Associations between Various Inflammatory Markers and Carotid Findings in a Voluntary Asymptomatic Population Sample.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.

Acute pulmonary embolism pretest probability estimation by d-dimer test, our modified, new ECG score and clinical prediction rules.

Objectives: We investigated whether a sufficiently sensitive D-dimer test could exclude acute pulmonary embolism (acPE) as a stand-alone diagnostic test and compared our previously published, modified ECG score with the Wells and Geneva scores in the estimation of acPE pretest probability. Methods: We retrospectively evaluated 345 patients who underwent chest CT angiography (CTA) for the suspicion of acPE. The pretest probability of acPE was assessed in 120 D-dimer negative [DD (-)] and 225 D-dimer positive [DD (+)] patients. Results: Chest CTA verified acPE in 57/345 (16.5 %) patients and in 1/120 (0.8 %) DD (-) patient. In DD (-) patients the test accuracy (TA) and specificity (SP) of the ECG score (98 %, 99 %) were better than those of the Wells score (92.5 %, 92.4 %) (p = 0.063 and p < 0.05 respectively) and the Geneva score (76.7 %, 76.5 %) (p < 0.001 for both), the Wells score TA and SP were greater than those of the Geneva score (p < 0.001 for both). In DD (+) patients the SPs, TAs and positive predictive values (PPV) of the ECG score (94 %, 78.6 %, 69 %) and the Wells score (91.8 %, 75.1 %, 48 %) were greater than those of the Geneva score (71.3 %, 64.9 %, 38.2 %) (p < 0.001 for both SP and TA respectively, and p < 0.001 for PPV of the ECG score vs. the Geneva score and p < 0.05 for PPV of the Wells score vs. Geneva score), their sensitivities (SE) (36.4 %, 23.6 %) were less than that of the Geneva score (47.5 %) (p < 0.05 and p < 0.001 respectively). The ECG score's TA in a trend, its SE and PPV were significantly (p < 0.01 and p < 0.001) better than those of the Wells score. Conclusion: In contrast to the current guidelines, a stand-alone high sensitivity DD (-) test, without prediction rules, could reliably exclude acPE. Our ECG score slightly outperformed the Wells score, the ECG score and Wells score far outperformed the Geneva score in the estimation of acPE pretest probability. An acPE diagnosis with the ECG score, in addition to the supportive diagnosis with the clinical prediction rules, may further increase the chance of true DD positivity.

Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease.

Age-related disorders are closely linked to the accumulation of senescent cells. The senescence-associated secretory phenotype (SASP) sustains and progresses chronic inflammation, which is involved in cellular and tissue dysfunction. SASP-related growth and differentiation factor-15 (GDF-15) is an immunoregulatory cytokine that is coupled to aging and thus may have a regulatory role in the development and maintenance of atherosclerosis, a major cause of cardiovascular disease (CVD). Although the effects of GDF-15 are tissue-specific and dependent on microenvironmental changes such as inflammation, available data suggest that GDF-15 has a significant role in CVD. Thus, GDF-15 is a promising biomarker and potential therapeutic target for atherosclerotic CVD.

Association of growth and differentiation factor-15 with coronary artery calcium score and ankle-brachial index in a middle-aged and elderly Caucasian population sample free of manifest cardiovascular disease.

Growth and differentiation factor-15 (GDF-15) is a stress-associated cytokine of the transforming growth factor-ß superfamily. The inflammatory and angiogenic effects of GDF-15 in atherosclerosis are controversial, and its correlation with the long asymptomatic phase of the disease is not well understood. Coronary artery calcium score (CACS) and ankle-brachial index (ABI) are sensitive markers of subclinical atherosclerosis. To date, only a few studies have examined the impact of GDF-15 on coronary artery calcification, and the association between GDF-15 and ABI has not been evaluated. Therefore, we aimed to investigate the possible relationship between serum GDF-15 concentrations and CACS and ABI in a Caucasian population sample of middle-aged (35-65 years) and elderly (> 65 years) people. In addition to recording demographic and anthropometric characteristics, atherosclerotic risk factors, and laboratory tests including serum HDL-cholesterol, LDL-cholesterol, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP); GDF-15 level, cardiac computed tomography, and ABI measurements were also performed. A total of 269 asymptomatic individuals (men, n = 125; median age, 61.5 [IQR, 12.7] years) formed the basis of this study. Participants were divided into two groups according to their age (middle-aged, n = 175 and elderly, n = 94). Hypertension and diabetes mellitus were significantly more prevalent and CACS values and HbA1c, NT-proBNP, and GDF-15 levels were significantly higher (all p < 0.001) in the elderly group compared to the middle-aged group. Multivariate ridge regression analysis revealed a significant positive association between GDF-15 and CACS (middle-aged group: ß = 0.072, p = 0.333; elderly group: ß = 0.148, p = 0.003), and between GDF-15 and ABI (middle-aged group: ß = 0.062, p = 0.393; elderly group: ß = 0.088, p = 0.041) only in the elderly group. Our results show that GDF-15 is not only a useful biomarker of inflammation but can also predict early signs of asymptomatic atherosclerosis, especially in elderly people with chronic systemic inflammation associated with aging (inflammaging).

Useful Electrocardiographic Signs to Support the Prediction of Favorable Response to Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a cornerstone therapeutic opportunity for selected patients with heart failure. For optimal patient selection, no other method has been proven to be more effective than the 12-lead ECG, and hence ECG characteristics are extensively researched. The evaluation of particular ECG signs before the implantation may improve selection and, consequently, clinical outcomes. The definition of a true left bundle branch block (LBBB) seems to be the best starting point with which to select patients for CRT. Although there are no universally accepted definitions of LBBB, using the classical LBBB criteria, some ECG parameters are associated with CRT response. In patients with non-true LBBB or non-LBBB, further ECG predictors of response and non-response could be analyzed, such as QRS fractionation, signs of residual left bundle branch conduction, S-waves in V6, intrinsicoid deflection, or non-invasive estimates of Q-LV which are described in newer publications. The most important and recent study results of the topic are summarized and discussed in this current review.

Serum Uric Acid Is Independently Associated with Coronary Calcification in an Asymptomatic Population.

Detecting early-stage atherosclerosis is an important step towards cardiovascular disease prevention. Coronary artery calcium (CAC) score is a sensitive and non-invasive tool for detecting coronary atherosclerosis. Higher serum uric acid (SUA) levels are known to be associated with cardiovascular diseases. However, there is inconsistency regarding the independence of the association. The aim of our study was to assess the association of CAC and SUA in an asymptomatic population. CAC scans of 281 participants were analyzed in a voluntary screening program. A health questionnaire, physical examination, and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. 36.3% (n = 102) of the participants had no detectable CAC and 13.9% (n = 39) had a CAC score of > 300. SUA showed positive correlation with CAC score (0.175, p < 0.01). SUA was independently associated with Ca score > 300 (OR 5.17, p = 0.01) after the effects of conventional risk factors were eliminated.

Signs of subclinical atherosclerosis in asymptomatic patients at increased risk of type 2 diabetes mellitus.

AIMS: We aimed to study carotid intima media thickness (CIMT) in asymptomatic patients with an increased risk of type 2 diabetes mellitus (T2DM) and in a pre-diabetic state. METHODS: Diabetes risk assessment was performed in 2420 participants in a voluntary screening program between 2011 and 2013. The risk of T2DM was estimated by the Findrisc scoring system (FR). A FR≥12 was considered as increased risk. HbA1c% between 5.7 and 6.4% signified a pre-diabetic state. Carotid duplex scan was performed and CIMT above 0.9 mm was regarded as pathological. Patients with T2DM or a history of cardiovascular disease were excluded. RESULTS: Overall 1475 subjects were included. Four groups were compared: "control" (normal HbA1c, FR<12), "HbA1c only" (HbA1c: 5.7-6.4%, FR<12), "Findrisc only" (normal HbA1c, FR≥12) and "combined" (HbA1c: 5.7-6.4%, FR≥12). Frequency of pathological maximal CIMT was 9.4%, 19.7%, 27.4% and 36.4% in the groups, respectively (p<0.001). Logistic regression analysis revealed that compared to control subjects, sex and risk factor-adjusted Odds Ratios for the presence of pathological maximal CIMT were 2.2 (p<0.001), 3.4 (p<0.001) and 5.1 (p<0.001) for the groups, respectively. CONCLUSIONS: Evaluation of Findrisc score and HbA1c at population level may facilitate early recognition of subclinical vascular complications even in the pre-diabetic state.