Is There a Need for Sex-Tailored Lipoprotein(a) Cut-Off Values for Coronary Artery Disease Risk Stratification?

BACKGROUND: Lipoprotein(a) [Lp(a)] plasma level is a well-known risk factor for coronary artery disease (CAD). Existing data regarding the influence of sex on the Lp(a)-CAD relationship are inconsistent. OBJECTIVE: To investigate the relationship between Lp(a) and CAD in men and women and to elucidate any sex-specific differences that may exist. METHODS: Data of patients with Lp(a) measurements who were admitted to a tertiary university hospital, Koc University Hospital, were analyzed. The relationship between Lp(a) levels and CAD was explored in all patients and in subgroups created by sex. Two commonly accepted Lp(a) thresholds ≥ 30 and ≥ 50 mg/dL were analyzed. RESULTS: A total of 1858 patients (mean age 54 ± 17 years; 53.33% females) were included in the analysis. Lp(a) was an independent predictor of CAD according to the multivariate regression model for the entire cohort. In all cohort, both cut-off values (≥ 30 and ≥ 50 mg/dL) were detected as independent predictors of CAD (p < 0.001). In sex-specific analysis, an Lp(a) ≥ 30 mg/dL was an independent predictor of CAD only in women (p < 0.001), but Lp(a) ≥ 50 mg/dL was a CAD predictor both in men and women (men, p = 0.004; women, p = 0.047). CONCLUSION: The findings of this study may suggest that different thresholds of Lp(a) level can be employed for risk stratification in women compared to men.

The relationship between aerobic capacity and left atrial size in healthy young males: An observational study.

Aerobic capacity, defined as peak oxygen uptake (peakVO2), is a marker for aerobic fitness and is associated with left ventricular (LV) systolic and diastolic function. The aim of the study was to explore the relation between left atrial (LA) volume index (LAVI) and aerobic capacity in healthy young male adults. One hundred three healthy young male subjects (mean age: 34.2 ±â€…5.5years) were consecutively included in the study. All subjects underwent echocardiography to assess LAVI, LV systolic and diastolic functions. Aerobic capacity was assessed by cardiopulmonary exercise testing. All patients had normal left ventricular ejection fraction (LVEF). One hundred one subjects had normal LAVI (≤34 mL/m2) while 2 subjects had mildly increased LAVI (35-41 mL/m2). Mean peakVO2 predicted was 82.2 ±â€…14.4%. 64subjects (62.1%) had a peakVO2 < 85% of age-predicted and sex-predicted values and they had higher LAVI compared to those who had a peakVO2 higher than 85% of age-predicted and sex-predicted values (22.0 ±â€…4.8 mL/m2 vs 20.3 ±â€…4.1 mL/m2, P = .055). Notably, only LAVI showed a significant correlation with peakVO2 and predicted breathing reserve (BR), while anaerobic threshold correlated with both LAVI and LVEF. Age was also a significant factor, negatively impacting peakVO2 (r = -0.265, P = .007) and predicted BR (r = -0.282, P = .004). Multivariate analysis revealed that both LAVI and age were independent predictors of peakVO2 and predicted BR. This study suggests that LAVI can be a valuable indicator of aerobic capacity in apparently healthy young males.

Structural and Functional Impact of Adrenoceptor Beta-1 Gene Polymorphism in Patients with Hypertrophic Cardiomyopathy and Response to Beta-Blocker Therapy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetically inherited cardiac disorder with diverse clinical presentations. Adrenergic activity, primarily mediated through beta-adrenoceptors, plays a central role in the clinical course of HCM. Adrenergic stimulation increases cardiac contractility and heart rate through beta-1 adrenoceptor activation. Beta-blocker drugs are recommended as the primary treatment for symptomatic HCM patients to mitigate these effects. METHODS: This prospective study aimed to investigate the impact of common ADRB-1 gene polymorphisms, specifically serine-glycine at position 49 and arginine-glycine at position 389, on the clinical and structural aspects of HCM. Additionally, the study explored the association between these genetic variations and the response to beta-blocker therapy in HCM patients. RESULTS: A cohort of 147 HCM patients was enrolled, and comprehensive assessments were performed. The findings revealed that the Ser49Gly polymorphism significantly influenced ventricular ectopic beats, with beta-blocker therapy effectively reducing them in Ser49 homozygous patients. Moreover, natriuretic peptide levels decreased, particularly in Ser49 homozygotes, indicating improved cardiac function. Left ventricular outflow obstruction, a hallmark of HCM, was also reduced following beta-blocker treatment in all patient groups. In contrast, the Arg389Gly polymorphism did not significantly impact baseline parameters or beta-blocker response. CONCLUSION: These results emphasize the role of the Ser49Gly polymorphism in the ADRB-1 gene in shaping the clinical course and response to beta-blocker therapy in HCM patients. This insight may enable a more personalized approach to managing HCM by considering genetic factors in treatment decisions. Further research with larger populations and longer follow-up periods is needed to confirm and expand upon these findings.

The Relationship of Systolic Pulmonary Artery Pressure with Perioperative Mortality and Morbidity in Patients Undergoing Non-Cardiac Surgery: A Single-Center Experience.

OBJECTIVE: Pulmonary hypertension (PH) is associated with adverse perioperative events in patients undergoing non-cardiac surgery. In this study, we aimed to investigate the relationship between systolic pulmonary artery pressure (sPAP), evaluated by transthoracic echocardiography (TTE) before surgery, and perioperative mortality and morbidity in patients who underwent non-cardiac surgery in our center. METHODS: Of the 3425 retrospectively screened patients who underwent non-cardiac surgery, 3049 patients whose estimated sPAP values were previously determined by TTE were included in the study. Patients were classified into 3 groups according to their estimated sPAP levels. sPAP <35 mmHg formed group 1, 35-39 mmHg group 2, and ≥ 40 mmHg group 3. All demographic and perioperative data obtained from the database of our institute were compared in three groups. RESULTS: Of the 3049 patients enrolled in the study, 2406 (78.9%) were in group 1, 259 (8.5%) in group 2, and 384 (12.6%) in group 3. Thirty-day all-cause mortality was observed in 82 (2.7%) patients, cardiac mortality occurred in 9 patients (0.3%). In the group with sPAP ≥40 mmHg, cardiac mortality was 0.5% and all-cause mortality was 7.3%. Thirty-day all-cause mortality, acute pulmonary edema, and acute renal failure were significantly higher in group 3 than in the other groups. Cardiac mortality did not differ significantly between the groups. Age, sPAP value, and chronic obstructive pulmonary disease history were revealed as independent predictors of all-cause mortality in multivariate logistic regression analysis. CONCLUSION: In conclusion, increased sPAP is associated with adverse postoperative outcomes. The evaluation of sPAP with TTE before non-cardiac surgery in patients whose clinical features and examination findings suggest PH may contribute to preoperative risk assessment.

Echocardiographic assessment of left ventricular filling pressure in patients with acute ST elevation myocardial infarction: an invasive validation study.

Backgrounds Assessment of left ventricular filling pressure (LVFP) is of clinical importance in patients with ST elevation myocardial infarction (STEMI). Although several echocardiographic parameters are recommended for the assessment of LVFP, validation of these parameters in patients with STEMI is missing. We aimed to investigate the clinical utility of these parameters in acute settings. Methods: We prospectively included consecutive patients with STEMI. LV end-diastolic pressure (LVEDP) was measured following primary PCI and echocardiographic examination was performed within 24 hours. Mean left atrial pressure (mLAP) was calculated both invasively using Yamamoto's formula and non-invasively using Naugeh's formula. Mean LAP was considered increased when exceeded 18 mmHg. Results: Patients were grouped according to LVEDP, group 1(41 patients) and group 2(114 patients).There was no significant difference between groups in terms of comorbidities. NT pro-BNP levels (p < 0.001) and peak level of Hs-TnT (p-value: 0.002) were significantly higher in group 2. Average E/e' ratio was significantly higher in group 2 (10.19 ± 3.15 vs. 12.04 ± 4.83, p: 0.046). Isovolumetric relaxation time was longer in group 2 (p < 0.001) and left atrial volume index (LAVI) was also significantly higher in group 2 (p < 0.001). Regression analyses revealed that septal, lateral and average E/e' ratio, tricuspid regurgitation velocity, LAVI and left ventricular volume are correlated with mLAP. Among group 2 patients only 14 Patients fulfilled the increased LVFP criteria suggested by current guidelines. Conclusions Echocardiographic parameters indicating increased LVFP require validation and may need to be modified in patients with STEMI. Moreover, current algorithms underestimate the actual number of patients with increased LVFP.

An Update on the Role of PCSK9 in Atherosclerosis.

Atherosclerosis is initiated by functional changes in the endothelium accompanied by accumulation, oxidation, and glycation of LDL-cholesterol in the inner layer of the arterial wall and continues with the expression of adhesion molecules and release of chemoattractants. PCSK9 is a proprotein convertase that increases circulating LDL levels by directing hepatic LDL receptors into lysosomes for degradation. The effects of PCSK9 on hepatic LDL receptors and contribution to atherosclerosis via the induction of hyperlipidemia are well defined. Monoclonal PCSK9 antibodies that block the effects of PCSK9 on LDL receptors demonstrated beneficial results in cardiovascular outcome trials. In recent years, extrahepatic functions of PCSK9, particularly its direct effects on atherosclerotic plaques have received increasing attention. Experimental trials have revealed that PCSK9 plays a significant role in every step of atherosclerotic plaque formation. It contributes to foam cell formation by increasing the uptake of LDL by macrophages via scavenger receptors and inhibiting cholesterol efflux from macrophages. It induces the expression of inflammatory cytokines, adhesion molecules, and chemoattractants, thereby increasing monocyte recruitment, inflammatory cell adhesion, and inflammation at the atherosclerotic vascular wall. Moreover, low shear stress is associated with increased PCSK9 expression. PCSK9 may induce endothelial cell apoptosis and autophagy and stimulate the differentiation of smooth muscle cells from the contractile phenotype to synthetic phenotype. Increasing evidence indicates that PCSK9 is a molecular target in the development of novel approaches toward the prevention and treatment of atherosclerosis. This review focuses on the molecular roles of PCSK9 in atherosclerotic plaque formation.

The clinical significance of premature atrial contractions: How frequent should they become predictive of new-onset atrial fibrillation.

BACKGROUND: Although previous studies reported frequent premature atrial contractions(fPACs) increased the risk of adverse cardiovascular outcomes, especially atrial fibrillation(AF), there is a substantial inconsistency between reports concerning the definition of fPAC. In this study, we aimed to investigate the relationship between fPAC and cardiovascular outcomes, especially AF. We further searched for a cutoff value of fPAC for prediction of AF. METHODS: We retrospectively analyzed the ambulatory 24-hr Holter monitoring records and 392 patients included. Frequent PAC was defined as more than 720 PAC/24 hr as used for frequent ventricular premature beats. Patients' baseline characteristics, echocardiographic variables and medical history were recorded. RESULTS: There were 189 patients with fPAC and 203 patients without fPAC. Patients with fPAC had more comorbidities in terms of hypertension, diabetes mellitus, coronary artery disease and congestive heart failure. CHA2DS2-VaSc was higher in patients with fPAC. Mean follow-up duration was 31 months, and the number of patients with new-onset AF during follow-up was significantly higher in fPAC group (22% vs. 5%, p < .001). fPAC was significantly and independently associated with new-onset AF and predicted AF with a cutoff value of 3,459 PAC/24 hr, and the risk of AF was 11-fold higher than those with <3,000 PAC/24 hr. In addition, an increased CHA2DS2-VaSc score was also associated with new-onset atrial fibrillation. CONCLUSION: In our study, we have demonstrated that fPAC is significantly associated with new-onset AF, and this association is the strongest among those patients who have more than 3,000 PAC in 24 hr.

Prognostic significance of brain-derived neurotrophic factor levels in patients with heart failure and reduced left ventricular ejection fraction.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. The aim of the present study was to investigate the relationship between BDNF levels and prognostic markers in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF), considering death or rehospitalization due to HF. METHODS: Patients with severe left ventricular systolic dysfunction (LVEF ≤35%) and individuals with no history of cardiac disease (control group) were included in the study conducted between 2013 and 2017. Of the included patients, 52 were classified as mildly symptomatic [New York Heart Association (NYHA) I-II], and 108 were classified as severely symptomatic (NYHA III). The control group comprised 50 individuals. The primary endpoints of the study consisted of cardiovascular death during long-term follow-up and hospitalization for worsening of HF. RESULTS: The mean age of the patient group was 67.60±11.45 years and 58% were male, whereas that of the control group was 66.28±11.30 years and 48% were male. The N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) serum levels in patients with HF were higher, whereas the BDNF values were lower than those in the control group (NT-pro-BNP: 5010±851 pg/mL vs. 33±11 pg/mL, p<0.001; BDNF: 8.64±1.12 ng/mL vs. 17.58±4.51 ng/mL, p<0.001). Multivariable analysis suggested that there was a significant association between BDNF levels and clinical status, generating the primary endpoints of death [BDNF levels: Odds ratio (OR)=0.17, 95% confidence interval (CI): 0.05-0.53, p=0.002], and rehospitalization (BDNF levels: OR=0.702, 95% CI: 0.54-0.92, p=0.010). CONCLUSION: Decreased serum BDNF levels were associated with death and rehospitalization in patients with HF, suggesting that these levels can be useful prognostic biomarkers.

The quality of ECG data acquisition, and diagnostic performance of a novel adhesive patch for ambulatory cardiac rhythm monitoring in arrhythmia detection.

BACKGROUND: Short and long ambulatory electrocardiographic monitoring with different systems is a widely used method to detect cardiac arrhythmias. In this study, we aimed to evaluate the effectiveness of a novel monitoring device on cardiac arrhythmia detection. METHODS: We used two different protocols to evaluate device performance. For the first one, 36 healthy subjects were enrolled. The standard 12­lead, 24-h Holter monitoring and the novel single lead electrocardiogram (ECG) Patch Monitor (EPM) device (BeyondCare®, Rooti Labs Ltd., Taipei, Taiwan) were simultaneously applied to all subjects for 24 h. The quality of ECG data acquisition of novel system was compared to that of standard Holter. The second phase included 73 patients that were referred from our outpatient arrhythmia clinic for evaluation of their symptoms relevant to the cardiac arrhythmias. Advanced algorithms, statistical methods (cross-correlation method, Pearson's correlation coefficient, Bland-Altman plots) were used to process and verify the acquired data. RESULTS: The overall average beat per minute correlation between BeyondCare® and standard 12­lead Holter was found 98% in 33 healthy subjects. The mean percentage of invalid measurements in BeyondCare® was 1.6% while the Holter's was 1.7%. In the second protocol of the study, prospective data from 67 patients who were referred for evaluation of their symptoms relevant to cardiac arrhythmias, showed that the mean BeyondCare® wear time was 4.7 ±â€¯0.5 days out of five total days per protocol. The mean analyzable wear time was 93.6%. The water-resistant design enabled 73.5% of the participants to take a shower. 7.3% of participants had minor skin irritations related to the electrodes. Among the patients with detected arrhythmia (40.2% of all patients), 29.6% had their first arrhythmia after the initial two days period. A clinically significant pause was detected in one patient, ventricular tachycardia was detected in four patients, and supraventricular tachycardia was detected in 15 patients. Paroxysmal atrial fibrillation was identified in seven patients. Three of them had their first episodes after the second day of monitoring. CONCLUSION: BeyondCare® Patch was well-tolerated and allowed prolonged time periods for continuous ECG monitoring, may result in an improvement in clinical accuracy and detection of arrhythmias by cloud-based artificial intelligence operating system.

The prognostic significance of narrow fragmented QRS on admission electrocardiogram in patients hospitalized for decompensated systolic heart failure.

BACKGROUND: Narrow fragmented QRS (fQRS) has recently been recognized as a significant predictor of prognosis in various cardiovascular diseases. HYPOTHESIS: We hypothesized that the presence of narrow fQRS on admission electrocardiogram (ECG) in patients with decompensated systolic heart failure (HF) of any cause would be associated with long-term prognosis. METHODS: Patients hospitalized for decompensated HF due to ischemic or nonischemic dilated cardiomyopathy (left ventricular ejection fraction <35%) were retrospectively analyzed. The primary clinical end points were cardiovascular mortality, sudden cardiac death, and rehospitalization for HF. RESULTS: The mean duration of follow-up was 3.73 ± 1.41 years. Patients were classified as fQRS(+) group (n = 114; mean age, 63.49 ± 12.04 years) and fQRS(-) group (n = 113 patients; mean age, 65.04 ± 11.95 years). fQRS on ECG was significantly correlated with New York Heart Association (NYHA) functional class (P = 0.001). In multivariate Cox proportional hazard analysis, narrow fQRS (odds ratio [OR]: 3.130, 95% confidence interval [CI]: 1.560-2.848, P = 0.001), chronic renal failure (OR: 2.455, 95% CI: 1.120-5.381, P = 0.025), NYHA class (OR: 8.305, 95% CI: 2.568-26.855, P < 0.0001), and hypoalbuminemia (OR: 2.099, 95% CI: 1.122-3.926, P = 0.020) were independent predictors of cardiovascular mortality. In Kaplan-Meier survival analysis, narrow fQRS on admission ECG predicted worse survival rate at 84 months; survival probability significantly decreased in the fQRS(+) group compared with fQRS(-) group (P < 0.0001). CONCLUSIONS: Presence of narrow fQRS is associated with worse NYHA functional class in patients hospitalized for decompensated HF. Narrow fQRS predicts cardiovascular mortality in a specific subgroup of systolic HF patients, namely those hospitalized for decompensated HF of both ischemic and nonischemic causes.