Characteristics and Long-Term Prognosis of Patients ≤35 Years of Age with ST Segment Elevation Myocardial Infarction and "Normal or Near Normal" Coronary Arteries.

There are scarce data regarding risk factors and prognosis of patients with premature ST segment elevation myocardial infarction (STEMI) and "normal or near normal" coronary arteries (N/NNCAs). We compared the characteristics and long-term prognosis of patients with premature STEMI and N/NNCAs with their counterparts with significant coronary artery disease (CAD). We recruited 330 patients who had STEMI ≤35 years of age and 167 age- and gender-matched controls. All patients underwent coronary angiography. Coronary arteries with no lesions or lesions causing <30% reduction in lumen diameter were defined as N/NNCAs, whereas narrowings causing ≥50% diameter reduction formed the significant CAD group. Lipid profile, homocysteine levels, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism were determined. Sixty patients (18%) had N/NNCAs. Patients with N/NNCAs had lower low-density lipoprotein-cholesterol and higher high-density lipoprotein-cholesterol levels, higher homocysteine levels, and higher prevalence of MTHFR TT genotype (34.6 vs 18%, p = 0.008) compared with patients with significant CAD. After a median follow-up of 8 years, cardiovascular events occurred in 105 (36%) of 291 patients with available follow-up data. Significant CAD was associated with higher risk for recurrent cardiovascular events after adjustment for traditional risk factors (hazard ratio 2.095, 95% confidence interval 1.088 to 3.664, p = 0.022) and additional adjustment for the left ventricular ejection fraction, reperfusion therapy, and persistent smoking (hazard ratio 1.869, 95% confidence interval 1.007 to 3.468, p = 0.041). In conclusion, patients with premature STEMI and N/NNCAs have fewer lipid abnormalities, higher homocysteine levels and prevalence of MTHFR TT genotype, and better long-term prognosis compared with their counterparts with significant CAD.

Circadian pattern of symptoms onset in patients ≤35 years presenting with ST-segment elevation acute myocardial infarction.

BACKGROUND: There are scarce data regarding the circadian pattern of symptoms onset in young patients presenting with acute myocardial infarction (AMI). We explored whether young patients with ST-segment elevation AMI exhibit a circadian variation in symptoms onset. METHODS: We recruited prospectively 256 consecutive patients who had survived their first ST-segment elevation AMI ≤35 years of age. Patients were categorized into 4 groups by 6-h intervals over 24 h. RESULTS: In 49 patients (19.1%) the clinical presentation of AMI was atypical. The symptoms onset was as follows: 00:01 to 06:00, 19.1%, 06:01 to 12:00, 32.4%; 12:01 to 18:00, 28.1%; and 18:01 to 24:00, 20.3%. There was a significant association between the time of day and the likelihood of symptoms onset (Rayleigh test, p<0.001). Between 00:01 and 06:00 the incidence of AMI onset was lower than expected and between 06:01 and 12:00 was higher (p=0.034 and p=0.011, respectively), whereas in the other 6-h period groups no difference was found between expected and observed AMI incidence (p=0.280 and p=0.131). No significant differences were found regarding clinical characteristics, i.e. traditional risk factors, reperfusion treatment of AMI, ejection fraction of left ventricle, time interval from pain onset to hospital arrival, dietary habits and physical activity, among the 6-h period groups. CONCLUSIONS: ST-segment elevation AMI in individuals ≤35 years of age follows a circadian pattern with a morning peak. This information might be useful for the prompt diagnosis and treatment of AMI in very young patients which occurs rarely and frequently with atypical clinical presentation.

Inflammatory markers and plaque morphology: an optical coherence tomography study.

BACKGROUND: OCT with its unique image resolution is the ideal method to detect culprit lesion characteristics in different clinical presentations. The identification of inflammatory markers related to plaque characteristics may be of clinical importance. METHODS: Thirty-two patients with acute coronary syndromes (ACS) and fourteen patients with stable angina pectoris (SAP) were enrolled in this study. Culprit lesion morphology was assessed by optical coherence tomography (OCT) in patients with ACS and SAP. The possible relations between serum levels of high sensitivity-C reactive protein (hs-CRP) and interleukin-18 (IL-18) with plaque characteristics were investigated in those patients. RESULTS: Plaque rupture and thin-cap fibroatheroma (TCFA) were detected more frequently in ACS patients compared with SAP patients, (78.6% vs. 14.3%, p<0.001, 92.9% vs. 14.3%, p<0.001, respectively). Higher levels of serum hs-CRP and IL-18 were found in patients with plaque rupture vs. those with no plaque rupture (median value: 19.2mg/L vs. 1.6 mg/L, p<0.001 and 219.5 pg/ml vs. 127.5 pg/ml, p=0.001 respectively), and TCFA vs. those without TCFA (median value: 15.2mg/L vs. 1.6 mg/L, p=0.004 and 209.0 pg/ml vs.153.2 pg/ml, p=0.03 respectively). Serum hs-CRP was the only independent predictor of plaque rupture (p=0.02, odds ratio 1.1, 95% confidence interval 1.0 to 1.2). A cut-off value of hs-CRP>4.5mg/L could detect ruptured plaque with a sensitivity of 91.7% and a specificity of 77.8%. CONCLUSIONS: OCT detected plaque rupture and TCFA more frequent in ACS patients compared with SAP. Elevated hs-CRP and IL-18 were positively related to plaque instability and rupture.

Inverse relation of C-reactive protein levels to heart rate variability in patients after acute myocardial infarction.

INTRODUCTION: Inflammation has a major role in atherosclerosis and the acute phase C-reactive protein (CRP) is elevated after acute myocardial infarction. Inflammation is also implicated in autonomic nervous system control. Heart rate variability (HRV) has been used as a marker of abnormal autonomic activity after myocardial infarction. Our purpose was to investigate the relation between CRP levels and autonomic tone in patients after acute ST-segment elevation myocardial infarction. METHODS: We studied prospectively 98 patients. CRP and the cardiac enzymes CK, CK-MB, and troponin-I were measured for a total of 72 hours and 24-hour Holter ECG recordings for HRV analysis were acquired before hospital discharge. RESULTS: The natural logarithm of CRP levels was inversely correlated with the following logarithmic transformed indices of HRV in the time and in the frequency domain: SDNN, standard deviation of all normal R-R intervals, (r = -0.40, p < 0.001); SDANN index, standard deviation of the average normal R-R intervals for 5-minute segments, (r = -0.46, p < 0.001); SDNN index, mean of the standard deviation of all normal R-R intervals for 5-minute segments (r = -0.41, p < 0.001); total power (TP) (r = -0.38, p < 0.001); high frequency power (HF) (r = -0.31, p < 0.01); low frequency power (LF) (r = -0.45, p < 0.001). The strong inverse relation between CRP and SDNN, SDANN, SDNN index, LF and TP persisted after adjustment for left ventricular function. CONCLUSIONS: Increased levels of circulating CRP after acute myocardial infarction are associated with attenuated HRV indices, suggesting a possible relationship between inflammation and cardiac autonomic balance.

Background diet influences the anti-inflammatory effect of alpha-linolenic acid in dyslipidaemic subjects.

Long-chain n-3 PUFA from fish oils are known to have anti-inflammatory effects. We evaluated the effect of alpha-linolenic acid (ALA), precursor of n-3 fatty acids, on serum inflammatory markers and soluble cellular adhesion molecules (sCAM) of dyslipidaemic males, relative to their background diet. Participants were assigned to two groups, based upon food intake patterns: (a) twenty-one dyslipidaemic subjects who habitually ate a Mediterranean-Cretan-type diet; (b) nineteen dyslipidaemic subjects who normally ate a Westernised Greek diet. All were supplemented with 8.1 g ALA/d for 12 weeks. We determined serum amyloid A (SAA), C-reactive protein (CRP), macrophage colony-stimulating factor (MCSF), IL-6, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 and soluble E-selectin concentrations at the beginning and the end of the ALA supplementation period. Serum baseline concentrations of inflammatory markers and sCAM were similar across the diet groups. Type of diet had a significant impact on the response of inflammatory markers to ALA supplementation. The Westernised Greek diet group showed a reduction in SAA (P<0.001), CRP (P=0.002), MCSF (P=0.005) and IL-6 (P=0.04) concentrations. The Mediterranean-Cretan-type background diet group showed a significant reduction only in MCSF concentrations (P=0.003). The sVCAM-1 concentrations were significantly reduced in both the Westernised Greek diet group (P=0.001) and the Mediterranean-Cretan-type diet group (P<0.001). The present study demonstrated that ALA supplementation lowered the serum concentrations of inflammatory markers more profoundly when the background diet was rich in saturated fatty acids and poor in MUFA.

The effect of diet enriched with alpha-linolenic acid on soluble cellular adhesion molecules in dyslipidaemic patients.

BACKGROUND: Leukocyte adhesion and transendothelial migration, the critical pathogenic components in the development of atherosclerotic lesions, are largely mediated by cellular adhesion molecules (CAMs). We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of soluble forms of CAMs in dyslipidaemic patients. METHODS: We recruited 90 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=60) or to 15 ml of safflower oil (rich in linoleic acid [LA, 18:2n-6]) per day (n=30). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 12 weeks. Blood lipids, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) were measured. RESULTS: Dietary supplementation with ALA significantly decreased sVCAM-1 levels (median decrease 18.7% [577.5 ng/ml versus 487 ng/ml, P=0.0001]). In the LA supplemented group, sVCAM-1 was also significantly decreased but to a lesser extent (median decrease 10.6% [550.5 ng/ml versus 496 ng/ml, P=0.0001]). After controlling for smoking habits, no significant difference was observed in the reduction of sVCAM-1 levels between the two treatment arms (P=0.205). The decrease of sVCAM-1 was independent of lipid changes in both groups. CONCLUSIONS: Dietary supplementation with ALA for 12 weeks significantly decreases sVCAM-1 levels in dyslipidaemic patients. This effect presents a potential mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in the prevention of coronary artery disease. In addition, dietary supplementation with LA significantly decreases sVCAM-1 levels, an effect which requires further investigation.

Preinfarction angina does not alter infarct size and in hospital outcome after acute myocardial infarction with ST elevation.

BACKGROUND: Preinfarction angina has been reported to limit infarct size, in a manner analogous to experimental preconditioning. However, other studies have reported inconsistent results. We aimed to investigate prospectively the role of preinfarction angina on infarct size and in hospital outcome. METHODS: Ninety-nine patients were divided into three groups according to the timing of angina: the group "< 48 h" reported angina within the last 48 h, the group "> 48 h" earlier than 48 h and the group "acute" no angina before infarction. Myocardial injury was estimated by creatine kinase, creatine kinase-MB, troponin I and C-reactive protein. In hospital events included death, recurrent ischemia, congestive heart failure and atrioventricular block. RESULTS: Clinical characteristics, thrombolysis administration and the magnitude of enzymes released were not statistically different among the three groups: peak creatine kinase was 2139+/-1714 U/l for the >48 h group, vs. 2344+/-1634 U/l for the acute group, vs. 2209+/-1384 U/l for the <48 h group (p=0.88). Peak creatine kinase-MB was 124+/-104 U/l for the >48 h group, vs. 168+/-182 U/l for the acute group, vs. 154+/-108 U/l for the <48 h group (p=0.62). Peak troponin I, peak C-reactive protein and in hospital outcome also did not differ statistically in the three groups; p=0.5, p=0.45. CONCLUSIONS: Infarct size estimated by cardiac enzymes and by the marker of C-reactive protein, as well as in hospital clinical prognosis are not different in patients with and without preinfarction angina. It seems, therefore, that preinfarction angina confers ischemic conditions inadequate to mimic preconditioning.

Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients.

BACKGROUND: Inflammation plays an important role in the pathogenesis of coronary artery disease. We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of inflammatory markers in dyslipidaemic patients. METHODS: We recruited 76 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=50) or to 15 ml of safflower oil (rich in linoleic acid (LA, 18:2n-6)) per day (n=26). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 3 months. Blood lipids and C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) levels were determined prior and after intervention. CRP and SAA were measured by nephelometry and IL-6 by immunoassay. RESULTS: Dietary supplementation with ALA decreased significantly CRP, SAA and IL-6 levels. The median decrease of CRP was 38% (1.24 vs. 0.93 mg/l, P=0.0008), of SAA 23.1% (3.24 vs. 2.39 mg/l, P=0.0001) and of IL-6 10.5% (2.18 vs. 1.7 pg/ml, P=0.01). The decrease of inflammatory markers was independent of lipid changes. Dietary supplementation with LA did not affect significantly CRP, SAA and IL-6 concentrations but decreased cholesterol levels. CONCLUSIONS: Dietary supplementation with ALA for 3 months decreases significantly CRP, SAA and IL-6 levels in dyslipidaemic patients. This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease.