Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. METHODS: ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. RESULTS: The intake of ω-3 below the median (< 1.7 g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p = 0.004], Interleukin-2 [OR:2.46(1.20-5.04); p = 0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p = 0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p = 0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p = 0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. CONCLUSION: These findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling. TRIAL REGISTRATION: Clinical Trial Registry number and website: NCT02062554 .

Validation of surrogate indexes of insulin sensitivity in acute phase of myocardial infarction based on euglycemic-hyperinsulinemic clamp.

The decrease in insulin sensitivity (IS) during myocardial infarction (MI) is recognized as a possible contributor to poor patient outcomes. Despite its potential relevance, a standardized and convenient IS assessment tool has yet to be established for said clinical scenarios. This study aimed to validate the accuracy of surrogate indexes in determining IS in acute MI patients by comparison with the gold standard reference method for measuring IS, the euglycemic-hyperinsulinemic clamp (EHC). We performed EHCs in 31 consecutive nondiabetic patients who were admitted within the first 24 h of symptoms of ST-segment elevation MI. Patients with prior diagnosis of diabetes, use of hypoglycemic agents, or a glycosylated hemoglobin ≥6.5% were excluded. EHCs were performed at the second day (D2) and sixth day (D6) post-MI. Basal (12-h fasting) blood samples from D2 and D6 were used to evaluate patient blood glucose and insulin levels. We then calculated the following surrogate indexes: homeostatic model assessment of insulin sensitivity (HOMA2S), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). The IS index measured by EHC (ISiclamp) was correlated to HOMA2S, HOMA-IR, and QUICKI at D2 (r = 0.485, P = 0.009; r = -0.384, P = 0.048; r = 0.479, P = 0.01, respectively) and D6 (r = 0.621, P = 0.002; r = -0.576, P = 0.006; r = 0.626, P = 0.002, respectively). Receiver operator characteristic curves made for discrimination of ISiclamp above the median in D2 and D6 depicted areas under the curve of 0.740, 0.734, and 0.760 for HOMA2S, HOMA-IR, and QUICKI, respectively. Bland-Altman plots displayed no apparent systematic error for indexes, but a propensity for proportional error, particularly with HOMA-IR. Thus, based on EHC, these simple surrogate indexes are feasible for assessing IS during MI.

Timing and dose of statin therapy define its impact on inflammatory and endothelial responses during myocardial infarction.

OBJECTIVE: Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. METHODS AND RESULTS: ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (P<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P=0.001). CONCLUSIONS: This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00906451.

Statin Use in the Early Phase of ST-Segment Elevation Myocardial Infarction Is Associated With Decreased QTc Dispersion.

BACKGROUND: Although there is strong evidence supporting the use of statin therapy after myocardial infarction (MI), some mechanistic gaps exist regarding the benefits of this therapy at the very onset of MI. Among the potential beneficial mechanisms, statins may improve myocardial electrical stability and reduce life-threatening ventricular arrhythmia, as reported in stable clinical conditions. This study was designed to evaluate whether this mechanism could also occur during the acute phase of MI. METHODS: Consecutive patients with ST-segment elevation MI were treated without statin (n = 57) or with a simvastatin dose of 20 to 80 mg (n = 87) within the first 24 hours after MI symptom onset. Patients underwent digital electrocardiography within the first 24 hours and at the third and fifth days after MI. The QTC dispersion (QTcD) was measured both with and without the U waves. RESULTS: Although QTcD values were equivalent between the groups at the first day (80.6 ± 36.0 vs 80.0 ± 32.1; P = 0.36), they were shorter among individuals using simvastatin than in those receiving no statins on the third (90.4 ± 38.6 vs 86.5 ± 36.9; P = .036) and fifth days (73.1 ± 31 vs 69.2 ± 32.6; P = .049). We obtained similar results when analyzing the QTcD duration including the U wave. All values were adjusted by an ANCOVA model after propensity-score matching. CONCLUSIONS: Statins administered within 24 hours of ST-segment elevation MI reduced QTc dispersion, which may potentially attenuate the substrate for life-threatening ventricular arrhythmias.

Adverse interaction between HDL and the mass of myocardial infarction.

BACKGROUND AND AIMS: Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ. METHODS: HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (n = 94) and peak CKMB (n = 393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers. RESULTS: HDL-C above the median (35 mg/dL) was associated with higher peak CKMB [255 (145-415) vs. 136 (84-287) UI/L; p = 0.02], higher MI mass [17 (9-21) vs. 10 (6-14) g; p < 0.01] and lower left ventricular ejection fraction [47 (34-53) vs. 51 (43-59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p < 0.01) and MI mass (p < 0.01) only in reperfused patients with time to reperfusion <4 h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p < 0.01) and improved dP/dt max (p = 0.02). CONCLUSIONS: In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.

Statin Short-term Inhibition of Insulin Sensitivity and Secretion During Acute Phase of ST-Elevation Myocardial Infarction.

Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by -6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and -2% ± 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.

Endothelial nitric oxide synthase genotypes modulate peripheral vasodilatory properties after myocardial infarction.

BACKGROUND: Studies in population genetics suggest an important relationship between the eNOS G894T polymorphism and occurrence of acute myocardial infarction (AMI), with little known on its influence on the post-AMI period. AIM: To investigate the association of allelic variants produced by the G894T transversion in eNOS (rs1799983) with post-AMI variables. METHODS: Cross-sectional analyses of anthropometric, clinical and laboratory assessments obtained within the first 24h and after 5 and 30 days of the AMI event across T carriers and G homozygotes of eNOS in 371 consecutive cases of AMI with ST-segment elevation admitted to a Brazilian emergency service in cardiology. Genotypes were determined by polymerase chain reaction followed by enzymatic restriction. RESULTS: Despite no difference between genotypic groups on aspects as Killip-Kimbal classification scores, extension of infarcted mass, lipid profile or pattern of medication use, an increase in serum nitric oxide from admission to day 5 was higher for T carriers (p<0.001). Thirty days post-AMI, peripheral blood flow reserve was larger among T carriers either by flow- (p=0.037) and nitrate-mediated (p=0.040) dilation testing. CONCLUSION: Our results suggest an association of the eNOS 894T allele with an apparent improvement in late arterial function in post-AMI patients.

Coronary artery calcification score is an independent predictor of the no-reflow phenomenon after reperfusion therapy in acute myocardial infarction.

AIM/BACKGROUND: Abundant evidence shows that coronary artery calcification (CAC) is a strong marker of structural and functional changes within the artery wall. Thus far, the implications of CAC in patients with acute coronary syndromes remain unclear. We aimed to investigate whether the CAC score is associated with impaired reperfusion during the acute phase of ST-elevation myocardial infarction (STEMI). METHODS: We enrolled 60 consecutive STEMI patients to undergo cardiac computed tomography for assessment of the CAC score within 1 week after STEMI. Coronary thrombus burden, coronary blood flow (TIMI flow), and myocardial blush grade (MBG) were evaluated systematically. Patients with maximal TIMI flow and MBG were grouped as optimal reperfusion (n=27) and their counterparts as no-reflow (NR, n=33). RESULTS: There were no differences in the clinical characteristics between groups. Patients in the NR group had higher heart rate, coronary angiographic severity, and CAC score. CAC score greater than 100 was associated independently with the presence of NR (odds ratio 4.4, 95% confidence interval 1.17-16.3). The CAC score of nonculprit coronary arteries was higher in NR individuals than in their counterparts (P=0.04). In addition, the CAC score of the isnfarct-related artery correlated negatively with the TIMI-flow rate (r=-0.54, P<0.001) and with the MBG (r=-0.32, P=0.04). CONCLUSION: The CAC score is associated with the presence of the NR phenomenon in STEMI patients.

Glycosylated hemoglobin is associated with decreased endothelial function, high inflammatory response, and adverse clinical outcome in non-diabetic STEMI patients.

OBJECTIVE: Chronic dysglycemia was recently identified as a predictor for adverse outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. Data for non-diabetic patients who underwent thrombolysis is scarce. In this context, we aimed to study the effect of HbA1c on cardiovascular outcome after STEMI. METHODS: A prospective cohort of 326 non-diabetic STEMI individuals was used for the analyses. We measured plasma glucose, hemoglobin A1c [HbA1c], lipid profile, C-reactive protein (CRP), and nitrate/nitrite (NOx) upon admission and five days after STEMI (D5). Flow-mediated dilation (FMD) was performed 30 days after STEMI. During clinical follow-up, we assessed patients for incident diabetes (progression to HbA1c ≥ 6.5%) and major adverse cardiac events (MACE), defined as a composite of fatal and non-fatal MI, sudden cardiac death, and angina requiring hospitalization. RESULTS: Using ROC-curve analysis, a 5.8% HbA1c best predicted MACE with a sensitivity of 75% and specificity of 53% (AUC 0.673, p = 0.001). Patients were categorized as high HbA1c if ≥ 5.8% and low HbA1c if <5.8%. Compared with patients with low HbA1c, those with high HbA1c presented with 20% higher CRP-D5 (p = 0.009) and 19% higher ΔCRP (p = 0.01), a 32% decrease in ΔNOx (p < 0.001), and 33% lower FMD (p < 0.001). After a median follow-up of 1.9 (1.1-2.8) years, patients with high HbA1c had more incident diabetes (HR 2.3 95% CI 1.01-5.2; p = 0.048) and MACE (HR 3.32 95% CI 1.09-10.03; p = 0.03). CONCLUSION: Non-diabetic STEMI patients with high HbA1c present with decreased endothelial function and increased inflammatory response and long-term risk of MACE.

HDL levels and oxidizability during myocardial infarction are associated with reduced endothelial-mediated vasodilation and nitric oxide bioavailability.

OBJECTIVE: Acute phase response modifies high-density lipoprotein (HDL) into a dysfunctional particle that may favor oxidative/inflammatory stress and eNOS dysfunction. The present study investigated the impact of this phenomenon on patients presenting ST-elevation myocardial infarction (STEMI). METHODS: Plasma was obtained from 180 consecutive patients within the first 24-h of onset of STEMI symptoms (D1) and after 5 days (D5). Nitrate/nitrite (NOx) and lipoproteins were isolated by gradient ultracentrifugation. The oxidizability of low-density lipoprotein incubated with HDL (HDLaoxLDL) and the HDL self-oxidizability (HDLautox) were measured after CuSO4 co-incubation. Anti-inflammatory activity of HDL was estimated by VCAM-1 secretion by human umbilical vein endothelial cells after incubation with TNF-α. Flow-mediated dilation (FMD) was assessed at the 30(th) day (D30) after STEMI. RESULTS: Among patients in the first tertile of admission HDL-Cholesterol (<33 mg/dL), the increment of NOx from D1 to D5 [6.7(2; 13) vs. 3.2(-3; 10) vs. 3.5(-3; 12); p = 0.001] and the FMD adjusted for multiple covariates [8.4(5; 11) vs 6.1(3; 10) vs. 5.2(3; 10); p = 0.001] were higher than in those in the second (33-42 mg/dL) or third (>42 mg/dL) tertiles, respectively. From D1 to D5, there was a decrease in HDL size (-6.3 ± 0.3%; p < 0.001) and particle number (-22.0 ± 0.6%; p < 0.001) as well as an increase in both HDLaoxLDL (33%(23); p < 0.001) and HDLautox (65%(25); p < 0.001). VCAM-1 secretion after TNF-a stimulation was reduced after co-incubation with HDL from healthy volunteers (-24%(33); p = 0.009), from MI patients at D1 (-23%(37); p = 0.015) and at D30 (-22%(24); p = 0.042) but not at D5 (p = 0.28). CONCLUSION: During STEMI, high HDL-cholesterol is associated with a greater decline in endothelial function. In parallel, structural and functional changes in HDL occur reducing its anti-inflammatory and anti-oxidant properties.

Peri-infarct zone characterized by cardiac magnetic resonance imaging is directly associated with the inflammatory activity during acute phase myocardial infarction.

Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55 ± 10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p = 0.02), IL-2 (3.6 vs. 3.4 times; p = 0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p = 0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r = 0.69), delta-CRP (r = 0.7), IL-2-D5 (r = 0.5), delta-IL-2 (r = 0.6), TNF-α (r = 0.5), delta-TNF-α (r = 0.4; p = 0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.

Elevated CETP activity during acute phase of myocardial infarction is independently associated with endothelial dysfunction and adverse clinical outcome.

OBJECTIVE: Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). METHODS: Consecutive patients with STEMI (n = 116) were enrolled <24-h of symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFα), 8-isoprostane, nitric oxide (NOx) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography. RESULTS: Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFα, 8-isoprostane levels or CTB. The rise in NOx from D1 to D5 was inferior [3.5(-1; 10) vs. 5.5(-1; 12); p < 0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p = 0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thiobarbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r = 0.72; p = 0.014) and FMD (r = -0.61; p = 0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25-132; p = 0.032) and 180 days (OR 3.3; 95% CI 1.03-10.7; p = 0.044). CONCLUSIONS: An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome.

High-density lipoprotein levels are strongly associated with the recovery rate of insulin sensitivity during the acute phase of myocardial infarction: a study by euglycemic hyperinsulinemic clamp.

BACKGROUND: The decrease of insulin sensitivity (IS) during myocardial infarction (MI) is strongly associated with increased morbidity and mortality. Recent data suggest that in individuals under stable conditions, high-density lipoprotein (HDL) may improve IS. To date, the role of HDL in the modulation of IS in acute metabolic stress conditions such as MI remains unknown. OBJECTIVE: To explore the association between plasma HDL-C and the change in IS during the acute phase of MI. METHODS: Consecutive nondiabetic patients with ST-segment elevation MI (n = 22) underwent direct measurement of IS through the euglycemic hyperinsulinemic clamp on the first morning and on the fifth day after onset of MI. Patients were grouped according to HDL-C levels at admission above and below the median value (35 mg/dL). RESULTS: At admission, there was no significant difference in baseline IS index, clinical, anthropometric, or treatment characteristics between low and high HDL groups. Between admission and fifth day, there was a decrease of 8% in IS index in the low HDL group and an 11% increase in the high HDL group (P = .001 for intragroup and P = .012 for intergroup difference). This difference remained significant after we controlled for the sex, age, waist circumference, triglycerides, baseline IS index, and statin dose during hospitalization. CONCLUSION: This is the first study to provide evidence that plasma levels of HDL-C are strongly associated with the recovery rate of IS during the acute phase of MI.

Diabetes mellitus unawareness is a strong determinant of mortality in patients manifesting myocardial infarction.

OBJECTIVE: Often, as diabetes mellitus type 2 (T2DM) evolves insidiously, prevention is commenced late and diagnosis is made when vascular damage has been set. Hence, our hypothesis is that T2DM awareness may influence the outcome of atherothrombotic events. METHODS: A consecutive cohort of patients manifesting ST-elevation myocardial infarction (MI) was classified according to the presence and awareness of the diagnosis of T2DM: known diabetes (kT2DM, n = 72), unknown diabetes (uT2DM, n = 80) and no diabetes (ND, n = 333). Medical history, laboratory data, and angiographic findings including myocardial blush grade (MBG) were prospectively obtained. The primary endpoint was in-hospital death and secondary endpoint was major adverse cardiac events (MACE) defined as sudden cardiac death, fatal MI and nonfatal MI that occurred from 30 days of study entry onwards. RESULTS: With the exception of glycated hemoglobin (p = 0.001) and triglycerides (p = 0.04), no differences were found between groups for all other biochemical, clinical or angiographic admission characteristics. Myocardial tissue reperfusion defined as MBG 3 was observed in 62% in the ND group, 50% in the kT2DM group and 23% in the uT2DM group (p = 0.01). All-cause in-hospital mortality was higher in uT2DM (16.7%) than in kT2DM (8.4%) and both groups had a higher mortality rate as compared with the ND group (3.8%, p = 0.01). During follow-up (653 ± 26 days), the incidence of MACE was higher in uT2DM than in kT2DM and in both compared to the ND group (p = 0.002). CONCLUSION: Unawareness of T2DM diagnosis is strongly associated with a poor short- and long-term outcome after MI.

High plasma HDL-C attenuates stress hyperglycemia during acute phase of myocardial infarction.

OBJECTIVE: During myocardial infarction (MI), a transient decrease of both insulin sensitivity and secretion triggers stress hyperglycemia, which is followed by a substantial increase in mortality. Recent findings in cellular models indicate that HDL may act on glucose homeostasis by improving insulin sensitivity and secretion. In this study, we explored this potential effect in patients during the acute phase of MI. METHODS: Plasma glucose, insulin and C-peptide were measured at admission in the first 24h and on the fifth day after MI with ST-segment elevation in 183 consecutive non-diabetic patients. Patients were divided into HDL-C quartiles for the analyses (Q1: <31, Q2: 31-38, Q3: 38-47 and Q4: >47mg/dL). The Homeostasis Model Assessment version 2 was used to assess insulin sensitivity (HOMA2S) and beta-cell function (HOMA2B). RESULTS: On admission, no difference was found between the quartiles in glucose (p=0.6), insulin (p=0.6) or C-peptide (p=0.5) levels, HOMA2S (p=0.9) or HOMA2B (p=1.0). On the fifth day there was a reduction in glucose levels whose intensity was directly proportional to the HDL-C quartile (p<0.001). At the same time, there was a reduction in plasma insulin (p<0.001) and C-peptides (p<0.001) whose magnitude was inversely proportional to the HDL-C quartile. Consistently, the increase of HOMA2S (p<0.001) and HOMA2B (p=0.01) were also positively associated with HDL-C levels. Furthermore, plasma HDL-C levels were inversely and independently associated with blood glucose change during the acute phase. CONCLUSION: This study demonstrates the association between low plasma HDL-C levels and increased duration of stress hyperglycemia during MI and suggests in humans the interaction between HDL and insulin secretion and sensitivity.

High sodium intake adversely affects oxidative-inflammatory response, cardiac remodelling and mortality after myocardial infarction.

OBJECTIVE: Enhanced sodium intake increases volume overload, oxidative stress and production of proinflammatory cytokines. In animal models, increased sodium intake favours ventricular dysfunction after myocardial infarction (MI). The aim of this study was to investigate, in human subjects presenting with ST-segment elevation MI (STEMI), the impact of sodium intake prior the coronary event. METHODS: Consecutive patients (n=372) admitted within the first 24 h of STEMI were classified by a food intake questionnaire as having a chronic daily intake of sodium higher (HS) or lower (LS) than 1.2 g in the last 90 days before MI. Plasma levels of 8-isoprostane, interleucin-2 (IL-2), tumour necrosis factor type α (TNF-α), C-reactive protein (CRP) and brain natriuretic peptide (BNP) were measured at admission and at the fifth day. Magnetic resonance imaging was performed immediately after discharge. Total mortality and recurrence of acute coronary events were investigated over 4 years of follow-up. RESULTS: The decrease of 8-isoprostane was more prominent and the increase of IL-2, TNF-α and CRP less intense during the first 5 days in LS than in HS patients (p<0.05). Sodium intake correlated with change in plasma BNP between admission and fifth day (r=0.46; p<0.0001). End-diastolic volumes of left atrium and left ventricle were greater in HS than in LS patients (p<0.05). In the first 30 days after MI and up to 4 years afterwards, total mortality was higher in HS than in LS patients (p<0.05). CONCLUSION: Excessive sodium intake increases oxidative stress, inflammatory response, myocardial stretching and dilatation, and short and long-term mortality after STEMI.

Most of the patients presenting myocardial infarction would not be eligible for intensive lipid-lowering based on clinical algorithms or plasma C-reactive protein.

OBJECTIVE: The study we assessed how often patients who are manifesting a myocardial infarction (MI) would not be considered candidates for intensive lipid-lowering therapy based on the current guidelines. METHODS: In 355 consecutive patients manifesting ST elevation MI (STEMI), admission plasma C-reactive protein (CRP) was measured and Framingham risk score (FRS), PROCAM risk score, Reynolds risk score, ASSIGN risk score, QRISK, and SCORE algorithms were applied. Cardiac computed tomography and carotid ultrasound were performed to assess the coronary artery calcium score (CAC), carotid intima-media thickness (cIMT) and the presence of carotid plaques. RESULTS: Less than 50% of STEMI patients would be identified as having high risk before the event by any of these algorithms. With the exception of FRS (9%), all other algorithms would assign low risk to about half of the enrolled patients. Plasma CRP was <1.0mg/L in 70% and >2mg/L in 14% of the patients. The average cIMT was 0.8±0.2mm and only in 24% of patients was ≥1.0mm. Carotid plaques were found in 74% of patients. CAC ≥100 was found in 66% of patients. Adding CAC ≥100 plus the presence of carotid plaque, a high-risk condition would be identified in 100% of the patients using any of the above mentioned algorithms. CONCLUSION: More than half of patients manifesting STEMI would not be considered as candidates for intensive preventive therapy by the current clinical algorithms. The addition of anatomical parameters such as CAC and the presence of carotid plaques can substantially reduce the CVD risk underestimation.

Effect of beta blockers (metoprolol or propranolol) on effect of simvastatin in lowering C-reactive protein in acute myocardial infarction.

Recent data indicated that statin therapy may fail to reduce the incidence of coronary events in patients concomitantly using beta blockers. The aim of the present study was to examine whether the concomitant use of beta blockers would modify the anti-inflammatory action of statins. Changes in C-reactive protein (CRP) between days 1 and 5 after myocardial infarction were evaluated in 189 patients treated with simvastatin alone (S), beta blockers alone (B; propranolol or metoprolol), S + B, or neither of these 2 medications (N) in a prospective observational cohort. At baseline, median CRP was lower in the S group (0.40 mg/dl, interquartile range 0.1 to 0.6) than the other groups (B: 0.6 mg/dl, interquartile range 0.4 to 1.6; S + B: 0.5 mg/dl, interquartile range 0.3 to 1.2; and N: 0.6 mg/dl, interquartile range 0.2 to 1.5). By day 5, median CRP was 1.3 mg/dl (interquartile range 0.7 to 2.6), 4.3 (interquartile range 1.6 to 8.8), 4.6 (interquartile range 2.8 to 9.5), and 4.4 (interquartile range 1.9 to 9.9) for the S, B, S + B, and N groups, respectively. After adjusting for log(e) baseline CRP, the difference in log(e) CRP between days 1 and 5 was significantly lower in the S group compared with the B (-0.74 +/- 0.23 [SE], p = 0.001) or S + B group (-0.99 +/- 0.20 [SE], p <0.0001). The significance remained after adjustment for age, gender, and baseline CRP. There was no significant difference in change in CRP between the SB and B groups. In conclusion, the present study confirmed the anti-inflammatory action of statins and showed that concomitant use of beta blockers may significantly attenuate this effect.

Rebound inflammatory response during the acute phase of myocardial infarction after simvastatin withdrawal.

OBJECTIVE: The present study aimed to verify the existence of a rebound inflammatory effect after statin withdrawal in the acute phase of myocardial infarction (MI). METHODS: In a prospective observational cohort, changes in C-reactive protein (CRP) between the first and the fifth day after MI were evaluated in 249 consecutive patients who were using statins prior to and during MI (SS), statins prior to but not during MI (SN), no statin prior to but during MI (NS), and no statin prior to nor during MI (NN). Data are presented as median (interquartile range). RESULTS: At baseline, statin users presented a trend to lower CRP values as compared with those without this treatment before the MI (NN: 1.0(0.4-1.5)mg/dL vs. NS: 1.0(0.3-2.8)mg/dL vs. SS: 0.5(0.3-1.0)mg/dL vs. SN: 0.6(0.4-1.0)mg/dL; p=0.08). By the fifth day, median CRP was significantly higher in the SN (18.1(16.1-23.2)mg/dL) group as compared with other groups (NN: 10.5(9.3-13.2)mg/dL vs. NS: 2.9(1.5-4.5)mg/dL vs. SS: 1.1(0.8-2.4)mg/dL; p<0.0001). At the fifth day, the median CRP in the NN group was lower than in the SN group (p<0.0001), but higher than the NS and SS groups (p<0.0001). There was no significant correlation between CRP change and the change of LDL-cholesterol, HDL-cholesterol or triglycerides. CONCLUSION: The present study has, for the first time, provided evidence for the existence of a rebound inflammatory effect after statin cessation. This rebound reaction may contribute for the adverse outcome of patients who stop statin treatment during MI.