Giuseppe Berton

C-reactive protein in acute myocardial infarction: association with heart failure

BACKGROUND High C-reactive protein (CRP) levels have been associated with higher mortality rate in patients with acute myocardial infarction (AMI). However, it is not known whether inflammation plays a role in the time-course of heart failure (HF) in this clinical setting. Our aim was to study the nature of the relationship between CRP and HF during AMI. METHODS This prospective study was carried out in 269 subjects admitted to the hospital for suspected AMI. Of these, 220 had evidence of AMI. The other 49 subjects were studied as controls. CRP was assessed on the first, third, and seventh day after admission. RESULTS CRP was significantly higher in the patients with AMI than in the control patients (P =.001) and peaked on the third day. Among the patients with AMI, CRP was higher in patients with HF than in patients without HF (adjusted P =.008, P =.02 and P =.03 on 1st, 3rd, and 7th day, respectively). Prevalence of HF on admission was slightly higher in the subjects with first-day CRP >or=15 mg/L than in those with CRP <15 mg/L, and the between-group difference progressively increased from the first to the seventh day (P <.0001). At multivariable regression analysis, first-day log-CRP was shown to be a strong independent predictor of both HF progression (P <.0001) and left ventricular ejection fraction (P <.0001). One-year total mortality and HF-mortality rates turned out to be higher in the patients with CRP >or=85 mg/L than in those with CRP below that level (P <.0001), and log-third-day CRP was independently associated with 1-year mortality at multivariable analysis (P =.0001). CONCLUSIONS CRP on admission to hospital is suitable for predicting the time-course of HF in patients with AMI. Peak CRP value is a strong independent predictor of global and HF-mortality during the following year.

Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: usefulness of a combined clinical and electrophysiologic approach

Aims Risk stratification in individuals with type 1 Brugada electrocardiogram (ECG) pattern (type 1 ECG) for primary prevention of sudden death (SD). Methods and results Three hundred and twenty patients (258 males, median age 43 years) with type 1 ECG were enrolled. No patient had previous cardiac arrest. Fifty-four per cent of patients had a spontaneous and 46% a drug-induced type 1 ECG. One-third had syncope, two-thirds were asymptomatic. Two hundred and forty-five patients underwent electrophysiologic study (EPS) and 110 patients received an implantable cardiac defibrillator (ICD). During follow-up [median length 40 months (IQ20-67)], 17 patients had major arrhythmic events (MAE) (14 resuscitated ventricular fibrillation (VF) and three SD). Both a spontaneous type 1 ECG and syncope significantly increased the risk (2.6 and 3.0% event rate per year vs. 0.4 and 0.8%). Major arrhythmic events occurred in 14% of subjects with positive EPS, in no subjects with negative EPS and in 5.3% of subjects without EPS. All MAE occurred in subjects who had at least two potential risk factors (syncope, family history of SD, and positive EPS). Among these patients, those with spontaneous type 1 ECG had a 30% event rate. Conclusion (1) In subjects with the Brugada type 1 ECG, no single clinical risk factor, nor EPS alone, is able to identify subjects at highest risk; (2) a multiparametric approach (including syncope, family history of SD, and positive EPS) helps to identify populations at highest risk; (3) subjects at highest risk are those with a spontaneous type 1 ECG and at least two risk factors; (4) the remainder are at low risk.

Albumin excretion rate increases during acute myocardial infarction and strongly predicts early mortality.

BACKGROUND This study was undertaken to assess whether albumin excretion rate (AER) increases during acute myocardial infarction (AMI) and whether it predicts in-hospital mortality. METHODS AND RESULTS The study was carried out in 496 subjects admitted to hospital for suspected AMI. Of these, 360 had evidence of AMI. The other 136 were studied as control subjects. AER was assessed by radioimmunoassay in three 24-hour urine collections performed on the first, third, and seventh days after admission. Left ventricular ejection fraction was measured by two-dimensional echocardiography in 254 subjects. AER adjusted for several confounders was higher in the AMI than the non-AMI group on the first (69.2+/-5.2 versus 27.3+/-8.5 mg/24 h, P<.0001) and third (30.3+/-2.7 versus 12.5+/-4.4 mg/24 h, P=.001) days, whereas no difference was present on the seventh day. When the subjects with heart failure were excluded, the difference between the two groups remained significant (first day, P<.0001; third day, P=.001). On the basis of classification of the 26 AMI patients who died in hospital according to whether they had normal AER, microalbuminuria, or overt albuminuria, mortality rate progressively increased with increasing levels of AER (P<.0001). In a Coxs proportional hazards model, AER was a better predictor of in-hospital mortality than Killip class or echocardiographic left ventricular ejection fraction. A cutoff value of 50 mg/24 h for first-day AER and 30 mg/24 h for third-day AER yielded a sensitivity of 92.3% and of 88.5% and a specificity of 72.4% and of 79.3%, respectively, for mortality. Adjusted relative risks for the two cutoff values were 17.3 (confidence limits, 4.6 to 112.7) and 8.4 (confidence limits, 2.4 to 39.3), respectively. CONCLUSIONS These data show that AER increases during AMI and that it yields prognostic information additional to that provided by clinical or echocardiographic evaluation of left ventricular performance.

Relationship between albumin excretion rate, ambulatory blood pressure and left ventricular hypertrophy in mild hypertension

Objective To study the relationship of urinary albumin excretion to ambulatory blood pressure and other cardiovascular risk factors in borderline to mild hypertension. Patients and methods We studied 779 patients with borderline to mild hypertension (mean±SEM age 33±0.3 years; mean±SEM office blood pressure 146±0.4/94±0.2 mmHg) at 17 hypertension clinics in northeast Italy. Office and 24-h blood pressures were recorded with simultaneous urine collection for albumin measurement. In 510 subjects, left ventricular mass was measured by echocardiography. Results Subjects with overt (>30 mg/24 h) and borderline (16–29 mg/24 h) microalbuminuria had similar 24-h blood pressure levels, higher than those in the subjects without microalbuminuria. In the univariate and multiple regression analyses the albumin excretion rate was closely correlated with 24-h systolic blood pressure and not related to age, body mass index, metabolic parameters, lifestyle factors and degree of left ventricular hypertrophy. Conclusions Borderline values of urinary albumin excretion (16–29 mg/24 h) may be clinically relevant in subjects with borderline to mild hypertension. Renal and cardiac damage do not develop in parallel in the initial phases of hypertension.

Effects of low altitude exposure on 24-hour blood pressure and adrenergic activity

Abstract The circulatory response to acute exposure to high altitude (>3,000 m) has been extensively studied.1–3 Sympathetic activation that occurs immediately after the exposure produces an abrupt increase in blood pressure (BP) and heart rate (HR), which persists for a few days.4,5 Subsequently, both BP and HR gradually return to normal levels. In contrast, the circulatory changes caused by exposure to a lower altitude (

Structural Abnormalities and Not Diastolic Dysfunction Are the Earliest Left Ventricular Changes in Hypertension

It has been claimed that diastolic dysfunction is the earliest cardiac abnormality in hypertension, preceding the development of left ventricular (LV) structural abnormalities. To detect early signs of hypertensive cardiac involvement 722 subjects (533 men and 189 women), 18-45 years old, with stage I hypertension, were studied by M-mode and Doppler echocardiography. Blood pressure was measured by 24-h ambulatory monitoring. Ninety-five normotensive individuals of similar age and gender distributions were studied as controls. Significant, though modest, changes of LV mass and geometry were found in the participants in comparison with the normotensive controls. The increment was +10.4 g/m2 for LV mass index, +1.8 mm for LV wall thickness, and +0.032 for relative wall thickness. A slight increase in atrial filling peak velocity was found in the hypertensive subjects at Doppler analysis of transmitral flow, but the ratio of early to atrial velocity of LV diastolic filling did not differ between the two groups. In multiple regression analyses, which included age, body mass index, heart rate, smoking, and physical activity, 24-h mean blood pressure emerged as a significant predictor of LV mass index (men, P = .003; women, P = .04) and wall thickness (men, P = .03; women, P = .004) in the hypertensive subjects, whereas no index of diastolic filling was significantly associated with ambulatory blood pressure in either gender. The present data indicate that changes in LV anatomy are the earliest signs of hypertensive cardiac involvement. Left ventricular filling is affected only marginally in the initial phase of hypertension.

Does long-lasting sports practice increase the risk of atrial fibrillation in healthy middle-aged men? Weak suggestions, no objective evidence.

Background Some authors have suggested that sports activity can increase the risk of atrial fibrillation in healthy middle-aged men. Therefore, sport activity, although it prevents coronary artery disease, might be the cause of a potentially dangerous arrhythmia. Methods To verify this assumption, we critically analyzed the current literature including original articles, reviews and meta-analyses. Results and conclusions All published articles showed several limitations. The data provided by published studies support the following conclusions: the incidence of atrial fibrillation in sporting middle-aged men is rare (<0.5% per year); a possible facilitating effect on atrial fibrillation is limited to vigorous endurance exercise, not to less vigorous sports; there are no convincing data to demonstrate that sport itself may be the cause of atrial fibrillation in healthy middle-aged men; and a facilitating effect of long-lasting sport cannot be excluded in middle-aged individuals with cardiovascular disorders. Nevertheless, the beneficial effects of exercise should offset this supposed risk, which, albeit increased, remains low.

Long-Term Effect of Continuing Sports Activity in Competitive Athletes With Frequent Ventricular Premature Complexes and Apparently Normal Heart

The long-term outcome of athletes with frequent ventricular premature complexes (VPCs) and apparently normal heart has not been fully clarified. To evaluate the clinical and prognostic significance of VPCs and the influence of continuing sports activity during follow-up, we studied 120 healthy athletes (96 men; median age 16 years) in whom frequent VPCs (>100 VPCs/24 hours) were discovered by chance during preparticipation screening. All athletes were followed up for a median of 84 months. During follow-up, 96 underwent serial 24-hour Holter recording and 62 underwent serial echocardiography. The median number of VPCs/24 hours on basal Holter was 3,760. During follow-up, 81 athletes continued sports activity, whereas 39 did not. No athlete died or developed overt heart disease. The median number of VPCs/24 hours decreased in both athletes who continued sports activity and those who did not (from 3,805 to 1,124, p <0.0001 and from 5,787 to 1,298, p <0.0001, respectively). During follow-up, left ventricular ejection fraction slightly decreased to <55% in 9 of 62 athletes who, in respect to the remaining 53, had more VPCs/24 hours both in the basal state (12,000 vs 3,880) and during follow-up (10,702 vs 1,368), and a longer follow-up (95 vs 36 months). In conclusion, (1) frequent VPCs in athletes without heart disease have a long-term benign prognostic significance, (2) sporting activity does not modify this benign outcome, (3) during follow-up, the burden of VPCs decreases whether or not subjects continue sports activity, and (4) in 14.5% of athletes, ejection fraction slightly decreases over time.

Albumin excretion in acute myocardial infarction: A guide for long-term prognosis

BACKGROUND Albumin excretion rate has been found to be associated with increased risk of mortality in several clinical settings. We assessed the relationship between urinary albumin and 7-year mortality in a cohort of patients with acute myocardial infarction (AMI). METHODS In this prospective study, we examined 505 white patients admitted with AMI to the intensive care unit of 3 hospitals. Main end points were nonearly all-cause and cardiovascular (CV) mortality. Albumin-to-creatinine ratio (ACR) was measured by radioimmunoassay on the first, third, and seventh days after admission. Risk estimates were made using Cox proportional-hazard model and relative odds. Forty patients (7.9%) died early inhospital, and 175 (34.7%) died during the rest of the follow-up (nonearly mortality). RESULTS The ACR measured on the third day predicted the occurrence of 7-year nonearly all-cause and CV mortality. Hazard ratios for ACR > or =0.97 mg/mmol were 3.0 (95% confidence limit 2.2-4.1), P < .0001, for nonearly all-cause mortality and 3.5 (95% confidence limit 2.5-5.0), P < .0001, for CV mortality. Correspondent fully adjusted hazard ratios were 1.9 (95% CI 1.4-2.6), P < .0001, and 2.2 (95% CI 1.5-3.2), P < .0001, respectively. By adding ACR to the 18-variable predictive model, ACR improved significantly both the goodness of fitting of the model for nonearly all-cause (P < .0001) and CV mortality (P < .0001) and the C-statistic value (P < .0001 and P = .002 for nonearly all-cause and CV mortality, respectively). Similar results were obtained for ACR measured on the first day or the seventh day. CONCLUSIONS An early increase of urinary albumin in AMI is a strong independent predictor of long-term adverse clinical outcome. The ACR improved clinical prediction over and above baseline traditional multivariable risk models.

Acute-phase inflammatory markers during myocardial infarction: association with mortality and modes of death after 7 years of follow-up.

Background The relationship between acute-phase inflammatory markers in the setting of acute myocardial infarction (AMI) and long-term outcomes is largely unexplored. Objectives The aim of the study was to investigate the predictive power of acute-phase inflammatory markers following AMI for short-term and long-term mortality separately and modes of death. Methods In 220 unselected patients with AMI [median age 67 (interquartile range 60–74) years, women 26%], blood neutrophil granulocytes, erythrocyte sedimentation rate, C-reactive protein, and α1-acid glycoprotein were measured 1, 3 and 7 days after admission. All patients completed 7 years of follow-up. Endpoints were 1-year (short-term) and 2- to 7-year (long-term) mortality and modes of death, classified as nonsudden cardiovascular, sudden, and noncardiovascular death. Results The short-term mortality rate was 18%. The long-term mortality rate was 26%. The short-term mortality risk was higher in patients in whom the markers were in the upper tertile. Fully adjusted hazard ratios (and 95% confidence interval) were 3.2 (1.4–7.9), 3.5 (1.7–7.9), 3.5 (1.6–8.6), and 6.1 (2.3–19.1) for neutrophil granulocyte, erythrocyte sedimentation rate, C-reactive protein, and α1-acid glycoprotein, respectively. The excess mortality was chiefly due to nonsudden cardiovascular mortality [fully adjusted hazard ratios were 4.6 (1.7–14.7), 4.7 (1.9–13.7), 5.9 (2.0–21.3) and 5.5 (2.0–17.6), respectively], whereas no association was found with sudden death or noncardiovascular modes of death. In the long term, the association with mortality and modes of death was no longer significant. Conclusion The acute-phase inflammatory markers tested following AMI are independently and concordantly associated with short-term mortality and their prediction is associated only with nonsudden cardiovascular modes of death. These markers are not associated with long-term mortality.