Despite the use of statins, familial hypercholesterolemia (FH) patients often have increased LDL-cholesterol (Ch) and high risk for atherosclerotic cardiovascular disease (ASCVD). This study aimed to ...analyze the effect of statin therapy on attainment of LDL-Ch treatment targets and appearance of new ASCVD and diabetes in FH patients.
This study is a retrospective analysis of data from medical records of 302 FH patients treated continuously with statins during 3 years. At baseline and once yearly, anthropometric measurements, lipids (total Ch, LDL-Ch, HDL-Ch, triglycerides, apoliporotein A1 and B), fasting plasma glucose, and insulin were determined.
In FH patients, high intensity statin was prescribed only in 17.9% of cases. LDL-Ch levels were significantly lower after 3 years of statin treatment (3.61 ± 1.19 mmol/l) vs. baseline (4.51 ± 1.69 mmol/l; p < 0.01), but only 6.9% of FH patients reached the recommended ≥50% LDL-Ch reduction and 16.2% attained the LDL-Ch <2.6 mmol/l target. Simultaneously, 9.6% of FH patients developed new ASCVD, with lower HDL-Ch after 3 years of statin treatment than in those who remained free of ASCVD. In addition, we observed new onset diabetes in 6.4% of FH patients who were more obese, older and with higher fasting glucose at baseline than FH patients free of diabetes, regardless of the type of statin.
These results imply that only a small proportion of FH patients achieved the recommended LDL-Ch treatment targets, mostly due to the use of low statin dose and infrequent implementation of high-intensity statin treatment, which altogether could not prevent the increase in residual cardiovascular risk.
•A small proportion of familial hypercholesterolemia (FH) patients achieved the recommended LDL-Ch treatment targets.•High intensity statin was prescribed in only 17.9% of FH patients.•9.6% of FH patients developed new atherosclerotic cardiovascular disease (ASCVD) during the 3 years of statin treatment.•New onset diabetes was diagnosed in 6.4% of statin treated FH patients.
Hyperglycemia has detrimental effect on ischemic myocardium, but the impact of acute hyperglycemia on the myocardium in asymptomatic diabetic patients has not been fully elucidated. Thus, this ...follow-up study was aimed to investigate the effects and reversibility of acute hyperglycemia on regional contractile function of left ventricle (LV) in diabetic patients without cardiovascular disease.
The two-dimensional speckle tracking echocardiography (2D-STE), including multilayer strain analysis, was used for evaluation of global and regional LV function in asymptomatic, normotensive patients with uncomplicated diabetes, with acute hyperglycemia ( ≥ 11.1 mmol/l) (Group A, n = 67), or with optimal metabolic control (fasting plasma glucose < 7 mmol/l and HbA1c < 7%) (Group B, n = 20), while 20 healthy individuals served as controls (Group C). In group A, after 72 h of i.v. continuous insulin treatment (at the time euglycemia was achieved) (second examination) and after 3 months following acute hyperglycemia (third examination) 2D-STE was repeated.
Global longitudinal strain (GLS) (- 19.6 ± 0.4%) in Group A was significantly lower in comparison to both groups B (- 21.3 ± 0.4%; p < 0.05) and C (- 21.9 ± 0.4%; p < 0.01) at baseline, while we could not detect the differences between groups B and C. Peak systolic longitudinal endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) layer strain were significantly lower in group A at baseline compared to both groups B and C. Deterioration in peak systolic circumferential strain was observed at basal LV level, in all three layers (Endo, Mid and Epi) and in mid-cavity LV level in Epi layer in group A in comparison to group C. Moreover, in group A, after euglycemia was achieved (at second and third examination) GLS, as well as peak longitudinal and circumferential strain remain the same.
Acute hyperglycemia in asymptomatic diabetic patients has significant negative effects on systolic LV myocardial mechanics primarily by reducing GLS and multilayer peak systolic longitudinal and circumferential strain which was not reversible after three months of good glycemic control.
•Coronary ED is associated with insulin resistance.•Coronary ED is also associated with impairments in insulin secretory response.•Decreases in LDL particle size, not the total LDL-Ch, influences ...coronary ED.•Coronary ED is also influenced by impaired fibrinolysis.
This study was aimed to compare insulin sensitivity and secretion response, lipoprotein and plasminogen activator inhibitor 1 (PAI-1) levels between the subjects with and without coronary artery endothelial dysfunction (ED).
ED was detected by intracoronary injection of acetylcholine (ACh) in 47 nondiabetes subjects without stenotic coronary arteries, selected from 316 consecutive patients with coronary angiography performed for suspected coronary artery disease. The subjects were divided into two groups: presence of ACh-induced coronary spasm (group ED+, N = 30) and absence of ACh-induced coronary spasm (group ED−, N = 17). Insulin sensitivity (Si) was evaluated by frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis and by HOMA-IR, insulin secretion by acute insulin response (AIR) (calculated from the first 8 min of FSIGTT) and by disposition index (DI) (Si × AIR). Lipids and PAI-1 levels were determined enzymatically, and LDL particle size by gradient gel electrophoresis.
Si was significantly lower (4.22 ± 0.62 vs 6.98 ± 1.47 min−1/mU/l × 104; p < 0.05) while HOMA-IR was significantly higher in ED + group vs ED− group (2.8 ± 0.3 vs 1.7 ± 0.2; p < 0.05). Simultaneously, AIR and DI was significantly lower in ED + vs ED− groups (p < 0.05 and p < 0.01, respectively). Investigated groups did not differ in fasting lipid levels but ED+ group had significantly smaller LDL particles (p < 0.01) and higher PAI-1 levels (p < 0.05). Regression analysis shown that DI was a strong independent predictor of appearance of ED, together with PAI-1 and LDL particle size.
Both insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes.
This study aimed to analyse the impact of obesity in type 2 diabetes (T2D) on adipocytokines (adiponectin, leptin and resistin) and inflammatory markers (TNF-α, IL-6 and hsCRP) as cardiovascular risk ...factors. A cross-sectional study comparing the basal levels of adipocytokines and inflammatory markers was done in 18 obese (BMI ≥ 30 kg/m²) (group A), 21 overweight (25 kg/m² ≤ BMI < 30 kg/m²) (group B), 25 non-obese T2D patients (group C) and 15 non-obese controls (group D). The lowest levels of adiponectin and the highest levels of leptin, resistin, TNF-α, IL-6 and hsCRP were found in group A. Adiponectin levels were significantly lower, and resistin, TNF-α, and hsCRP levels were elevated in group C vs. D. However, leptin and IL-6 levels differed significantly between groups A and B, but not between groups C and D. Moreover, we found a significant negative correlation between adiponectin and TNF-α, but not with other markers, which was independent of the presence of obesity. In contrast, leptin and resistin correlated with the inflammatory markers, and this correlation was obesity-dependent. Our results suggest that obesity influences cardiovascular risk primarily through changes in leptin and resistin and less efficiently at the level of adiponectin.
This study was aimed at investigating daily fluctuation of PAI-1 levels in relation to insulin resistance (IR) and daily profile of plasma insulin and glucose levels in 26 type 2 diabetic (T2D) ...patients with coronary artery disease (CAD) (group A), 10 T2D patients without CAD (group B), 12 nondiabetics with CAD (group C), and 12 healthy controls (group D). The percentage of PAI-1 decrease was lower in group A versus group B (4.4 ± 2.7 versus 35.0 ± 5.4%; P<0.05) and in C versus D (14.0 ± 5.8 versus 44.7 ± 3.1%; P<0.001). HOMA-IR was higher in group A versus group B (P<0.05) and in C versus D (P<0.01). Simultaneously, AUCs of PAI-1 and insulin were higher in group A versus group B (P<0.05) and in C versus D (P<0.01), while AUC of glucose did not differ between groups. In multiple regression analysis waist-to-hip ratio and AUC of insulin were independent determinants of decrease in PAI-1. The altered diurnal fluctuation of PAI-1, especially in T2D with CAD, might be strongly influenced by a prolonged exposure to hyperinsulinemia in the settings of increased IR and abdominal obesity, facilitating altogether an accelerated atherosclerosis.
Summary
Background
: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP) is a risk factor for the peripheral arterial disease (PAD) in diabetes. This study aimed to ...evaluate the possible predictive significance of hs-CRP for the development and progression of PAD in patients with type 2 diabetes (T2D).
Methods
: The study included 80 patients previously diagnosed with T2D, aged 45–70 years, divided into
group A
(T2D patients with PAD; n=38) and
group B
(T2D patients without PAD; n=42). After five years, all the patients were re-examined and divided into subgroups depending on
de novo
development of PAD or progression of previously diagnosed PAD. Ankle-Brachial Index (ABI) measurement was used for PAD diagnosis and hs-CRP was determined by nephelometry.
Results
: We found significantly higher hs-CRP levels in group A compared to group B, but only at baseline. Among the patients in group A, those with later progression of PAD (subgroup A1) had the highest levels of hs-CRP at baseline, although not significantly different from those in subgroup A2 (non-progressors). In contrast, hs-CRP level was significantly higher in subgroup B1 (progressors) in comparison to subgroup B2 (non-progressors) at both the first and second exam. Of all the investigated metabolic parameters, hs-CRP was the only independent predictor of PAD progression (OR=0.456, 95% CI=0.267–0.7815, p=0.004). The cut-off point for hs-CRP was 2.5 mg/L (specificity 75% and sensitivity 73.3%) with the relative risk for PAD of 2.93 (95% CI=1.351–6.3629).
Conclusions
: Our study implies that hs-CRP can be used as a reliable predictor for the progression of PAD in patients with T2D.
Stationary field experiment pertaining to the winter wheat in Croatia was performed during the three seasons. This study’s intention was to examine and diagnose the effect of tillage systems (TS) on ...soil chemical properties (soil acidity, phosphorus P, potassium K, and organic matter content). The TSs were as follows: CT — ploughing up to 30 cm depth, DT — disking up to 8-12 cm depth, LT — loosening up to 35 cm depth, and NT — no-tillage. The experimental design was a randomised block design in four repetitions, in which the basic TS plot amounted to 540 m2. Soil sampling for 0-30 cm soil layer was performed prior to setting up the experiment and subsequent to the three seasons with a total of 320 soil samples. Chemical analysis was performed according to standard pedological procedures. Economic indicators were calculated using economic equations and standards, whereas statistical analysis was performed with SAS 9.3 and Microsoft Excel 2016. Generated results indicate that the expressed accumulation of phosphorus and potassium appeared with a distinct vertical stratification in the systems with shallower tillage or no-tillage. At the same time, these TSs ensured the soil organic matter and soil fertility preservation. A conservable agricultural production of reduced soil tillage systems has its efficiency and vigor while providing soil degradation.
Stacionarni poljski pokus za ozimu pšenicu u Hrvatskoj proveden je tijekom triju sezona . Namjera ovoga istraživanja bila je ispitati i dijagnosticirati utjecaj sustava obrade tla (TSs) na kemijska svojstva tla (kiselost tla, sadržaj fosfora, kalija i organske tvari. TSs-i su bili CT — oranje do 30 cm dubine; DT — tanjuranje do 8-12 cm dubine; LT — rahljenje do 35 cm dubine; NT — bez obrade tla. Eksperimentalni dizajn je bio randomizirani blok dizajn u četiri ponavljanja, u kojem je osnovna TSs parcela bila 540 m2 . Uzorkovanje za sloj tla 0-30 cm obavljeno je prije postavljanja pokusa i nakon triju sezona s ukupno 320 uzoraka tla. Kemijska analiza provedena jer prema standardnim pedološkim postupcima. Standardna statistička analiza provedena softverom SAS 9.3 i Microsoft Excel 2016. Dobiveni rezultati upućuju da se na sustavima s plićom obradom ili bez obrade javlja izražena akumulacija fosfora i kalija uz izraženu vertikalnu stratifikaciju. Istodobno ovi TSs-i osiguravaju konzervaciju organske tvari tla i očuvanje plodnosti tla. Poljoprivredna proizvodnja uz primjenu reduciranih sustava obrade tla ima svoju učinkovitost i snagu kroz sprječavanje degradacije tla.
Anticancer activities of various extracts of the medicinal mushroom, Ganoderma lucidum, have been widely demonstrated and are mainly associated with the presence of different bioactive ...polysaccharides and triterpenoids. We have evaluated and compared in vitro and in vivo the antitumor effects of two preparations from Ganoderma lucidum: a methanol extract containing total terpenoids (GLme) and a purified methanol extract containing mainly acidic terpenoids (GLpme). Both extracts inhibited tumor growth of B16 mouse melanoma cells inoculated subcutaneously into syngeneic C57BL/6 mice and reduced viability of B16 cells in vitro, whereby GLme exhibited stronger effect. Furthermore, anticancer activity of GLme was demonstrated for the first time against two other rodent tumor cell lines, L929-mouse fibrosarcoma and C6-rat astrocytoma. The mechanism of antitumor activity of GLme comprised inhibition of cell proliferation and induction of caspase-dependent apoptotic cell death mediated by upregulated p53 and inhibited Bcl-2 expression. Moreover, the antitumor effect of the GLme was associated with intensified production of reactive oxygen species, whereas their neutralization by the antioxidant, N-acetyl cysteine, resulted in partial recovery of cell viability. Thus, our results suggest that GLme might be a good candidate for treatment of diverse forms of cancers.