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.

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.

BACKGROUND: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12­lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.

The association between homocysteine levels, Mediterranean diet and cardiovascular disease: a case-control study.

The aim was to investigate the association between homocysteine (Hcy) and acute coronary syndrome (ACS) and to test the potential moderating role of Mediterranean diet. An age and gender matched case-control study was conducted among 1491 patients with a first ACS event and 3037 adults free of cardiovascular disease (CVD). Adherence to the Mediterranean diet was measured using the MedDietScore (range 0-55). An increase in Hcy levels was associated with a 1% and 3% higher likelihood of ACS among younger (<45 yrs) and middle-aged (45-60yrs) adults (p's < 0.05), but not in older adults (p = 0.13). Moreover, Hcy was associated with 3% (95%CI: 1.01-1.06) increase in the likelihood of ACS among those who did not adhere to the Mediterranean diet. Hence, Hcy is apparently independently associated with ACS among younger and middle-aged individuals. The inverse association between Mediterranean diet adherence and Hcy highlights a disease-preventing effect of the Mediterranean diet on CVD.

Extreme-risk category: High prevalence among stable coronary patients and an emerging widening treatment gap in achieving LDL-cholesterol less than 55 mg/dL.

BACKGROUND AND AIMS: The latest guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) proposed a new "extreme-risk" category of patients, for whom a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dL (1.4 mmol/L) is advised. We aimed to identify the proportion of patients with stable coronary artery disease (CAD), who are at extreme cardiovascular (CV) risk, and explore how achievable is the new LDL-C goal. METHODS: We enrolled 1629 consecutive patients ≤80 years with stable CAD. Fasting lipids were determined and patients having probable or definite heterozygous familial hypercholesterolaemia (HeFH) were identified using the Dutch Lipid Clinic Network algorithm. RESULTS: The prevalence of risk factors/characteristics suggesting an extreme CV risk were as follows: 32% diabetes mellitus, 33% premature CAD and 9.2% HeFH. In total, 895 (55%) patients had at least one of those risk factors/characteristics and formed the extreme CV risk category. Among patients at extreme risk, 87% were on lipid-lowering therapy, of whom 20.3% had LDL-C <70 mg/dL (1.8 mmol/L) and only 5.3% had LDL-C <55 mg/dL. CONCLUSIONS: More than half of all patients with stable CAD are at extreme CV risk and very few (∼5%) achieve LDL-C levels <55 mg/dL. Using maximally-tolerated high-intensity statin combined with ezetimibe, if necessary, is imperative to bridge the treatment gap, while in selected cases the addition of PCSK9 inhibitors will be required.

High levels of lipoprotein (a) and premature acute coronary syndrome.

BACKGROUND AND AIMS: High levels of lipoprotein(a) [Lp(a)] are associated with increased risk of acute coronary syndrome (ACS). We explored whether Lp(a) exhibits a stronger association with premature ACS. METHODS: A case-control study was conducted; 1457 patients with a history of ACS (54.8 ± 13 years, 86% males) and 2090 age-sex matched adults free of cardiovascular disease were enrolled. Bio-clinical characteristics [risk factors, low-density lipoprotein-cholesterol, Lp(a)] were derived through standard procedures. RESULTS: A 10 mg/dL increase in Lp(a) was associated with 4% (95% CI, 1.01 to 1.02) higher likelihood of having ACS in younger (<45 years) and 2% (95% CI, 1.01 to 1.02) higher likelihood in middle-aged (45-60 years) individuals. Adjusting for common risk factors, elevated Lp(a), i.e. >50 mg/dL, was still associated with increased likelihood of ACS in younger adults (<45 years) (OR = 2.88, 95% CI, 1.7 to 4.6) and in middle aged ones (45 and 60 years) (OR = 2.06, 95% CI, 1.4 to 3.2), but not in older participants (>60 years) (OR = 1.31, 95% CI, 0.8 to 2.4). CONCLUSIONS: Lp(a) seems to be an independent risk factor for ACS in individuals <45 years, and high Lp(a) levels increase by ∼3folds the risk for ACS. The association is preserved but is less in middle-aged individuals (45-60 years) and is abolished >60 years.

Fluoxetine vs. placebo for the treatment of recurrent vasovagal syncope with anxiety sensitivity.

AIMS: The optimal medical therapy of patients with vasovagal syncope (VVS) remains controversial. Fluoxetine is effective against anxiety and panic disorders, while its use has shown promising results for VVS. Anxiety sensitivity is a personality trait observed in a considerable proportion of patients with VVS, associated with predisposition to anxiety and panic disorders. Our aim was to examine whether fluoxetine exerts beneficial effects regarding VVS prevention in the subset of patients with anxiety sensitivity. METHODS AND RESULTS: We assessed 106 patients with typical history of recurrent VVS, without other comorbidities, and a diagnostic, positive head-up tilt test. A psychiatric examination ruled out clinical psychiatric disease. Their psychological, stress-related profile was assessed by the Anxiety Sensitivity Index (ASI) questionnaire, a 16-item questionnaire, assessing fear of anxiety-related sensations, previously studied in VVS. Patients scoring positive for ASI (n = 60, 57% of the population) were randomized in a 2:1 fashion to receive either 10-40 mg fluoxetine daily (n = 40) or placebo (n = 20), and were followed-up for 1 year. A significant difference was observed between patients receiving fluoxetine and those with placebo, regarding the distribution of syncope-free time during the study (P < 0.05). A significant difference was also observed between the two groups regarding presyncopal events and the total number of patients who experienced syncope or presyncope during follow-up. CONCLUSION: Sensitivity to anxiety is a common personality trait in recurrent VVS. Fluoxetine is superior to placebo against syncope in these patients. This drug may be a first-line pharmacological treatment for this difficult-to-treat group.