Tolga Kunak

Amaç: Pan-immün-inflamasyon değeri (PIV), kardiyovasküler hastalıklarda araştırılan bileşik bir inflamatuvar biyobelirteçtir. Bu çalışmada, karotis arter stentleme (KAS) uygulanan hastalarda PIV ile vasküler komorbidite yükü arasındaki ilişkinin araştırılması amaçlandı. Gereç ve Yöntemler: Retrospektif çalışmaya 2010–2025 yılları arasında KAS uygulanan 221 hasta dahil edildi. PIV periferik kan hücrelerinden hesaplandı. Vasküler yük skoru; hipertansiyon, diabetes mellitus, hiperlipidemi, sigara, koroner arter hastalığı ve geçirilmiş serebrovasküler olaydan oluşan altı bileşenle belirlendi. Hastalar düşük (0–2) ve yüksek (3–5) yük gruplarına ayrıldı. İlişkiler korelasyon ve regresyon analizleriyle, ayırt edici performans ROC analiziyle değerlendirildi. Bulgular: PIV, yüksek vasküler yük grubunda daha yüksekti (428,9 [287,1–701,9] vs. 287,1 [202,1–452,5], p=0,001). PIV ile vasküler yük arasında pozitif korelasyon vardı (rho=0,317, p<0,001). Her 100 birimlik PIV artışı, yüksek vasküler yük ile bağımsız ilişkiliydi (OR=1,152; %95 GA: 1,058–1,255; p=0,001). Düzeltilmiş ordinal regresyonda PIV, daha yüksek vasküler yük ile ilişkiliydi (OR=1,116; %95 GA: 1,062–1,174; p<0,001). ROC analizinde AUC 0,651 (%95 GA: 0,577–0,725) bulundu. Sonuç: Yüksek PIV, KAS hastalarında daha yüksek vasküler komorbidite yükü ile bağımsız ilişkilidir. Ancak sınırlı ayırt edici performansı nedeniyle PIV tek başına risk sınıflandırma aracı olarak kullanılmamalıdır.

Background and Objectives: Lipoprotein(a) [Lp(a)] is an established cardiovascular risk factor associated with atherosclerosis, vascular inflammation, and endothelial dysfunction. However, data regarding its relationship with hypertension-mediated organ damage and circadian blood pressure abnormalities remain limited. We aimed to investigate the association of elevated Lp(a) levels with carotid atherosclerosis and nocturnal blood pressure dipping patterns in patients with hypertension. Materials and Methods: This retrospective cross-sectional study included 80 nondiabetic patients with essential hypertension. Patients were categorized according to serum Lp(a) levels into elevated Lp(a) (≥50 mg/dL, n = 20) and lower Lp(a) (n = 60) groups. All participants underwent carotid ultrasonography, transthoracic echocardiography, ambulatory blood pressure monitoring, and ophthalmologic evaluation. Multivariable logistic and linear regression analyses were performed to determine independent associations between Lp(a), carotid plaque presence, and nocturnal dipping percentage. Results: Patients with elevated Lp(a) levels had a significantly higher prevalence of carotid plaque (55.0% vs. 23.3%, p = 0.008) and non-dipper hypertension (75.0% vs. 46.7%, p = 0.028) compared with patients with lower Lp(a) levels. Serum Lp(a) concentrations were inversely correlated with nocturnal dipping percentage (r = −0.362, p = 0.001). In multivariable logistic regression analysis adjusted for age, sex, LDL cholesterol, and active smoking, elevated Lp(a) remained independently associated with carotid plaque presence (OR 3.24, 95% CI 1.06–9.80, p = 0.039). In multiple linear regression analysis adjusted for age, sex, LDL cholesterol, and office systolic blood pressure, higher Lp(a) levels remained independently associated with lower nocturnal dipping percentage (β = −0.294, p = 0.008). No significant associations were observed between Lp(a) and carotid intima–media thickness, left ventricular hypertrophy, hypertensive retinopathy, or renal functional parameters. Conclusions: Elevated Lp(a) levels were independently associated with carotid plaque presence and impaired nocturnal blood pressure decline in hypertensive patients. These findings suggest that Lp(a) may be more closely linked to focal macrovascular atherosclerosis and abnormal circadian blood pressure regulation rather than diffuse hypertensive structural remodeling.

Background: Benidipine is a long-acting calcium channel blocker used for the treatment of hypertension and chronic coronary syndrome. Although it effectively lowers blood pressure (BP), the relationship between BP reduction and improvement in angina-related health status during benidipine therapy remains uncertain. This study evaluated changes in BP and patient-reported angina-related health status in a large real-world cohort. Methods: This prospective, multicenter, observational cohort study included 1659 patients with hypertension and/or chronic coronary syndrome who underwent baseline clinical assessment before initiation of benidipine therapy and were reassessed after 3 months. Changes in systolic and diastolic BP and Seattle Angina Questionnaire-7 (SAQ-7) scores were evaluated. Multivariable linear regression analyses were performed to identify predictors of BP reduction and symptomatic improvement. A propensity score-matched analysis according to coronary artery disease (CAD) status was conducted to further explore differences in treatment response. Results: The mean age was 62.2 ± 12.2 years, and 54.0% of participants were women. Systolic BP decreased by 13.8 mmHg and diastolic BP by 6.7 mmHg (both p < 0.001). Mean SAQ-7 score increased by 8.1 points (p < 0.001), exceeding the established threshold for clinically meaningful improvement. Baseline SAQ-7 score showed the strongest association with change in SAQ-7, whereas baseline systolic BP was the strongest predictor of BP reduction. The correlation between changes in systolic BP and SAQ-7 was weak (r = 0.058, p = 0.023). In the propensity score-matched cohort (n = 732), BP reduction was similar regardless of CAD status, whereas improvement in SAQ-7 was greater in patients without obstructive CAD. Conclusions: In this multicenter real-world cohort, benidipine therapy was associated with significant BP reduction and clinically meaningful improvement in angina-related health status over 3 months. Symptomatic improvement showed only a weak association with BP reduction. These findings should be interpreted within the limitations of an observational study and warrant confirmation in controlled comparative studies.

Insulin resistance and metabolic dysregulation are increasingly recognized as contributors to myocardial remodeling and phenotypic heterogeneity in hypertrophic cardiomyopathy (HCM). While the triglyceride-glucose (TyG) index offers a simple surrogate marker of insulin resistance, its relationship with left ventricular outflow tract (LVOT) obstruction in HCM patients remains underexplored. This study aimed to investigate the association between the TyG index and LVOT obstruction in a retrospective observational cohort of 124 adult HCM patients. LVOT obstruction was defined as a resting or provoked gradient of ≥30 mmHg. Clinical, laboratory, and echocardiographic data were systematically evaluated. The TyG index was computed from fasting triglyceride and glucose levels. Multivariable logistic regression analysis, with the TyG index scaled per 0.1-unit increment, was used to assess independent associations. Receiver operating characteristic (ROC) curve analysis determined discriminatory performance. Patients with obstructive HCM exhibited significantly higher TyG index values compared to those without obstruction (9.07 ± 0.25 vs. 8.76 ± 0.21, p<0.001). The TyG index maintained an independent association with LVOT obstruction after adjusting for relevant clinical and echocardiographic covariates (per 0.1-unit increase: OR 1.84, 95% CI 1.40–2.42, p<0.001). Furthermore, the TyG index demonstrated moderate correlations with both resting (r=0.519, p<0.001) and provoked (r=0.557, p<001) LVOT gradients. ROC analysis indicated good discriminatory performance (AUC: 0.826, 95% CI: 0.752–0.901), with a cut-off value of 8.75 yielding 87.9% sensitivity and 47.0% specificity. In conclusion, the TyG index was independently associated with LVOT obstruction in HCM patients, with higher values observed in those with the obstructive phenotype. This suggests a potential link between metabolic status and disease manifestation in HCM. Given its cost-effectiveness and accessibility, the TyG index may offer valuable complementary clinical insights. However, this association requires cautious interpretation, and prospective studies are essential to establish its clinical and prognostic utility.

Background: Non-organic ED patients have cardiac autonomic dysfunction measurable by heart rate variability (HRV). Tadalafil reduces cardiovascular mortality, but exact mechanisms remain unclear. Aim: To evaluate daily tadalafil effects on cardiac autonomic regulation in non-organic ED and identify clinical predictors of HRV response. Methods: In this prospective study, 82 men with non-organic ED (mean age 46.8 ± 5.0 years) received tadalafil 5-10 mg daily. Assessment included International Index of Erectile Function-Erectile Function (IIEF-EF), echocardiography, laboratory tests, and 24-hour Holter ECG. HRV was analyzed via time-domain (standard deviation of NN intervals [SDNN], root mean square of successive differences [RMSSD]) and frequency-domain (low-frequency power [LF], high-frequency power [HF], LF/HF ratio) parameters. Post-treatment recordings were blindly evaluated. Early response to tadalafil was defined as achievement in the severity-adjusted Minimal Clinically Important Difference (MCID) in IIEF-EF or final IIEF-EF score ≥26. Outcomes: Primary: ΔSDNN. Secondary: ΔHF power, ΔLF/HF ratio. Results: IIEF-EF improved significantly (15 to 23, P < .001) and 74.4% were early responders (n = 61). In the overall cohort, SDNN increased (42.39 to 52.39 ms, P < .01), HF power increased (267.86 to 294.44 ms2,P < .001), and LF/HF ratio decreased (2.78 to 2.31, P < .01). Both groups showed HRV improvements without between-group differences (P > .05), suggesting autonomic modulation independent of erectile response. Multivariable regression: diabetes negatively predicted SDNN improvement; higher testosterone, higher baseline IIEF-EF score, and lower BMI predicted greater HF enhancement. Only 1.1% of patients discontinued the treatment (due to dyspepsia). Clinical Implications: Daily tadalafil treatment may enhance parasympathetic modulation in men with non-organic ED regardless of clinical erectile improvement, suggesting a potential mechanism for its observed cardiovascular benefits. Strengths and Limitations: Strengths include rigorous, blinded Holter assessment. Limitations include the lack of a placebo control, short follow-up (28 days), and a small non-responder subgroup. Conclusion: Daily tadalafil enhanced parasympathetic modulation and reduced sympathovagal imbalance independently of erectile improvement.

Background: Achieving target low-density lipoprotein cholesterol (LDL-C) levels in patients with atherosclerotic cardiovascular disease (ASCVD) frequently requires combination lipid-lowering therapy. Single-pill combination (SPC) regimens may improve adherence compared with free-dose combinations (FDC) in real-world clinical practice. Methods: This retrospective observational study included 450 ASCVD patients with baseline LDL-C levels of 70–189 mg/dL who were followed in cardiology outpatient clinics between January 2023 and December 2024. Patients received atorvastatin–ezetimibe either as a single-pill combination (SPC, n = 392) or as a free-dose combination (FDC, n = 58). Primary endpoints were LDL-C reduction and treatment adherence (≥ 80% of prescribed doses). Secondary endpoints included LDL-C target attainment and adverse events. Non-parametric tests and chi-square/Fisher’s exact tests were used for statistical analysis. Results: At 1 month, LDL-C levels were significantly lower in the SPC group compared with the FDC group (90.6 vs. 119 mg/dL; p = 0.005), and adherence was higher (89.8% vs. 70.7%; p < 0.001). At 4 months, LDL-C levels were comparable between groups, while continuous adherence remained significantly higher in the SPC group (86% vs. 69%; p = 0.001). A higher proportion of SPC-treated patients achieved LDL-C < 100 mg/dL at 1 month (81.9% vs. 67.2%; p = 0.009). Conclusions: In this real-world ASCVD cohort, SPC therapy with atorvastatin and ezetimibe was associated with superior adherence and comparable lipid-lowering efficacy despite lower statin doses. Fixed-dose combination strategies may represent an effective approach to optimize adherence and cardiovascular risk management.

Background: Right ventricular (RV) dysfunction in chronic kidney disease (CKD) remains underrecognized. The tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio (TAPSE/sPAP) reflects RV‐pulmonary arterial coupling, but its relationship with CKD severity is unknown. To evaluate the association between TAPSE/sPAP ratio and CKD stage severity and assess age‐related effect modification. Methods: This cross‐sectional study enrolled 120 participants: 40 patients with stage I–II CKD, 40 with stage III–IV CKD, and 40 healthy controls. All underwent echocardiography and nephrologist evaluation. Proportional odds regression models adjusted for cardiovascular risk factors evaluated the TAPSE/sPAP‐CKD association. ROC analysis assessed discriminatory performance. Age‐stratified analyses (p  < 0.01). Each 0.10‐unit decrease was independently associated with advanced CKD (adjusted OR 2.08, 95% CI 1.49–2.89, p < 0.001). TAPSE/sPAP ratio achieved the highest AUC (0.734, 95% CI 0.625–0.833), outperforming TAPSE alone (AUC 0.615; DeLong p  = 0.049), while statistically comparable to sPAP (AUC 0.715; DeLong p  = 0.400). Age‐stratified analysis revealed excellent performance in patients p  = 0.015). Random forest analysis identified age (35.8%) and TAPSE/sPAP (22.0%) as dominant predictors. Conclusions: TAPSE/sPAP ratio is an independent marker of CKD severity enabling non‐invasive detection of RV‐PA uncoupling, with excellent discriminatory performance in younger but limited utility in older patients, suggesting that age‐specific interpretation and integration with renal biomarkers are recommended.

Objective: Early-onset paroxysmal atrial fibrillation (PAF) in individuals without conventional cardiovascular risk factors has traditionally been labeled as “lone AF.” Recent evidence suggests that subtle structural, electrical, and functional abnormalities may still exist. This study evaluated atrial conduction, diastolic function, endothelial function, and systemic inflammation in early-onset PAF patients without structural heart disease or overt comorbidities. Methods: In this cross-sectional study, 40 patients aged 18–65 years with documented early-onset PAF were compared with 40 age and sex matched healthy individuals in sinus rhythm. All subjects underwent measurement of P wave dispersion and signal-averaged P wave duration, echocardiographic assessment of diastolic parameters, evaluation of endothelial function using flow-mediated dilation (FMD), and analysis of systemic inflammation via high-sensitivity C-reactive protein (hsCRP). Results: Patients with PAF demonstrated significantly increased P wave dispersion (51.63 ± 11.17 ms vs. 35.13 ± 6.15 ms; p < 0.001) and prolonged signal-averaged P wave duration (146.75 ± 19.68 ms vs. 124.40 ± 9.05 ms; p < 0.001). Diastolic dysfunction was evident, characterized by a reduced E/A ratio and elevated septal E/E′. Left atrial volume index was significantly higher in the PAF group (29.79 ± 3.94 mL/m² vs. 28.23 ± 1.74 mL/m²; p = 0.025). Endothelial function was impaired, as reflected by lower FMD values (5.27 ± 1.94% vs. 6.65 ± 1.78%; p = 0.001), while hsCRP levels were significantly higher in the PAF group (0.40 [0.30–0.55] vs. 0.24 [0.20–0.30] mg/dL; p < 0.001). Multivariate analysis identified signal-averaged P wave duration, P wave dispersion, mitral E wave velocity, septal E/E′, and left atrial volume index as independent predictors of PAF. Conclusion: Even in the absence of overt cardiovascular disease, early-onset PAF is associated with meaningful disturbances in atrial conduction, diastolic performance, endothelial function, and systemic inflammation. These findings support the presence of early atrial cardiomyopathy and underscore the need for comprehensive cardiovascular evaluation in younger PAF patients.

ObjectiveThe Fibrosis-4 (FIB-4) index is a simple, non-invasive marker originally developed to estimate hepatic fibrosis and has recently emerged as a potential indicator of systemic inflammation and atherosclerosis. This study investigated the association between the preprocedural FIB-4 index and previous cerebrovascular events in patients undergoing carotid artery stenting (CAS).Materials and MethodsThis retrospective observational study included 221 consecutive patients who underwent CAS for significant carotid artery stenosis. Patients were categorized according to the presence or absence of previous cerebrovascular events. Demographic, clinical, and laboratory characteristics were compared between groups. Multivariable logistic regression analysis was performed to identify independent predictors of previous cerebrovascular events. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminative ability of the FIB-4 index, and the optimal cut-off value was determined using the Youden index, based on the best balance between sensitivity and specificity.ResultsAmong the 221 patients, 133 (60.2%) had a history of previous cerebrovascular events. Compared with patients without previous cerebrovascular events, those with previous cerebrovascular events had significantly lower platelet counts and HDL cholesterol levels and significantly higher fasting glucose and FIB-4 index values (all p < 0.05). In multivariable logistic regression analysis, chronic kidney disease (OR: 3.06, 95% CI: 1.46–6.39, p = 0.003), lower HDL cholesterol (OR: 0.96 per 1 mg/dL increase, 95% CI: 0.93–0.99, p = 0.011), and a higher FIB-4 index (OR: 2.19 per 1-unit increase 95% CI: 1.29–3.73, p = 0.004) were independently associated with previous cerebrovascular events. ROC analysis demonstrated modest discriminatory performance of the FIB-4 index (AUC: 0.611, 95% CI: 0.535–0.687, p = 0.005). A FIB-4 value of 1.54 yielded a sensitivity of 51.1% and a specificity of 64.8% for identifying patients with previous cerebrovascular events.ConclusionAn elevated preprocedural FIB-4 index was independently associated with previous cerebrovascular events in patients undergoing carotid artery stenting. Although its discriminatory performance was modest, the FIB-4 index may serve as an inexpensive and readily available biomarker that may provide complementary information regarding systemic vascular risk. Larger prospective multicenter studies are warranted to validate this association and determine the potential clinical utility of FIB-4 in this population.