Mediterranean diet and prognosis of first-diagnosed Acute Coronary Syndrome patients according to heart failure phenotype: Hellenic Heart Failure Study.

BACKGROUND/OBJECTIVES: Nutrition in secondary prevention of Acute Coronary Syndrome (ACS) is inadequately investigated. We sought to evaluate the role of Mediterranean diet in prognosis of first-diagnosed ACS patients, according to heart failure type. SUBJECTS/METHODS: in 2006-2009, 1000 consecutive patients hospitalized at First Cardiology Clinic of Athens with ACS diagnosis were enrolled in the study. In 2016, 10-year follow-up was performed (75% participation rate). Only n=690 (69%) first-diagnosed ACS patients were included. Adherence to Mediterranean diet was assessed through MedDietScore (range 0-55). Heart failure phenotypes were reduced, mid-range and preserved ejection fraction (that is, HFrEF, HFmrEF and HFpEF, respectively). RESULTS: Ranking from first to third MedDietScore tertile, fewer 1, 2 and 10-year fatal/non-fatal ACS events were observed. Multivariate logistic regression analysis highlighted a significantly inverse association between MedDietScore and long-term ACS prognosis in 1 year (odds ratio (OR)=0.84, 95% confidence interval (CI) (0.71, 1.00), P=0.05), 2 year (OR=0.91, 95% CI (0.82, 1.00), P=0.04) and 10 year (OR=0.93, 95% CI (0.85, 1.00), P=0.05) follow-up. Further analysis revealed that MedDietScore differentially affected patients' prognosis according to heart failure phenotype, with short-term impact in HFrEF and HFmrEF patients yet longer positive outcomes in HFpEF and C-reactive protein potentially mediated these relations. CONCLUSIONS: Mediterranean diet seemed to protect against recurrent cardiac episodes in coronary patients with major ACS complications. Results were more encouraging with regard to patients with preserved left ventricle function. Such findings may possess a cost-effective, supplementary-to-medical, treatment approach in this patient category where evidence concerning their management are inconclusive.European Journal of Clinical Nutrition advance online publication, 23 August 2017; doi:10.1038/ejcn.2017.122.

Impact of metabolic syndrome on clinical outcomes after new generation drug-eluting stent implantation: the 'obesity paradox' phenomenon is still apparent.

BACKGROUND AND AIM: New generation drug-eluting stents (DES) have improved clinical outcomes. However, their impact on patients with metabolic syndrome (MS) is still unclear as there is no sufficient data. Therefore, we evaluated the impact of the new generation DES on patients with an isolated lesion in the proximal segment of the left anterior descending artery (pLAD) suffering from MS. METHODS AND RESULTS: We evaluated 511 patients with a pLAD lesion. Of these, 147 patients had MS. The major adverse cardiac events (MACE) including death, non-fatal myocardial infarction (MI) and target lesion revascularization (TLR) were defined as primary end points. Stent thrombosis was also evaluated. MACEs had a trend to be higher in non-MS group (8.24% vs 3.40%, p = 0.05) during 20 months mean follow-up period. Rates of cardiac death (1.37% vs 0.68%, p = 0.67), non-fatal MI (1.92% vs 0.0%, p = 0.20), TLR (4.94% vs 2.04% MS, p = 0.21) and thrombosis (3.29% vs 1.36%, p = 0.36) were not significantly different in non-MS and MS group. The Kaplan-Meier curve revealed: MS group: 96.59% vs non-MS group: 91.75% (p = 0.04). MS was a favorable independent predictor for MACE (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.12-0.93, p < 0.03). In addition, independent predictors for MACE were BMI ≥ 30 kg/m(2) (HR 0.87 95% CI 0.79-0.96 p = 0.008) and diabetes mellitus (HR 2.01 95% CI 0.99-4.11, p = 0.05). CONCLUSION: The 'obese paradox' phenomenon is found in the era of new generation DES. In order to investigate the underlying mechanism for this phenomenon further studies are required.

The role of microRNAs in cardiovascular disease.

Cardiovascular disease, which is multifactorial and can be influenced by a multitude of environmental and heritable risk factors, remains a major health problem, even though its pathophysiology is far from been elucidated. Discovered just over a decade ago, microRNAs comprise short, non-coding RNAs, which have evoked a great deal of interest, due to their importance for many aspects of homeostasis and disease. Hundreds of different microRNAs are constantly being reported in various organisms. According to a growing body of literature, they have been implicated in the regulation of human physiological processes. More specifically, miRNAs are expressed in the cardiovascular system and could have crucial roles in normal development and physiology, as well as in disease development. Furthermore, they have been shown to participate in cardiovascular disease pathogenesis including atherosclerosis, coronary artery disease, myocardial infarction, heart failure and cardiac arrhythmias. In contrast to our original thought, miRNAs exist in circulating blood and are relatively stable, thus, they could be proved useful as biomarkers in that state. Understanding the underlying mechanisms, in which these major regulatory gene families are implicated, will provide novel opportunities for diagnosis and therapy of cardiovascular diseases.

Myocardial structure and matrix metalloproteinases.

Metalloproteinases (MMPs) are enzymes which enhance proteolysis of extracellular matrix proteins. The pathophysiologic and prognostic role of MMPs has been demonstrated in numerous studies. The present review covers a wide a range of topics with regards to MMPs structural and functional properties, as well as their role in myocardial remodeling in several cardiovascular diseases. Moreover, the clinical and therapeutic implications from their assessment are highlighted.

Subendocardial viability ratio as an index of impaired coronary flow reserve in hypertensives without significant coronary artery stenoses.

Subendocardial viability ratio (SEVR), calculated through pulse wave analysis, is an index of myocardial oxygen supply and demand. Our aim was to evaluate the relationship between coronary flow reserve (CFR) and SEVR in 36 consecutive untreated hypertensives (aged 57.9 years, 12 males, all Caucasian) with indications of myocardial ischaemia and normal coronary arteries in coronary angiography. CFR was calculated by a 0.014-inch Doppler guidewire (Flowire, Volcano, San Diego, CA, USA) in response to bolus intracoronary administration of adenosine (30-60 µg). SEVR was calculated by radial applanation tonometry, while diastolic function was evaluated by means of transmitral flow and tissue Doppler imaging. Hypertensive patients with low CFR (n=24) compared with those with normal CFR (n=12) exhibited significantly decreased SEVR by 24.5% (P=0.002). In hypertensives with low CFR, CFR was correlated with SEVR (r=0.651, P=0.001). After applying multivariate linear regression analysis, age, left ventricular mass index, Em/Am, 24-h diastolic blood pressure (BP) and SEVR turned out to be the only independent predictors of CFR (adjusted R(2)=0.718). Estimation of SEVR by using applanation tonometry may provide a reliable tool for the assessment of coronary microcirculation in essential hypertensives with indications of myocardial ischaemia and normal coronary arteries.

Divergent anti-inflammatory effects of different oil acute consumption on healthy individuals.

BACKGROUND/OBJECTIVES: Inter-cellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and tumor necrosis factor-α (TNF-α), are implicated in atherogenesis. In addition, several types of oil as part of different types of diet are associated with the initiation of atherosclerosis and consequently with the risk of cardiovascular disease. However, the exact role of oil consumption on vascular inflammation remains unknown. In this parallel study, we assessed the acute effects of extra virgin olive oil, soy oil, corn oil and cod liver oil on circulating soluble(s) forms of adhesion molecules and TNF-α. SUBJECTS/METHODS: In all, 67 healthy volunteers were randomized to receive 50 ml of oil. Soluble forms of VCAM-1, ICAM-1 and TNF-α were measured by enzyme-linked immunosorbent assay at baseline and at 3 h post oil consumption. RESULTS: All types of oil had no significant effect on soluble VCAM-1 levels (P=nonsignificant (NS) for all). On the contrary, all oil types decreased ICAM-1 levels (P<0.01). Olive oil (P<0.05), soy oil and cod liver oil (P<0.01 for both) reduced TNF-α levels significantly, in contrast to corn oil, which induced a nonsignificant decrease (P=NS). Moreover, there was a significant correlation between the absolute change in ICAM-1 and TNF-α levels (ρ=0.379, P<0.05), but not between the absolute changes in VCAM-1 and TNF-α levels (ρ=0.019, P=NS). CONCLUSIONS: Acute consumption of all types of oil decreased significantly ICAM-1 levels. In addition, olive oil, soy oil and cod liver oil decreased significantly TNF-α levels. Moreover, the absolute change in TNF-α levels was correlated with the absolute change in ICAM-1 levels. These findings indicate that acute consumption of specific types of oil is associated with specific significant anti-inflammatory effects.

Endothelial dysfunction: potential clinical implications.

Vascular endothelium is responsible for the secretion of several substances exerting anti-atherogenic effects. Endothelial damage is also crucial for the progress of atherosclerosis and risk factors for atherosclerosis represent crucial factors associated with endothelial dysfunction. Studies have shown that patients with cardiovascular disease are characterized by impaired endothelial function (EF). Therefore, several agents have been proposed as potential modulators of EF. Most of the available approaches include pharmaceutical agents routinely used such as statins, angiotensin converting enzyme inhibitors, antioxidants, L-arginine, insulin sensitizers or others still under investigation such as tetrahydrobiopterin or folic acid (folate). Despite of the fact that there are several strategies aiming to improve endothelial dysfunction by enhancing nitric oxide bioavailability, it is still unclear whether they could be beneficial at a clinical level.

Prognostic clinical and angiographic characteristics for the development of a new significant lesion in remote segments after successful percutaneous coronary intervention.

BACKGROUND: The majority of cardiovascular events in patients undergoing PCI arise from the progression of NCL during the long-term follow-up period. The purpose of the study was to investigate the clinical and angiographic factors related to the progression of non-culprit lesions (NCL) of patients undergoing percutaneous coronary interventions (PCI). METHODS: One hundred and seventeen patients that underwent two coronary angiograms with a time interval greater than 3 months were enrolled. All patients underwent PCI as a treatment for the culprit lesion. In the second coronary angiography we investigated whether they had a new culprit lesion clearly differentiated from the one of the first angiogram. The demographic characteristics, the clinical syndrome responsible for the first PCI and the procedural characteristics were recorded. Quantitative coronary angiography was performed at the culprit lesion of the second angiography and in the same lesion in the first angiography. RESULTS: Multivariate analysis showed that the independent variables for the development of a significant lesion at the follow-up requiring intervention were: the presence of complex lesion (53.78% vs 36.22%, p<0.001, OR=39.42), acute myocardial infarction (AMI) at the initial diagnosis (36.3% vs 32.4%, p<0.001, OR=3.9), and smoking (46.15% vs 53.84%, p=0.03, OR=0.29). CONCLUSIONS: Patients with AMI and complex morphology of NCL have increased risk for a new intervention after successful PCI. Smoking at the time of the follow up, was associated with fewer coronary interventions.

Impact of type 2 diabetes mellitus on diffuse inflammatory activation of de novo atheromatous lesions: implications for systemic inflammation.

AIMS: Local coronary and systemic inflammation is pronounced in patients with diabetes mellitus (DM). Intracoronary thermography detects local inflammation and C-reactive protein (CRP) is a marker of systemic inflammation. We investigated whether or not, in patients with DM, thermal heterogeneity of culprit lesions (CLs) correlates with that of non-culprit lesions (NCLs) and with systemic inflammation. METHODS: We included DM patients who had two angiographically significant lesions and were undergoing percutaneous coronary intervention. We measured the temperature difference (DeltaT) between the lesion and proximal vessel wall. RESULTS: We included 104 (n=208 lesions) patients: 32 (n=64 lesions) had DM and 72 (n=144 lesions) were non-DM (control group). DeltaT was increased in DM in both CLs and NCLs (CLs: DM=0.12+/-0.06 degrees C; no DM=0.06+/-0.04 degrees C; P<0.01 versus NCLs: DM=0.13+/-0.08 degrees C versus no DM=0.06+/-0.05 degrees C; P<0.01). Patients with DM had similar DeltaT in CLs and NCLs (P=0.49). A linear correlation was detected between heat production in all lesions and CRP (R=0.45; P<0.01), which was attributed to the correlation of DeltaT in lesions of patients with DM and CRP (R=0.32; P<0.01). In lesions of patients with low CRP, a greater rate of discrepancy was found, as 100% of lesions in patients with DM versus 66.1% of lesions of patients without DM had a high DeltaT in one or both lesions (P<0.01). CONCLUSION: In patients with DM, local inflammatory activation is diffuse and correlates with systemic inflammation. However, low systemic inflammatory activation does not always predict an increase in local thermal heterogeneity.

Left ventricular mass but not geometry determines left atrial size in the early stages of hypertension.

We investigated whether the type of left ventricular (LV) geometry is associated with left atrial (LA) size as determined either by LA diameter or by volume, indexed for body surface area, in essential hypertensives. A total of 339 consecutive, untreated, hypertensives (aged 51.8 years, 234 males) underwent 24-h ambulatory blood pressure (BP) monitoring and estimation of LA diameter and volume, as well as LV structure and function by echocardiography. LV hypertrophy was present in 130 (38.3%) patients whereas normal geometry (LV-NG), concentric remodeling (LV-CR), concentric hypertrophy (LV-CH) and eccentric hypertrophy (LV-EH) represented 34.5, 27.1, 25.7 and 12.7%, respectively. Patients with either LV-CH or LV-EH had increased LA diameter index compared with those with either LV-NG (by 1.1 mm m(-2), P<0.01 and 1.4 mm m(-2), P=0.003, respectively) or LV-CR (by 1.3 mm m(-2), P=0.003 and 1.6 mm m(-2), P=0.001, respectively). Similarly, patients with either LV-CH or LV-EH had significantly increased LA volume index compared with those with either LV-NG (by 3.2 ml m(-2), P<0.001 and 3.4 ml m(-2), P<0.005, respectively) or LV-CR (by 4.5 and 4.7 ml m(-2), respectively, P<0.001 for both). Multiple linear regression analysis showed that the independent predictors of both LA volume and diameter index were LV mass index, 24-h pulse pressure and E/Em.LA size assessed either by its diameter or by volume is closely related only to LV mass index and not to any specific LV geometric pattern in the early stages of essential hypertension.

Increased coronary sinus blood temperature: correlation with systemic inflammation.

BACKGROUND: Recent studies have shown that patients with single vessel coronary artery disease (CAD) suffering from acute coronary syndromes (ACS) have increased coronary sinus (CS) blood temperature compared with the right atrium (RA). The aim of this study was to investigate whether there is a correlation between systemic inflammatory indexes and CS temperature and whether there is a difference in CS temperature between patients with single vs. multivessel disease. MATERIALS AND METHODS We included consecutive patients scheduled for coronary angiography for recent-onset chest pain evaluation. We measured C-reactive protein (CRP) levels in the study population. Coronary sinus and RA blood temperature measurements were performed by a 7F thermography catheter. DeltaTau was calculated by subtracting the RA from the CS blood temperature. RESULTS: The study population comprised 53 patients with ACS, 25 patients with stable angina (SA) and 22 subjects without CAD (control group). DeltaTau was greater in patients with ACS and with SA compared with the control group (0.22 +/- 0.10 degrees C, 0.18 +/- 0.04 degrees C vs. 0.14 +/- 0.07 degrees C, P < 0.01 for both comparisons). The ACS group had greater DeltaTau compared with the SA group, although the difference did not reach statistical significance (P = 0.09). Eighteen (39.1%) out of 46 patients with multivessel disease had three-vessel disease and 28 (60.8%) had two-vessel disease. DeltaTau between patients with multivessel and single vessel disease was similar (0.22 +/- 0.01 degrees C, 0.19 +/- 0.01 degrees C, P = 0.17). The levels of CRP were well correlated with DeltaTau (R = 0.35b, P < 0.01). CONCLUSIONS: Systemic inflammation is well correlated with CS temperature; thus, an inflammatory process could be the underlying mechanism for increased heat production from the myocardium.

Statin treatment is associated with reduced thermal heterogeneity in human atherosclerotic plaques.

AIMS: Heat released from atherosclerotic plaques as a result of the local inflammatory process, may be measured in vivo by a thermography catheter. Statins seem to have an antiinflammatory effect which results in plaque stabilization. The aim of this study was to investigate the effect of statins on plaque temperature. METHODS AND RESULTS: The study population included 72 patients: 21 with effort angina, 32 with unstable angina and 19 with acute myocardial infarction. In the study group, 37 patients received statins for more than 4 weeks and 35 were not receiving statins. We measured the temperature difference (deltaT) between the atherosclerotic plaque and the proximal vessel wall (background temperature) using a thermography catheter. The statistical analysis showed that the mean value of deltaT was higher in the untreated group compared to the treated-with-statin, group (0.56+/-0.41 vs 0.29+/-0.33 degrees C, P<0.01). Moreover, a progressive increase in deltaT by type of clinical syndrome was observed in both groups (statin group; effort angina: 0.24+/-0.15, unstable angina: 0.26+/-0.26, acute myocardial infarction: 0.40+/-0.28, vs untreated group; effort angina: 0.41+/-0.26, unstable angina: 0.44+/-0.28, acute myocardial infarction: 0.84+/-0.52, P<0.05). Multivariate analysis showed that treatment with statins was an independent factor in temperature variation, after taking into account the effect of the clinical syndrome (P<0.05). CONCLUSIONS: Patients on statin treatment produce less heat from the culprit coronary lesion than those not treated. Thus, statins seem to have a favourable effect on heat release from atherosclerotic plaques, and whether this effect has an impact on plaque stabilization needs to be investigated in future studies.

Acute effect of clonidine on left ventricular pressure-volume relation in hypertensive patients with diastolic heart dysfunction.

We sought to assess the haemodynamic effects of clonidine on left ventricular (LV) pressure-volume relation in patients with diastolic heart dysfunction due to essential hypertension. Towards this end, simultaneous recordings of LV volume (acoustic quantification) and LV pressure (micromanometer) were obtained in 10 such patients before and after drug administration and compared to baseline findings on 10 matched normal controls. The following measurements and calculations were obtained: maximal positive and negative first derivative of LV pressure (peak +dP/dt and peak -dP/dt, respectively), LV minimal and end-diastolic pressure, peak systolic blood pressure, time constant of relaxation (TAU), LV stroke work and LV stiffness constant. The two invasive indexes, LV stiffness constant and TAU classified 10/10 patients as having abnormal LV diastolic function compared with 7/10 patients so classified by Doppler studies. Central sympathetic suppression by a single oral dose of clonidine 0.125 mg in these patients resulted within 60 min in a decrease of heart rate and mean arterial pressure as well as a significant improvement of LV diastolic function indexes. Specifically, the LV stiffness constant (ml(-1)), in normal subjects was 0.0028 vs 0.0152 (P < 0.001) in hypertensive subjects at baseline, vs 0.0053 in hypertensive after clonidine (P < 0.001 vs baseline). Likewise, the E/A ratio, was 1.08 in normal subjects vs 0.88 (P < 0.0001) in hypertensives at baseline, vs 1.28 in hypertensives after clonidine (P < 0.0001 vs baseline). With clonidine the diastolic portion of the pressure-volume curve was displaced downward. In conclusion, clonidine can improve diastolic dysfunction without depressing systolic LV performance. The improvement may be attributable in part to withdrawal of direct sympathetic influence on the myocardium and in part to the indirect effect of systemic, pulmonary and coronary artery relaxation.

Thermography of human arterial system by means of new thermography catheters.

In this case report, we present the first clinical application of three thermography catheters for temperature measurements in the coronary arteries, the aorta, and the femoral arteries. The entire procedure was performed successfully without complications. Larger clinical studies are required in order to examine the feasibility for the application of the aortic and the peripheral artery thermography catheters and the clinical significance of temperature measurements in these arteries. Cathet Cardiovasc Intervent 2001;54:51-58.

Increased local temperature in human coronary atherosclerotic plaques: an independent predictor of clinical outcome in patients undergoing a percutaneous coronary intervention.

OBJECTIVES: We investigated the midterm clinical significance of human coronary atherosclerotic plaques temperature after a successful percutaneous coronary intervention. BACKGROUND: Previous studies have shown an increased temperature in human atherosclerotic plaques. However, the prognostic significance of atherosclerotic plaque temperature in patients undergoing a successful percutaneous intervention is unknown. METHODS: We prospectively investigated the relation between the temperature difference (deltaT) between the atherosclerotic plaque and the healthy vessel wall and event-free survival among 86 patients undergoing a successful percutaneous intervention. Temperature was measured by a thermography catheter, as previously validated. The study group consisted of patients with effort angina (EA) (34.5%), unstable angina (UA) (34.5%) and acute myocardial infarction (AMI) (30%). RESULTS: The deltaT increased progressively from EA to AMI (0.132 +/- 0.18 degrees C in EA, 0.637 +/- 0.26 degrees C in UA and 0.942 +/- 0.58 degrees C in AMI). The median clinical follow-up period was 17.88 +/- 7.16 months. The deltaT was greater in patients with adverse cardiac events than in patients without events (deltaT: 0.939 +/- 0.49 degrees C vs. 0.428 +/- 0.42 degrees C; p < 0.0001). The deltaT was a strong predictor of adverse cardiac events during the follow-up period (odds ratio 2.14, p = 0.043). The threshold of the deltaT value, above which the risk for an adverse cardiac event was significantly increased, was 0.5 degrees C. The incidence of adverse cardiac events in patients with deltaT > or = 0.5 degrees C was 41%, as compared with 7% in patients with deltaT < 0.5 degrees C (p < 0.001). CONCLUSIONS: Increased local temperature in atherosclerotic plaques is a strong predictor of an unfavorable clinical outcome in patients with coronary artery disease undergoing percutaneous interventions.