Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH.

AIMS: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. METHODS: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. RESULTS: A total of 541 adult patients (249 males) with possible/probable/definite FH heterozygous FH (HeFH) were included (mean age 48.5 ± 15.0 years at registration, 40.8 ± 15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of ASCVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p = 0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5, 13.4 and 19.8%, respectively (p = 0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3, 12.2 and 16.1%, respectively; p = 0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. CONCLUSIONS: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with possible/probable/definite HeFH.

Prevalence of Non-coronary Heart Disease in Patients with Familial Hypercholesterolemia: An Analysis from the HELLAS-FH.

AIMS: Despite the established link between familial hypercholesterolemia (FH) and increased risk of coronary heart disease (CHD), its association with other common atherosclerotic and metabolic diseases has not been extensively studied. The aim of this study was to report the prevalence of peripheral arterial disease (PAD) [i.e., common carotid artery disease (CCAD) and lower extremity arterial disease (LEAD)], aortic valve stenosis, chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in patients with FH. MATERIALS & METHODS: This was a cross-sectional study retrieving data from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). RESULTS: A total of 1,633 adult patients (850 males) with heterozygous FH (HeFH) were included (mean age 51.3±14.6 years at registration and 44.3±15.9 years at diagnosis). Any common carotid artery stenosis (CCAS) was diagnosed in 124 out of 569 patients with available related data (21.8%), while the prevalence of CCAD (defined as a CCAS ≥50%) was 4.2%. The median (interquartile range - IQR) CCAS was 30% (20-40), whereas the median (IQR) carotid intima-media thickness (CIMT) was 0.7 (0.1-1.4) mm. LEAD was reported in 44 patients (prevalence 2.7%). The prevalence of aortic valve stenosis and CKD was 2.0% and 6.4%, respectively. NAFLD was present in 24% of study participants. CONCLUSION: HeFH is associated with a relatively high prevalence of any CCAS and CCAD. The prevalence of LEAD, CKD and aortic valve stenosis was relatively low, whereas the prevalence of NAFLD was similar to that of the general population.

Antiplatelet treatment in diabetic patients with acute coronary syndrome undergoing percutaneous coronary intervention: a GReek AntiPlatElet registry substudy.

BACKGROUND AND AIMS: We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry. PATIENTS AND METHODS: GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed. RESULTS: Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38. CONCLUSION: In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.

Comparison of the antiplatelet effect of clopidogrel hydrogenosulfate and clopidogrel besylate in patients with stable coronary artery disease.

It is well known that patients with poor response to antiplatelet therapy are most likely to have more thrombotic events. Clopidogrel hydrogensulfate (CHS) is a thienopyridine acting as an important antiplatelet agent alone or in combination with acetylsalicylic acid to prevent cardiovascular complications. A different clopidogrel salt, clopidogrel besylate (CB), was recently approved as a generic drug for the same purpose while data about its antiplatelet effect are very scarce. Our study compared the antiplatelet effect of CHS and CB in patients with stable coronary artery disease. Patients with stable coronary artery disease (n = 101) (coronary lesions defined angiographically 30-70 %) were randomized to either CHS (n = 50) or CB (n = 51). After randomization a 600 mg loading dose of the drug was given and monitoring of antiplatelet effect was done 12-14 h later with VerifyNow assay. Antiplatelet response was measured with P2Y12 reaction units (PRU) and % inhibition P2Y12 from baseline (% inhibition P2Y12). Moreover CYP2C19*2, CYP2C19*3 and CYP3Α5 polymorphisms were studied in all patients. Clinical characteristics were similar between the two study groups. No significant difference was observed for baseline platelet reactivity between CHS and CB patients (258 ± 38 vs. 256 ± 38 respectively, p = 0.79). No difference was found for antiplatelet response between the CHS and the CB group, assessed by PRU (195 ± 74 vs. 204 ± 67 respectively, p = 0.51) and by % inhibition P2Y12 (24 ± 25 vs. 24 ± 22 % respectively, p = 0.95). Number of heterozygotes for CYP2C19*2 polymorphism was comparable and their platelet reactivity was similar between the two study groups. Our results indicate that both CB and CHS had an identical antiplatelet effect in patients with stable coronary artery disease. No difference on platelet reactivity of heterozygotes for CYP2C19*2 polymorphism was found between the two study groups.

The "crush" technique as a therapeutic approach for a bifurcation lesion in a saphenous venous graft.

Bifurcation lesions of native coronary arteries are common in daily practice and different strategies for percutaneous coronary intervention have been suggested for their treatment. The "crush" technique, with the use of drug-eluting stents in both the main and the side branch, is a relatively simple procedure that ensures complete lesion coverage, even for bifurcations that have extensive disease within the side branch. We present the case of a bifurcation lesion in a Y-shaped saphenous venous graft in a patient who had previously undergone coronary artery bypass graft surgery. The literature lacks reports regarding the management of such patients. Implementation of the "crush" technique in the specific case resulted in a satisfactory angiographic and long-term clinical outcome.

Oxidative stress changes after stent implantation: a randomized comparative study of sirolimus-eluting and bare metal stents.

BACKGROUND: Although oxidative stress plays an important role in the pathophysiology of restenosis, its role following the implantation of sirolimus-eluting stents (SES) is unknown. METHODS: We examined the relation between total peroxides (TP), a marker of oxidative stress, and in-stent late luminal loss over a 6-month follow-up in patients with stable coronary artery disease and compared the results from SES with those from bare metal stents (BMS). We enrolled 75 consecutive patients, who underwent successful PCI and were randomly allocated to SES (n=37) or BMS (n=38). Blood samples were taken 24 h before, at 24 h, 48 h and 1 month after angioplasty; levels of TP were determined on each occasion. Follow-up coronary angiography was performed 6-8 months later. RESULTS: TP levels in the BMS group were significantly higher at 24 h and 48 h compared to baseline (p=0.006 for both). At one month there was a significant decline from the 48 h levels (p=0.029) to levels slightly, but not significantly higher than baseline. In contrast, in SES TP levels showed no significant changes during the first 48 h, while they declined to levels somewhat lower than baseline at 30 days. A significant correlation was found between TP changes and in-stent late luminal loss at 6 months in both groups. CONCLUSION: Our study showed that patients with stable coronary artery disease who received SES have a different behavior of oxidative stress after stenting compared with BMS, and this could contribute to the difference in restenosis rate between these 2 types of stents.

Isolated atrial microvascular dysfunction in patients with lone recurrent atrial fibrillation.

OBJECTIVES: The purpose of this study was to assess atrial myocardial perfusion in patients with lone recurrent atrial fibrillation (LRAF). BACKGROUND: Although acute atrial ischemia has been implicated in the pathogenesis of atrial fibrillation, there are few data concerning human atrial myocardial perfusion and none for patients with LRAF. METHODS: Sixteen patients with LRAF and 15 control subjects with suitable coronary anatomy underwent time-averaged peak coronary blood flow velocity (APV) measurements (cm/s), using a Doppler guidewire in the proximal left circumflex coronary artery (LCx) and in the left atrial circumflex branch (LACB), at baseline (b) and after adenosine administration to achieve maximal hyperemia (h). Coronary flow reserve was defined as h-APV/b-APV. RESULTS: Although there were no statistically significant differences in b-APV between patients with LRAF and control subjects or between the LACB and LCx, there were significant group (p = 0.002), artery (p = 0.001), and interaction (p < 0.001) effects at maximal hyperemia. In patients with LRAF, the h-APV and coronary flow reserve of the LACB (30.4 +/- 9.5 cm/s and 2.2 +/- 0.4, respectively) were significantly lower than in the LACB of the control subjects (45.8 +/- 12.8 cm/s [p < 0.001] and 2.9 +/- 0.5 [p = 0.001], respectively) or in the patients' LCx (43.0 +/- 10.9 cm/s [p = 0.001] and 3.1 +/- 0.6 [p < 0.001], respectively). CONCLUSIONS: This study confirms for the first time isolated atrial myocardial perfusion abnormalities in patients with LRAF and coronary flow reserve impairment, indicating that microvascular dysfunction is a pathophysiological substrate associated with this arrhythmia.

Vascular endothelial growth factor protein levels and gene expression in peripheral monocytes after stenting: a randomized comparative study of sirolimus: eluting and bare metal stents.

AIMS: Although previous studies have indicated that vascular endothelial growth factor (VEGF) plays an important role in the vascular-healing process after stent implantation, its effect on in-stent restenosis is unclear. We assessed VEGF serum protein levels and gene expression in peripheral monocytes in relation to in-stent restenosis after implantation of sirolimus-eluting (SES) and bare metal stents (BMS) in a non-blinded, randomized study. METHODS AND RESULTS: Forty-two patients (28 men, age 62 +/- 11 years) with stable angina, who underwent elective single-vessel percutaneous coronary intervention, were randomized to SES (n = 21) or BMS (n = 21) implantation. VEGF protein levels in the BMS group showed an increasing trend (P = 0.083), whereas in the SES group they decreased significantly (P = 0.002). BMS induced up-regulation of VEGF mRNA levels, whereas for SES down-regulation was observed. There was no correlation between serum levels and late luminal loss. A significant correlation was found between VEGF gene expression and late luminal loss in both groups (BMS: r = 0.98, P < 0.001; SES: r = 0.65, P = 0.002). CONCLUSION: SES, in comparison with BMS, results in lower VEGF protein levels and gene expression in peripheral monocytes. The latter shows a positive relationship with in-stent late-luminal loss, suggesting an essential role in the reduced in-stent restenosis seen in SES.

Acute effect of esmolol intravenously on coronary microcirculation in patients with idiopathic dilated cardiomyopathy.

Although coronary flow reserve (CFR) impairment was correlated with the prognosis of patients with idiopathic dilated cardiomyopathy (IDC) and microvascular ischemia was implicated in the progress of the disease, little is known about the effect of the established therapy with beta blockers on coronary microcirculation. The purpose of this study was to assess the effect of beta(1) blockade on coronary blood flow and CFR in patients with IDC. Fourteen patients with IDC and 10 control subjects underwent time-averaged peak coronary flow velocity (APCFV) measurements (centimeters per second) in the proximal left anterior descending coronary artery at baseline and at maximal hyperemia before and after beta(1) blockade with intravenous esmolol. CFR was defined as APCFV at maximal hyperemia/APCFV at baseline. Although there were no significant differences in APCFV at baseline between patients with IDC and controls, patients with IDC had significantly lower APCFV at maximal hyperemia than controls (54.2 +/- 12.0 vs 75.1 +/- 18.6, p <0.05) and decreased CFR (2.39 +/- 0.38 vs 3.50 +/- 0.54, respectively, p <0.05). After beta(1) blockade, a significant decrease in APCFV at baseline (19.5 +/- 3.7 vs 22.9 +/- 5.0, p <0.05) and enhancement of APCFV at maximal hyperemia (59.5 +/- 13.3 vs 54.2 +/- 12.0, p <0.05) were observed in patients with IDC, but not in control subjects, leading to significant improvement in CFR (3.06 +/- 0.40 vs 2.39 +/- 0.38, p <0.05). In conclusion, patients with IDC had alterations in coronary blood flow and decreased CFR that improved after beta(1) blockade. These alterations in microvascular function, which are partially reversed by beta blockade, may be 1 of the underlying mechanisms that contribute to the improved prognosis of patients with IDC under such therapy.

Endothelial cell function during atrial fibrillation and after restoration of sinus rhythm.

Beat-to-beat variation in blood flow dynamics during atrial fibrillation (AF) has been associated with evidence of endothelial dysfunction. The aim of the present work is to confirm endothelial dysfunction in patients with AF and test the hypothesis that endothelial dysfunction is reversible upon restoration of normal sinus rhythm. Endothelium-dependent (flow-mediated dilation [FMD]) and endothelium-independent (nitroglycerin-mediated dilation [NMD]) vasodilator function of the brachial artery were measured using high-resolution ultrasound in 46 patients with persistent AF who were scheduled for internal electrical cardioversion and in 25 control subjects. In patients who remained in sinus rhythm after cardioversion, these measurements were repeated after 24 hours (n = 32) and 1 month (n = 19). Compared with control subjects, patients (n = 32) showed lower FMD during AF (8.1 +/- 3.6% vs 12.2 +/- 3.2%, respectively, p <0.001) and similar NMD (17.0 +/- 3.5% vs 15.9 +/- 3.1%, respectively, p = 0.21). In 19 patients who remained in sinus rhythm, FMD increased at both 24 hours (8.0 +/- 3.9% vs 10.6 +/- 4.6%, p = 0.015) and 1 month (8.0 +/- 3.9% vs 13.6 +/- 5.3%, p <0.001). In contrast, NMD was not significantly altered at 24 hours or 1 month after sinus rhythm restoration (17.1 +/- 3.9% vs 17.2 +/- 4.0% vs 16.9 +/- 4.1%). In conclusion, AF is associated with impairment in endothelial function that improves after sinus rhythm restoration.

Combined use of aspiration catheter and distal embolisation protection device to facilitate angioplasty of a totally occluded saphenous vein graft.

Angioplasty of totally occluded saphenous vein grafts is a very challenging procedure and the likelihood of distal embolisation and no-reflow is much higher than in any conventional angioplasty. The use of thrombus aspiration and distal protection devices, although not well studied in a large number of patients, has been shown to be quite effective in preventing such complications. In this case we report our satisfactory experience from the combined use of a novel aspiration catheter and a distal protection device for the treatment of a totally occluded saphenous vein graft.

Reduced systemic inflammatory response to implantation of sirolimus-eluting stents in patients with stable coronary artery disease.

Stent implantation causes significant injury to the vascular wall, resulting in inflammatory activation. Although sirolimus-eluting stents (SES) have anti-inflammatory properties, their effect on periprocedural systemic inflammatory response has not been sufficiently investigated. Eighty-one patients with stable coronary artery disease involving severe stenosis of one major epicardial coronary artery underwent coronary angioplasty with stent implantation and randomly received either SES or bare metal stents (BMS). Blood samples were taken 24h before, at 24h, 48 h and 1 month after the angioplasty and levels of high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and monocyte chemoattractant protein-1 (MCP-1) were determined. HsCRP after BMS implantation increased over 24h (p<0.001) and then remained steady, as did IL-6 and IL-1 beta similarly. In contrast, their levels in SES patients decreased to below baseline by the end of the month. MCP-1 levels increased by the end of 1 month (p<0.001) in the BMS group, whereas in SES they steadily decreased, becoming significantly lower than baseline from 48 h (p=0.015). In conclusion, patients with SES exhibit an attenuation of the postprocedural systemic inflammatory activation during a 1-month follow-up after stent implantation. This might partially explain the reduced restenosis rate associated with SES.

Effect of inhaled salbutamol on coronary circulation in humans.

In 12 patients we assessed the effect of inhaled salbutamol on the coronary circulation. According to our results, large doses of salbutamol increase coronary flow, but not in proportion to the needs of the myocardium (as documented by the increase in coronary oxygen extraction), and decrease coronary flow reserve. These effects may have deleterious consequences in patients with coronary artery disease, causing or worsening myocardial ischemia.

Atrial fibrillation is associated with increased neurohumoral activation and reduced exercise tolerance in patients with non-ischemic dilated cardiomyopathy.

OBJECTIVES: To assess atrial fibrillation (AF) associated differences in proinflammatory cytokines, natriuretic peptide levels and exercise capacity in patients with heart failure (HF) secondary to non-ischemic dilated cardiomyopathy (NIDC). METHODS: We studied 147 NIDC patients, mean age 58.3+/-12.5 years, left ventricular (LV) ejection fraction 27.8+/-10.9% and NYHA class II-III. Neurohumoral activation was assessed by measurement of interleukin IL-1, IL-6, tumor necrosis factor-a (TNF-a), its soluble receptors sTNFR I and II, N-terminal atrial (NT-ANP) and -brain (NT-BNP) natriuretic peptide levels, and functional class was assessed by cardiopulmonary exercise test. RESULTS: Forty patients (27.5%) had chronic AF and they did not differ in age, LV ejection fraction or HF duration compared to patients in sinus rhythm (SR). AF was associated with increased levels of IL-6 (p=0.001), TNF-a (p=0.002), sTNFRI (p=0.023), NT-ANP (p<0.001) and NT-BNP (p=0.003), decreased exercise duration (p<0.001) and slightly reduced maximal oxygen consumption at peak exercise (p=0.07) compared to SR patients. No significant differences in cytokine and natriuretic peptide levels or exercise tolerance were noted when patients in AF were compared to the subgroup of SR with restrictive LV filling pattern. Multivariate analysis showed that NT-ANP (p=0.003) and IL-6 (p=0.006) plasma levels were independently associated with the presence of AF in our patient population. CONCLUSION: AF is associated with increased inflammatory state, natriuretic peptide levels and reduced exercise capacity in patients with HF secondary to NIDC. These findings suggest that the presence of AF in HF represents a more advanced stage of the syndrome.

Successful thrombus removal during angioplasty in a patient with acute myocardial infarction using a new aspiration catheter.

We describe the case of a male patient, aged 62 years, with acute myocardial infarction, who underwent primary angioplasty using a new thrombus aspiration catheter in conjunction with the conventional technique. This catheter is easier to use than similar devices available to date and is extremely effective in the removal of large intracoronary thrombi, thus providing protection against distal embolism during angioplasty procedures.

Acute myocardial infarction in a patient with normal coronary arteries after an allergic reaction.

The case is described of a man aged 51 years who, one hour after a coronary angiographic examination that showed coronary arteries without lesions, suffered an acute inferior myocardial infarction as the result of an acute allergic reaction, probably to the iodinated contrast agent that was used. Acute myocardial infarction following an allergy is an extremely rare clinical entity that, according to existing data, is due to the local release of vasoconstrictive substances as a result of the allergic reaction.

Regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to assess regional coronary flow and contractile reserve in patients with idiopathic dilated cardiomyopathy (IDCM). BACKGROUND: Although IDCM has been associated with alterations in coronary blood flow and contractile reserve, little is known about their regional distribution and correlation. METHODS: Fourteen patients with IDCM and 11 control subjects underwent coronary flow velocity (APV) measurements in the left anterior descending (LAD), left circumflex (LCx), and right coronary (RCA) arteries at baseline (b) and at maximal hyperemia (h). Coronary flow reserve (CFR) was defined as h-APV/b-APV. Wall thickening was assessed in 16 segments (7 assigned to LAD, 5 to LCx, and 4 to RCA) both at rest and under peak stress during low-dose dobutamine echocardiography. Regional contractile reserve was defined as the percentage difference in wall motion score index between rest and stress in each vascular territory. RESULTS: Although there were no significant differences in b-APV, patients with IDCM had significantly lower h-APV than controls in all three vascular territories and reduced CFR (LAD: 2.79 +/- 0.43 vs. 3.48 +/- 0.51, p < 0.05; LCx: 2.71 +/- 0.39 vs. 3.36 +/- 0.65, p < 0.05; and RCA: 3.43 +/- 0.55 vs. 4.02 +/- 0.73, p < 0.05). There was also a significant correlation between CFR and the corresponding contractile reserve in the vascular territory of the LAD (r = 0.75, p = 0.002) and the LCx (r = 0.64, p = 0.014). CONCLUSIONS: Patients with IDCM have alterations in regional coronary flow and reduced CFR. Furthermore, the correlation between regional CFR and the corresponding contractile reserve indicates that microvascular dysfunction may have a pathophysiologic role in the evolution of the disease.