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.

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.

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.

Background: Short-lasting (<30 s), nonsustained episodes of atrial fibrillation (NS-AF) are frequently observed in ambulatory ECG monitoring. Although they a

Objective: The 6-minute walk test is the most commonly used tool for evaluating prognosis in patients withpulmonary arterial hypertension (PAH). This study aims to identify the parameters associated with 6-minutewalk distance (6MWD) and its changes over time.Methods: Sixty-three patients diagnosed with PAH or chronic thromboembolic pulmonary hypertensionbetween January 2005 and January 2013 were included in the study. Demographic, clinical, echocardiographic, hemodynamic data, and initial and follow-up 6MWD were recorded. The 6MWD cut-off wasdetermined based on previous studies. Patients were then categorized into groups based on their initial6MWD: ≥ 332 m or < 332 m.Results: Patients were followed up for 31.56 ± 15.07 months. In those with a 6MWD < 332m, diffusingcapacity of the lungs for carbon monoxide (DLCO) (P = .040), estimated glomerular filtration rate (P = .018),and partial arterial oxygen pressure (PaO2) (P = .024) were significantly lower, whereas age (P = .016), rightatrial pressure (P = .034), the frequency of pericardial effusion (P = .004), and mortality (P = .020) weresignificantly higher. Low DLCO was identified as an independent predictor of walking less than 332 meters(P = .048). In the subgroup analysis, among idiopathic PAH (IPAH) patients, DLCO (P = .024) was lower inthose with 6MWD < 332 m. In patients with scleroderma-associated PAH (SSc-PAH), systolic pulmonaryartery pressure (sPAP) (P = .018), and mean PAP (p = 0.034) were higher in patients with 6MWD < 332 m.When the change in 6MWD (Δ6MWD) was evaluated based on the difference between the initial 6MWDand at the end of the follow-up period, DLCO was lower in the group with a decreased 6MWD (P < .001).Conclusion: The study identified higher DLCO as an independent predictor of 6MWD ≥ 332 m and itsimprovement over time. In IPAH, 6MWD is more closely associated with DLCO and PaO2, whereas in SScPAH, PAPs play a more significant role.Cite this article as: Yurtseven E, Özcan S, Karadağ B, Öngen HG, Öngen Z. Factors related to 6-minute walk distance in pulmonaryarterial hypertension. Cerrahpaşa Med J 2025, 49, 0015, doi: 10.5152/cjm.2025.25015.