Cardiovascular Biomarkers and Calculated Cardiovascular Risk in Orally Treated Type 2 Diabetes Patients: Is There a Link?

The aim of the study was to test the correlation of serum levels of asymmetric dimethylarginine (ADMA), endothelin 1 (ET-1), N-terminal brain natriuretic pro-peptide (NT-proBNP), and placental growth factor (PIGF-1) with estimated cardiovascular (CV) risk. The study group was composed of 102 women and 67 men with type 2 diabetes, having their glycemic and metabolic parameters assessed. All were on oral antidiabetic drugs. Serum levels of NT-proBNP and PIGF-1 were measured by electro-hemi-luminescence on an Elecsys 2010 analyzer. Enzymatic immunoassays were used for ADMA and ET-1. The Framingham Risk Score (FRS), the UKPDS 2.0 and the ADVANCE risk engines were used to calculate cardiovascular risks while statistical analysis was performed on SPSS. Levels of PIGF-1 showed no correlation with the calculated CV risks. The same was true for ADMA, except for a weak correlation with the UKPDS-based 10-year risk for stroke (Pearsons's R=0.167, p=0.039). Plasma levels of ET-1 were correlated with the UKPDS-based 10-year risk for stroke (R=0.184, p=0.032) and fatal stroke (R=0.215, p=0.012) only. NT-proBNP was significantly correlated with all CV risk calculations: ADVANCE-based 4-yr risk (Spearman's Rho=0.521, p<0.001); UKPDS-based 10-year risk for: CHD (Rho=0.209, p=0.01), fatal CHD (Rho=0.282, p<0.001), stroke (Rho=0.482, p<0.001), fatal stroke (Rho=0.505, p<0.001); and 10-year FRS risk (Rho=0.246, p=0.002). In conclusion, ADMA and PIGF-1 did not seem useful in stratifying CV risk while ET-1 is linked to the risk of stroke, and NT-proBNP to all CV risk estimations.

Evaluation of cardiovascular risk in stages of gout by a complex multimodal ultrasonography.

The aim of our work was to assess ultrasound features of cardiovascular (CV) risk in stages of gout. Cross-sectional complex multimodal ultrasound study of 169 age-matched patients, with similar distribution of arterial hypertension, diabetes mellitus, obesity and chronic renal failure, was divided into four groups: 41 with asymptomatic hyperuricemia, 52 gout without tophi, 42 gouty tophi and 34 controls with osteoarthritis. Parameters independently associated with CV risk were measured: renal resistive index (RRI), left ventricular mass index (LVMi), mitral annulus early diastolic velocity (e'), intima-media thickness (IMT) and common carotid artery resistive index (CCARI). Multivariate analyses were performed to evaluate the impact of gout stages and CV risk factors on ultrasound alterations. Gouty tophi increased the risk of having IMT >0.90 mm with an OR 11.51 (95 % CI 2.32-57.21, p = 0.003), gout without tophi raised the risk with an OR 6.25 (95 % CI 1.37-28.44, p = 0.018), while asymptomatic hyperuricemia had no effect on IMT. The category of CCARI >0.70 was influenced by tophi with an OR 11.18 (95 % CI 2.61-47.83, p = 0.001) and by arterial hypertension with an OR 3.22 (95 % CI 1.11-9.36, p = 0.032). Neither asymptomatic hyperuricemia nor gout without tophi modified the development of abnormally high CCARI. Gout stages had no impact on LVMi, e' and RRI. Tophi are related to worsened ultrasonographic parameters evaluating target organs in gout, relative to earlier stages of the disease. They create a strong risk of carotid arteries' changes even beyond arterial hypertension.

Ultrasonographic measurement of carotid artery resistive index and diastolic function of the heart in gout patients.

The aim of the study was to establish the functional disorder in the blood circulation of gout patients with a method that shows early damage of the heart and vascular structures. A total of 117 patients were examined cross-sectionally by a complex multimodal ultrasonography and were divided into four groups: 37 healthy controls, 24 asymptomatic hyperuricemia, 36 gout without tophi and 20 gouty tophi. With pulsed Doppler, common carotid artery resistive index (CCARI) and parameters of the transmitral blood flow were determined: the ratio between maximal early and late flow velocities (E/A ratio) and deceleration time (DT). With tissue Doppler imaging, mitral annular peak velocity (Em) was obtained. In the examined ultrasonographic parameters between healthy controls and the three patient groups, there was a statistically significant difference (p < 0.001). Comparing asymptomatic hyperuricemia and gout without tophi, no significant difference in CCARI (p = 0.656), E/A ratio (p = 0.472), DT (p = 0.990) and Em (p = 0.488) was found. Gouty tophi in comparison with gout without tophi and asymptomatic hyperuricemia had significantly lower Em (mean ± SD 0.07 ± 0.02 vs 0.09 ± 0.03 vs 0.13 ± 0.17) and significantly higher CCARI (mean ± SD 0.74 ± 0.05 vs 0.70 ± 0.05 vs 0.69 ± 0.05). Further multiple logistic regression revealed that tophi increased subject's likelihood of having category of CCARI ≥ 0.7 with an OR = 10.91 (95 % CI 1.80-66.14, p = 0.009), while the category of Em < 0.08 m/s was influenced by renal insufficiency with an OR = 3.07 (95 % CI 1.17-8.02, p = 0.022). Gouty tophi are associated with progression of arteriosclerotic-type vessel changes. Worsening of diastolic dysfunction of the heart is independently associated with renal insufficiency. In terms of CV risk, tophi are an indicator of its increase.

Case Report: Transthyretin Glu54Leu-a rare mutation with predominant cardiac phenotype.

We report two unrelated Bulgarian families with hereditary transthyretin (ATTR) amyloidosis due to a rare p.Glu74Leu (Glu54Leu) pathogenic variant found in seven individuals-three of them symptomatic. Only one family with the same variant and with a Swedish origin has been clinically described so far. Our patients are characterized by predominant cardiac involvement, very much similar to the Swedish patients. Although the initial complaint was bilateral carpal tunnel syndrome, advanced amyloid cardiomyopathy was found in two symptomatic carriers at diagnosis with heart failure manifestations. The neurological involvement was considered as mild, with mainly sensory signs and symptoms being present. We followed a non-biopsy algorithm to confirm the diagnosis. Tafamidis 61 mg has been initiated as the only approved disease modifying treatment for ATTR cardiomyopathy. Clinical stability in the absence of adverse events has been observed at follow up.