A 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia

BACKGROUND: Although the effect of statins on lowering low-density lipoprotein cholesterol (LDL-C) has been extensively studied, their hypotriglyceridemic capacity is not fully understood. OBJECTIVE: The present study examined clinical and laboratory factors potentially associated with the triglyceride (TG)-lowering effect of rosuvastatin. METHODS: Eligible patients had primary dyslipidemia and a moderate risk of heart disease. Patients were prescribed rosuvastatin 10 mg/d in an open-label fashion and kept 3-day food diaries. Laboratory measurements, performed at baseline and 12 weeks, included serum lipid parameters (total cholesterol [TC], TGs, LDL-C, high-density lipoprotein cholesterol [HDL-C], and apolipoprotein [apo] levels), non-lipid metabolic variables (including carbohydrate metabolism parameters and renal, liver, and thyroid function tests), and LDL-subfraction profile (by high-resolution 3% polyacrylamide gel electrophoresis). Tolerability was assessed at each visit. RESULTS: Participants were 75 hyperlipidemic patients (39 men and 36 women; mean age, 51.7 years). At 12 weeks, TC levels were reduced by 35.1% (P < 0.001), TGs by 15.2% (P < 0.001), LDL-C by 48.5% (P < 0.001), apoE by 35.4% (P < 0.001), and apoE by 17.3% (P < 0.001) from baseline, whereas HDL-C and apoA1 levels were not significantly changed. Stepwise linear regression analysis showed that baseline TG levels were most significantly correlated (R(2) = 42.0%; P < 0.001) with the TG-lowering effect of rosuvastatin, followed by the reduction in apoCIII levels (R(2) = 13.6%; P < 0.01). Rosuvastatin use was associated with a reduction in cholesterol mass of both large LDL particles (mean [SD], from 150.5 [36.6] to 90.5 [24.3] mg/dL; P < 0.001) and small, dense LDL (sdLDL) particles (from 11.5 [8.4] to 6.6 [4.5] mg/dL; P < 0.001). Rosuvastatin had no effect on cholesterol distribution of the LDL subfractions (mean [SD], large particles, from 90.8% [7.0%] to 91.8% [5.1%]; sdLDL, from 7.1% [4.7%] to 7.5% [4.8%]) or the mean LDL particle size (from 26.5 [4.2] to 26.6 [4.0] rim). A significant increase in mean LDL particle size after rosuvastatin treatment (mean [SD], from 26.4 [0.4] to 26.9 [0.4] rim; P = 0.02) was observed only in patients with baseline TG levels > or =120 mg/dL. No serious adverse events requiring study treatment discontinuation were reported. One patient who presented with headache and 2 patients who presented with fatigue quickly recovered without discontinuing rosuvastatin treatment. A posttreatment elevation in aminotransferase levels <3-fold the upper limit of normal (ULN) was recorded in 5 (6.7%) patients, and 2 (2.7%) patients experienced elevated creatine kinase concentrations <5-fold ULN. CONCLUSION: Baseline TG levels were the most important independent variable associated with the TG-lowering effect of rosuvastatin.     

Role of immune interferon in the monocytic differentiation of human promyelocytic cell lines induced by leukocyte conditioned medium

Conditioned medium (CM) from lectin-stimulated human leukocytes contains factors that induce human promyelocytic cell lines to differentiate along the monocytic pathway. In this report, we show that human promyelocytic cell lines are also induced to differentiate along this pathway by immune interferon (IFN gamma). Various preparations of IFN alpha tested did not induce this differentiation. In cultures containing IFN gamma, the cells are induced to coordinately express monocyte markers and functions such as monocyte-specific surface antigens, HLA-DR antigens, nonspecific esterase, receptors for the Fc fragment of IgG, and the ability to mediate antibody-dependent cell- mediated cytotoxicity. Our data indicate that differentiation induced by IFN gamma is not secondary to an arrest of growth of promyelocytic cell lines, but rather that a proportion of cells is induced along a programmed pathway of terminal differentiation similar to that of normal monocytes. CM contains IFN gamma, but its ability to induce differentiation is greater than expected on the basis of its content of IFN gamma. Treatments at 56 degrees C or at pH 2.0, which abolish IFN gamma activity, abrogate the differentiation ability of CM. The antiviral activity and the differentiation activity contained in the CM are coeluted from gel filtration and reverse-phase columns. Monoclonal antibodies anti-IFN gamma, which completely abrogate the differentiation ability of IFN gamma and the antiviral activity in the CM, completely suppress the induction of some monocyte markers by CM, but only reduce the expression of others. When IFN gamma is added to CM, promyelocytic cell lines are induced to differentiate to a much greater extent than that induced by either IFN gamma or IFN gamma- depleted CM alone. These results show that the differentiation activity of leukocyte CM is due to the synergistic effect of IFN gamma and other factors not yet identified.     

Serum lipoprotein(a) levels and apolipoprotein(a) isoform size and risk for first-ever acute ischaemic nonembolic stroke in elderly individuals

In a population-based case-control study, we investigated the association of acute ischaemic stroke with lipoprotein(a) (Lp(a)) levels and apolipoprotein (Apo) (a) isoform size in subjects aged older than 70 years. A total of 163 patients with a first-ever-in-a-lifetime acute ischaemic/nonembolic stroke and 166 controls were included. Compared to controls, stroke patients exhibited higher Lp(a) concentrations (median value, 12.2 mg/dl versus 6.4 mg/dl, p < 0.001) and a higher frequency of small Apo(a) isoforms (44.2% versus 29.5%, p < 0.01). Multivariate logistic regression analysis showed a significant association of acute ischaemic stroke with Lp(a) levels [adjusted odds ratio (OR), 1.37, 95% CI (1.12-1.67); p = 0.002], and small Apo(a) isoform size [OR, 1.74 (1.10-3.03); p = 0.04]. Compared to subjects with Lp(a) levels in the lowest quintile, those within the highest quintile had a 3.2-times adjusted risk to suffer an acute ischaemic/nonembolic stroke (1.60-6.62, 95% CI; p < 0.001). Furthermore, analysis of interaction between lipid variables revealed that in the presence of elevated Lp(a) levels the inverse relationship between HDL-cholesterol levels and ischaemic stroke was negated [OR, 1.01 (1.00-1.03); p = 0.015]. Our study suggests that determination of Lp(a) levels and Apo(a) isoform size may be important in identifying elderly individuals at risk of ischaemic stroke independently of other risk factors and concurrent metabolic derangements.     

Elderly patients with non-cardiac admissions and elevated high-sensitivity troponin: the prognostic value of renal function

BACKGROUND High-sensitivity cardiac troponin(hs-cTn) levels are frequently elevated in elderly patients presenting to the emergency department for non-cardiac events. However, most studies on the role of elevated hs-cTn in elderly populations have investigated the prognostic value of hs-cTn in patients with a specific diagnosis or have assessed the relationship between hs-cTn and comorbidities.AIM To investigate the in-hospital prognosis of consecutive elderly patients admitted to the Internal Medicine Department with acute non-cardiac events and increased hs-cTnI levels.METHODS In this retrospective study, we selected patients who were aged ≥ 65 years and admitted to the Internal Medicine Department of our hospital between January 2019 and December 2019 for non-cardiac reasons. Eligible patients were those who had hs-cTnI concentrations ≥ 100 ng/L. We investigated the independent predictors of in-hospital mortality by multivariable logistic regression analysis.RESULTS One hundred and forty-six patients(59% female) were selected with an age range from 65 to 100(mean ± SD: 85.4 ± 7.61) years. The median hs-cTnI value was 284.2 ng/L. For 72(49%) patients the diagnosis of hospitalization was an infectious disease. The overall in-hospital mortality was 32%(47 patients). Individuals who died did not have higher hs-cTnI levels compared with those who were discharged alive(median: 314.8 vs 282.5 ng/L; P = 0.565). There was no difference in mortality in patients with infectious vs non-infectious disease(29% vs 35%). Multivariable analysis showed that age(OR 1.062 per 1 year increase, 95%CI: 1.000-1.127; P = 0.048) and creatinine levels(OR 2.065 per 1 mg/dL increase, 95%CI: 1.383-3.085; P 0.001) were the only independent predictors of death. Mortality was 49% in patients with eGFR 30 mL/min/1.73 m2.CONCLUSION Myocardial injury is a malignant condition in elderly patients admitted to the hospital for non-cardiac reasons. The presence of severe renal impairment is a marker of extremely high in-hospital mortality.