Is premorbid stress assessed by hair cortisol concentration linked to Takotsubo syndrome? Results from a pilot study.

INTRODUCTION: The pathophysiology of Takotsubo syndrome (TTS) is not completely understood and the role of chronic stress is among the main mechanistic links. The aim of this study was to explore whether accumulating hair cortisol concentration (HCC), a novel biomarker of chronic stress, is associated with the occurrence of TTS. METHODS: A consecutive series of 18 TTS patients and 36 age and sex matched healthy controls were included in our analysis. Hair samples were collected from participants'' vertex. The proximal 2.5 cm of hair was cut in equal parts of 0.5 cm, reflecting mean cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection. RESULTS: HCC was higher in TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event. The rate of HCC increase was significantly higher in TTS patients versus controls (beta of interaction = 0.48; 95%CI: 0.36-0.60; p < 0.001). CONCLUSIONS: The steadily increasing trend of HCC in TTS patients suggests that the additive effect of multiple stressful events over several weeks prior TTS onset may disrupt cortisol homeostasis and play a role in TTS pathophysiology.

NT-proBNP/cardiac troponin T ratio >7.5 on the second day of admission can differentiate Takotsubo from acute coronary syndrome with good accuracy.

BACKGROUND: Takotsubo syndrome (TTS) is not usually diagnosed until patients with suspected acute coronary syndrome (ACS) and echocardiographically detected apical aneurysm are found to have "normal" coronary angiography (CA). Our aim was to explore whether cardiac biomarkers can contribute to the early diagnosis of TTS. METHODS: Ratios of N-terminal-pro brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT) both expressed in pg/mL [admission and the 3 following days] were compared in 38 patients with TTS and 114 ACS patients of whom 58 had non-ST-elevation myocardial infarction (NSTEMI). RESULTS: NT-proBNP/cTnT ratio at admission and during the following 3 days was significantly higher in TTS compared to patients with ACS [18.4 (8.7-41.7) vs 2.9 (0.8-6.8), 29.6 (14.3-53.7) vs 1.2 (0.5-2.7), 30.0 (11.6-50.9) vs 1.7 (0.5-3.0), 27.8 (11.3-42.6) vs 1.4 (0.6-2.8), respectively, all <0.001]. Βest discrimination of TTS from ACS was possible with the ratio of NT-proBNP/cTnT on the 2nd day. A cut-off value of NT-proBNP/cTnT ratio >7.5 had a sensitivity of 97.3%, a specificity of 95.4% and an accuracy of ∼96% in detecting TTS as opposed to ACS. Furthermore, the ratio of NT-proBNP/cTnT preserved its discriminatory value in the subgroup of patients with NSTEMI. In particular, an NT-proBNP/cTnT ratio >7.5 on the 2nd day had a sensitivity of 97.3%, a specificity of 91.4%, and an accuracy of 93.7% in differentiating TTS from NSTEMI. CONCLUSIONS: An NT-proBNP/cTnT ratio >7.5 on the 2nd day of admission can be useful for the early identification of TTS among selected patients initially presenting with ACS, a ratio more clinically useful in the setting of NSTEMI.

Differential prognostic value of resistin for cardiac death in patients with coronary artery disease according to the presence of metabolic syndrome.

Resistin is associated with atherosclerosis progression by affecting inflammation and insulin resistance. There are controversial data regarding the prognostic value of resistin in stable coronary artery disease (CAD) patients. We prospectively investigated the long-term prognostic value of resistin in patients with stable CAD. A total 741 consecutive patients with stable CAD were followed for a median of 5.5 years. Serum resistin, lipids, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) levels were measured at baseline. Primary endpoints were cardiac death and secondary hospitalizations for acute coronary syndrome, arrhythmic event or ischemic stroke. Follow-up data were obtained from 703 patients of whom 79 had a cardiac death (11.2%) and 205 (29.2%) met the secondary endpoints. Resistin was positively correlated with hsCRP (r = 0.159, p < 0.001) and IL-6 (r = 0.165, p = 0.002), and negatively with high-density lipoprotein-cholesterol (r = - 0.176, p < 0.001). Resistin levels could not predict cardiac death [HR 1.044; 95% CI 0.994-1.096; p = 0.087] neither secondary endpoints [HR 1.025; 95% CI 0.983-1.068; p = 0.250). Among 298 patients (42.4%) with metabolic syndrome (MS) resistin levels were independently associated with cardiac death after adjustment for conventional risk factors [HR 1.121; 95% CI 1.045-1.204; p = 0.002). Further adjustment for ejection fraction of left ventricle (LVEF) did not change the association (HR 1.145; 95% CI 1.057-1.240; p = 0.001). Patients with resistin values ≥ 7.6 ng/mL (median level) had 2.8 times higher risk of cardiac death compared to those with resistin levels < 7.6 ng/mL after adjustment for traditional risk factors and LVEF (HR 2.882; 95% CI 1.311-6.336; p = 0.008). Resistin is independently associated with cardiac death in patients with stable CAD and MS.

Homozygosity of the TT methylenetetrahydrofolate reductase C677T genotype is an independent long-term predictor of cardiac death in patients with premature myocardial infarction.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is the main genetic modulator of homocysteine. Data suggest a potential association of homozygosity for the TT MTHFR genotype with premature myocardial infarction (MI). We explored whether TT homozygosity is associated with long-term prognosis in patients with premature ST-segment elevation MI (STEMI). METHODS: A total of 265 consecutive patients who had survived their first STEMI ≤35 years of age were followed for a median of 8 years (5-12). Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. Serum lipids, homocysteine, folate levels were measured at baseline and all patients were also tested for the MTHFR C677T polymorphism. RESULTS: During follow-up 14 patients died (cardiac death) [5.3%] while 84 (31.7%) met the secondary endpoints. In univariate Cox regression analysis TT homozygosity predicted the occurrence of cardiac death (Hazard ratio (HR): 4.071; 95% confidence interval (CI): 1.404-11.809, p = .010) but not the occurrence of secondary endpoints (HR: 0.877; 95% CI: 0.479-1.605, p = .669). TT homozygosity remained an independent predictor of cardiac death after adjustment for conventional risk factors (i.e., sex, diabetes mellitus, hypertension, family history of premature coronary artery disease [CAD]) [HR: 4.350; 95% CI: 1.472-12.856, p = .008]. The association also remained after adjustment for left ventricular ejection fraction or the presence of significant CAD. CONCLUSIONS: Homozygosity for the TT MTHFR is an independent long-term predictor of cardiac death in patients with premature STEMI.

Hyperhomocysteinemia as the only risk factor in a young man presenting with ST-elevation myocardial infarction.

Hyperhomocysteinemia has been established as a risk factor for cardiovascular events. This case of a 23-year-old male, presenting with acute coronary thrombosis and unremarkable past medical history, highlights the importance of measuring homocysteine levels in young individuals with acute coronary syndromes, especially those without conventional risk factors. .

Myocardial infarction or acute coronary syndrome with non-obstructive coronary arteries and sudden cardiac death: a missing connection.

Myocardial infarction with non-obstructive coronary arteries or any acute coronary syndrome (ACS) with normal or near-normal (non-obstructive) coronary arteries (ACS-NNOCA) is an heterogeneous clinical entity, which includes different pathophysiology mechanisms and is challenging to treat. Sudden cardiac death (SCD) is a catastrophic manifestation of ACS that is crucial to prevent and treat urgently. The concurrence of the two conditions has not been adequately studied. This narrative review focuses on the existing literature concerning ACS-NNOCA pathophysiology, with an emphasis on SCD, together with risk and outcome data from clinical trials. There have been no large-scale studies to investigate the incidence of SCD within ACS-NNOCA patients, both early and late in the disease. Some pathophysiology mechanisms that are known to mediate ACS-NNOCA, such as atheromatous plaque erosion, anomalous coronary arteries, and spontaneous coronary artery dissection are documented causes of SCD. Myocardial ischaemia, inflammation, and fibrosis are probably at the core of the SCD risk in these patients. Effective treatments to reduce the relevant risk are still under research. ACS-NNOCA is generally considered as an ACS with more 'benign' outcome compared to ACS with obstructive coronary artery disease, but its relationship with SCD remains obscure, especially until its incidence and effective treatment are evaluated.

Homocysteine is an independent predictor of long-term cardiac mortality in patients with stable coronary artery disease in the era of statins.

BACKGROUND: Homocysteine (Hcy) is considered a risk factor for cardiovascular disease. OBJECTIVE: To explore the long-term prognostic value of Hcy in patients with stable coronary artery disease (CAD) in the era of statins. METHODS: A total of 876 consecutive patients with stable CAD were recruited and followed up for a median of 6.1 years. Lipids and Hcy levels were measured at baseline. Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. RESULTS: Follow-up data were obtained from 842 patients of whom 70 had a cardiac death (8.3%), while 258 (30.6%) met the secondary endpoints. Seven hundred four patients (83.6%) were on statins. In univariate Cox regression analysis Hcy predicted the occurrence of cardiac death [hazard ratio: 1.030; 95% confidence interval (CI): 1.018-1.042, P < 0.001] but not the occurrence of secondary endpoints (hazard ratio: 1.010; 95% CI: 0.999-1.020, P = 0.081). Hcy remained an independent predictor of cardiac death after adjustment for conventional risk factors, ejection fraction and statin use (hazard ratio: 1.030; 95% CI: 1.017-1.044, P < 0.001). Patients in the highest tertile of Hcy levels (>14.1 µmol/L) had three times higher risk of cardiac death compared with patients in the lowest tertile (<10.3 µmol/L) (hazard ratio = 3.036, CI: 1.983-4.649, P < 0.001). CONCLUSION: Hcy is an independent predictor of cardiac death in patients with stable CAD in the era of statins.

PCSK9 inhibitors in clinical practice: Novel directions and new experiences.

BACKGROUND: In randomized clinical trials, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein-cholesterol (LDL-C) with a favorable tolerability and safety profile. Our purpose is to provide real-world data regarding the indications, efficacy and safety of PCSK9i. METHODS: The cohort comprised 141 patients who attended the lipid clinic of 3 hospitals in Greece and started using PCSK9i. Patients were requested to attend the lipid clinic at 3 months and at 1 year. RESULTS: Ninety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). A PCSK9i [evolocumab 140 mg/2 weeks (n = 82), alirocumab 75 mg/2 weeks (n = 46) and alirocumab 150 mg/2 weeks (n = 13)] was prescribed due to failure to achieve LDL-C targets despite maximum lipid-lowering therapy (LLT) in 75% of patients, while in the remaining cases, the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2% and remained constant at 12 months (55.8% reduction from baseline). LDL-C target was achieved by 68.1% of patients at 3 months. "Totally" intolerant to statins patients (unable to tolerate any statin dose, n = 23) showed the lowest LDL-C reduction (47.7%). Side effects attributed to treatment were reported by 14 patients (10%). The total number of patients who stopped PCSK9i at 1 year was 14 (10%) but only 2 (1.4%) discontinued treatment because of side effects (myalgias). CONCLUSIONS: Our real-world results of PCSK9i showed comparable efficacy and tolerability to those reported in clinical trials and highlighted the value of treatment with PCSK9i heFH patients not achieving LDL-C targets despite maximum LLT and high or very high risk statin intolerant patients.

Prevalence of heterozygous familial hypercholesterolemia and combined hyperlipidemia phenotype in very young survivors of myocardial infarction and their association with the severity of atheromatous burden.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) and combined hyperlipidemia (CHL) phenotype are associated with premature myocardial infarction (MI). OBJECTIVE: To assess the prevalence of HeFH and CHL phenotype among young survivors of MI and compare patients' characteristics with these 2 lipid disorders. METHODS: We recruited 382 young survivors of MI (≤40 years). Fasting lipids, lipoprotein(a) [Lp(a)], apolipoprotein A-1, and apolipoprotein B (apoB) levels were determined. Using the Dutch Lipid Clinic Network (DLCN) algorithm, patients having definite or probable HeFH were identified. Patients with apoB levels >120 mg/dL and triglyceride levels >170 mg/dL (1.92 mmol/L) [>90th percentile of 326 age and sex-matched healthy controls] were classified as having CHL phenotype. Common carotid artery intima-media thickness (CCA-IMT) was measured by B-mode ultrasonography. RESULTS: Eighty-one patients (21.2%) had definite/probable HeFH and 62 (16.2%) had CHL phenotype. Twenty-three patients fulfilled the criteria for both HeFH and CHL phenotype and were removed from further comparisons. Patients with HeFH (n = 58) had higher levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, Lp(a), and apoB, whereas patients with CHL phenotype (n = 39) had higher levels of triglycerides and lower high-density lipoprotein (HDL)-cholesterol levels. The prevalence of metabolic syndrome was higher in patients with CHL phenotype compared to those with HeFH (67.0% vs 16.4%, P < .001). Patients with HeFH had more extensive coronary artery disease (3-vessel disease: 36.2% vs 12.8%, P = .011) and greater right CCA-IMT (0.67 ± 0.11 mm vs 0.56 ± 0.09 mm, P < .001) and left CCA-IMT (0.68 ± 0.10 mm vs 0.56 ± 0.08 mm, P < .001) compared to CHL phenotype patients. CONCLUSIONS: Both HeFH and CHL phenotype are common among patients with premature MI. CHL phenotype compared to HeFH is associated with less atheromatous burden in coronary and carotid arteries at the time of first MI.

Decreased prevalence of mixed cryoglobulinemia in the HAART era among HIV-positive, HCV-negative patients.

There is an established association between human immunodeficiency virus (HIV) infection and mixed cryoglobulinemia, as demonstrated in studies mostly conducted before the introduction of highly active antiretroviral therapy (HAART). To assess the impact of the latter on the cryoglobulinemic status in patients with HIV infection, 133 consecutive, unselected HIV-positive patients, from which only 8 (6%) had co-infection with hepatitis C virus (HCV), were evaluated for the presence of cryoglobulins, according to whether they received or not antiretroviral therapy (ART). Patients shown to be cryoglobulin-positive in a previous study were assessed prospectively, after introducing HAART. Cryoglobulinemia was found in 10 (7.5%) of 133 patients:4 (3.9%) of 101 patients receiving ART versus 6 (18.8%) of 32 patients not receiving ART (P = 0.013). When HCV-positive patients were excluded from the analysis, the correlation between cryoglobulinemia and ART remained significant (P = 0.019). Among 11 previously detected cryoglobulin-positive patients, 8 became cryoglobulin-negative after receiving HAART for a mean period of 6.5 years (P = 0.039). Thus, ART seems to decrease the prevalence of cryoglobulinemia in HIV-infected, HCV-negative patients, a finding which provides indirect evidence of the etiologic role of HIV in the pathogenesis of cryoglobulins.

Reversible dilated cardiomyopathy associated with amphotericin B treatment.

We report two patients, who developed dilated cardiomyopathy and subsequent congestive heart failure after treatment with amphotericin B (AmB). The echocardiographic findings and the symptoms of heart failure resolved after the discontinuation of the drug. The clinical data from our cases and two similar cases reported in the literature suggest that the presence of other factors predisposing to cardiac dysfunction may facilitate the occurrence of this rare side effect.

Fatal nucleoside-associated lactic acidosis in an obese woman with human immunodeficiency virus type 1 infection on a very low-calorie diet.

This study reports the case of an obese woman with human immunodeficiency virus type 1 (HIV-1) infection who developed fatal nucleoside-associated lactic acidosis 10 d after she started a weight-loss dietary regimen containing 600 kcal/d. This case suggests that very low-calorie diets may be life threatening for HIV-infected patients receiving nucleoside analogues.