were immigrants, mean age was 23 years, mean period in prostitution was four years; 21% had no primary education; 16% had injected drugs at some time; 11% reported private sexual relationships exclusively with women; 89% always used condoms in anal practices with clients; and 41% were in sexual relationships with their partners. Only 11% had ever used fortified condoms. In the preceding month, 37% had experienced condom failure, 82% without having used any lubricant. In all, 67% reported having undergone HIV testing, with a higher percentage of positive results among injecting (60%) versus non-injecting drug users (17%). Immigrants had a lower level of education, made less use of condoms, had more condom failures and, in their private lives, a greater proportion reported sexual relationships exclusively with women. In Spain, MSWs should be included in HIV prevention programmes, which ought to be specifically adapted to immigrants. Priority should be given to reducing the condom failure rate in anal intercourse, by improving access to fortified condoms.

QT dispersion within the first 6 months after an acute myocardial infarction: relationship with systolic function, left ventricular volumes, infarct related artery status and clinical outcome.

INTRODUCTION: We analysed QT dispersion within the first 6 months postinfarction, its relationship with the main established risk stratifiers and its clinical value. METHODS AND RESULTS: In 55 patients with a first Q-wave myocardial infarction the 12-lead electrocardiogram was scanned and digitised for analysis of QT dispersion (QT maximum-QT minimum) at first day (72 [61-96] ms), first week (69 [47-90] ms), first month (67 [46-88] ms) and sixth month (47 [40-74] ms; P<0.0001 vs. first day). Cardiac catheterization was performed at first week and at sixth month; QT dispersion was not related to ejection fraction, left ventricular volumes, infarct related artery status or contractile reserve (improvement of the infarcted area with low-dose dobutamine); no relation was found between QT dispersion decrease from first week to sixth month with regional systolic function improvement. Finally, during a mean follow-up period of 35+/-22 months QT dispersion was not independently related to clinical events. CONCLUSION: QT dispersion decreases progressively during the first months after myocardial infarction. These changes should be taken into account to define cut-off values of clinical interest in this phase. This variable does not seem related to the classic prognosis predictors. In a nonselected postinfarction population it has a low clinical value.

Salud e inmigración; a propósito del sida / Health and inmigration; talking about aids

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The effect of oral hormone replacement therapy on lipoprotein profile, resistance of LDL to oxidation and LDL particle size.

OBJECTIVES: To disclose if oral estradiol (E(2)), alone or in combination with natural progesterone (P) or medroxyprogesterone acetate (MPA), may modify the oxidizability of low density lipoprotein (LDL), and if the effect is achieved at physiological dosages. LDL oxidizability was assessed by the resistance to oxidation by copper and by the particle size profile, since small particles have increased oxidation susceptibility. METHODS: Thirty-three women received two consecutive, two-month length doses of 1 and 2 mg/day of oral E(2). They were then randomly assigned to a fourteen-day treatment of 2 mg/day E(2) plus either 300 mg/day P or 5 mg/day MPA. A parallel group of experiments was performed on a pool of baseline plasma, where hormones were added at the desired concentration. Lipoprotein levels, resistance of LDL to oxidation, and LDL particle diameter, were measured at baseline and after each treatment. RESULTS: Estradiol reduced LDL levels and increased high density lipoprotein (HDL) and triglycerides. P abolished these changes, whereas MPA only reversed the increase of HDL. Estradiol protected LDL from oxidation in a dose-dependent manner, although only at pharmacological concentrations (1 microM or higher). Both P and MPA were inert at either physiological or pharmacological concentrations. The size of the LDL particles remained unaffected except under MPA, in which it was reduced. CONCLUSIONS: Estradiol has a protective effect against LDL oxidation, although only at pharmacological dosages. P and MPA did not limit the E(2) action. The size of the LDL particles remained unaltered after each E(2) dose, but MPA, and not P, was associated with a diminution.

Relationships between heart rate variability, functional capacity, and left ventricular function following myocardial infarction: an evaluation after one week and six months.

BACKGROUND: Relationships between heart rate (HR) variability and different prognostic markers such as ejection fraction, functional capacity, and patency of the infarct-related artery, as well as the comparison of their time courses are not fully elucidated. HYPOTHESIS: The aim of study was to assess prospectively the early postinfarction changes in HR variability and its evolution over a period of 6 months: the relationships between HR variability and functional capacity in exercise testing; left ventricular function in cardiac catheterization: status of the infarct-related artery; and the comparison of their time courses. METHODS: In 42 patients with anterior myocardial infarction, a study was made of the early changes in HR variability analyzed by the complex demodulation method, its evolution over a period of 6 months. and the relationships between HR variability and (1) functional capacity in exercise testing, (2) left ventricular function in cardiac catheterization, and (3) status of the infarct-related artery. RESULTS: At 1 week HR variability parameters correlated directly with functional capacity indicators such as METS, percent change in HR from rest to peak exercise (%deltaHR), difference between initial and peak HR (HR range), percent peak theoretical HR (% peak HR), left ventricular ejection fraction (EF), and, inversely, with end-systolic volume (ESV). Stepwise multiple regression analysis to establish HR variability parameters (recorded at 1 week) as related to functional capacity and left ventricular function at 1 week and 6 months postinfarction established the following variables: (1) At 1 week: standard deviation (SD) of the RR cycles in relation to %deltaHR (r = 0.60, p <0.0001), HR range (r = 0.43, p < 0.01), and EF (r = 0.79, p < 0.0001). (2) At 6 months, the sole accepted HR variability parameter was the SD in relation to %deltaHR (r = 0.38, p < 0.05) and HR range (r = 0.45, p < 0.01). No variability parameter was accepted in relation to METS, % peak HR, or ESV. Relationship between EF or ESV and HR variability parameters was not significant when both were evaluated at 6 months. At that time, there was a significant increase in all HR variability parameters among all surviving patients (n = 39), with the exception of the LF/HF ratio and mean RR cycle. The percent increase in HR variability between the first week and 6 months was greater among those patients with the lowest basal EF. No relation was established between HR variability and patency of the infarct-related artery. CONCLUSION: The decrease in HR variability observed following myocardial infarction is associated with a diminished functional capacity and an increased alteration of the EF. This does not affect the recovery of HR variability, which was observed in all surviving patients.