Antihypertensive Effects of Statins: A Meta‐Analysis of Prospective Controlled Studies

In experimental studies, statins have been shown to lower blood pressure through increased nitric oxide bioavailability and improved arterial compliance. The clinical significance of this effect remains poorly documented. The authors performed a meta‐analysis of the effect of statins on systolic blood pressure (SBP) and diastolic blood pressure (DBP) including prospective randomized, controlled trials of statin therapy. EMBASE and MEDLINE searches for studies in which patients were randomized to treatment with a statin plus standard treatment (or placebo) vs standard treatment (or placebo) were conducted. Studies that provided data on SBP and DBP values before the initiation of the treatment and at the end of the follow‐up period were included. A total of 40 studies with 51 comparison groups examining 22,511 controls and 22,602 patients taking statins were examined. Mean SBP in the statin group decreased by 2.62 mm Hg (95% confidence interval [CI], −3.41 to −1.84; P<.001) and DBP by 0.94 mm Hg (95% CI, −1.31 to −0.57; P<.001). In studies including hypertensive patients, the decrease in blood pressures with statins was slightly greater (SBP, −3.07 mm Hg; 95% CI, −4.00 to −2.15 and DBP, 1.04; 95% CI, −1.47 to −0.61). Similarly, statins effectively reduced SBP in diabetic patients. In this large meta‐analysis of prospective controlled studies, the authors found a small but statistically significant reduction of SBP in patients taking statins. The decrease in blood pressure may contribute to the pleiotropic effect of statins in reducing cardiovascular risk.

Statins have pleiotropic effects such as improving endothelial‐dependent vasodilation, increasing bioavailability of nitric oxide, and reducing levels of endothelin‐1 (potent vasoconstrictor).¹ Statins also downregulate expression of angiotensin type 1 receptors, decrease expression of NAD(P)H oxidase subunit p22phox, and reduce free radical release in the vasculature² and have been shown to improve arterial compliance.³ These pleiotropic effects may directly lower blood pressure (BP) in addition to lowering cholesterol levels.³ Previous studies report a positive correlation between BP and cholesterol levels. Indirect evidence from several trials investigating cholesterol‐lowering regimens suggests that lowering cholesterol may simultaneously reduce BP by between 2 mm Hg and 5 mm Hg.⁴ However, conflicting results have been reported with respect to BP‐lowering effects of statins in humans.⁴ The present study was designed to systematically review prospective randomized trials and assess the antihypertensive effects of statins.     

Effects of direct infusion of bone marrow-derived progenitor cells and indirect mobilization of hematopoietic progenitor cells on atherosclerotic plaque and inflammatory process in atherosclerosis

Background

We sought to investigate the effects of lin −/sca + cells, endothelial progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF) administration on atherosclerotic plaque progression.

Methods

Apolipoprotein E-deficient (apoE^−/−) mice were splenectomized and treated with high-cholesterol diet for 6 weeks in order to induce atherosclerotic plaque development. Bone marrow-derived Lin −/sca-1 + cells were isolated and further cultured to early growth endothelial progenitor cells (EPCs). Mice were divided in four groups (n = 10/group) and received two intravenous injections of 5 × 10⁵ cells (lin −/sca-1 + or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 μg/kg/day) for 7 days or normal saline. The same interventions were administered to animals, which had undergone unilateral hind-limb ischemia. Effects on inflammatory parameters, lesion severity, and atherosclerotic plaque area size were assessed.

Results

The administration of both G-CSF and progenitor cells significantly decreased the levels of IL-6, 6 weeks after the initiation of treatment. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94% ± 3.68, p = 0.001), by lin −/sca-1 + (23.27% ± 5.98, p = 0.002) and cultured EPCs (23.16 ± 4.86%, p = 0.002) compared to control (32.75% ± 7.05). In the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque area, was not significantly different between the treatment groups cultured EPCs-treated mice and the control group (p = NS, for all).

Conclusions

Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells decreased plaque progression and levels of inflammatory molecules in a murine model of atherosclerosis. Treatment with G-CSF, lin −/sca-1 +, or EPCs may exert beneficial effects on vascular inflammation and atherosclerotic plaque progression. However, the effects are diminished in an ischemic setting.     

The relationship between depressive symptoms, illness perceptions and quality of life in ankylosing spondylitis in comparison to rheumatoid arthritis

Anxiety and depressive symptoms as well as cognitive variables are important in determining outcome in rheumatic diseases. We aimed to compare psychological distress symptoms and illness perceptions in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and to test whether their associations with health-related quality of life (HRQoL) were similar in these rheumatologic disorders. In 55 AS and 199 RA patients, we administered the Patient Health Questionnaire (PHQ-9), the Symptom Check-List and the Brief-Illness Perception Questionnaire to assess psychological variables and the World Health Organization Quality of Life Instrument, Short Form to assess HRQoL. We used hierarchical regression analyses to determine the associations between psychological variables and HRQoL after adjusting for demographic variables and disease parameters. The prevalence of clinically significant depressive symptoms (PHQ-9?≥?10) was 14.8 % in AS and 25.1 % in RA patients, but adjustment for demographics rendered these differences in depressive symptoms’ severity non-significant. Psychological distress levels and HRQoL were similar in both disorders. Illness concern (b?=??0.37) was the only significant independent correlate of physical HRQoL in AS. In RA, depression (b?=??0.25), illness concern (b?=??0.14) and worries about the consequences of the disease (b?=??0.31) were the independent correlates of physical HRQoL. These findings suggest that cognitive variables are important correlates of HRQoL in AS, whereas in RA depressive symptoms and illness perceptions equally contribute to HRQoL. Our data encourage the design of psychotherapeutic trials targeting disease-related cognitions in AS in an attempt to improve patient’s physical HRQoL.     

Weekly chemotherapy with carboplatin,docetaxel and irinotecan in advanced non-small-cell-lung cancer: a phase II study

The aim of this study was to evaluate the efficacy and tolerability of carboplatin, docetaxel plus irinotecan given weekly to patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). 50 patients with previously untreated NSCLC (stage IIIB 10; stage IV 40; 44% squamous cell carcinoma; median Eastern Cooperative Oncology Group (ECOG) status 1) received intravenous (i.v.) carboplatin area under the curve (AUC) 2, docetaxel 20 mg/m(2) and irinotecan 60 mg/m(2) on days 1, 8 and 15, repeated every 5 weeks. Prophylactic granulocyte colony-stimulating factor (G-CSF) 150 ug/m(2) was given from days 3 to 6 and 10 to 13. Response was evaluated every two cycles. Four complete responses (8%) and 24 (48%) partial responses were observed, giving an overall intent-to-treat response rate of 56%. 8 patients (16%) achieved stable disease and 14 (28%) progressed. The median time to progression (TTP) was 9.6 months (range 2.5-21.8 months), median survival was 14.8 months (range 0.3-27+ months) and actuarial 1-year survival time was 55%. Grade 3/4 anaemia and thrombocytopenia occurred in 18 and 22% of patients, respectively; 13 patients (26%) developed grade 3/4 neutropenia and 7 (14%) had neutropenic fever that required hospitalisation, but was successfully treated with antibiotics and G-CSF support. One patient developed a severe allergy during docetaxel administration and was withdrawn. Other grade 3/4 adverse events included diarrhoea (n=14; 3 required hospitalisation), nausea/vomiting (n=9), neurotoxicity (n=5) and fatigue (n=5). 6 patients required a dose reduction. This combination of i.v. carboplatin AUC 2, docetaxel 20 mg/m(2) and irinotecan 60 mg/m(2) given weekly is highly effective in the treatment of chemotherapy-na?ve advanced NSCLC. Toxicity was moderate, but manageable.     

Epigenetic inactivation of DNA repair in breast cancer

The study of epigenetic mechanisms in cancer, such as DNA methylation and histone modifications, has revealed a plethora of events that contribute to cancer through stable changes in the expression of genes critical to transformation pathways. In this mini review we look at the different epigenetic modifications prevalent in this neoplastic phenotype, focusing on breast cancer. Most encouragingly, research in epigenetics has led to improved survival of patients with certain forms of lymphoma and leukemia through the use of drugs that alter DNA methylation and histone acetylation. Thus, we look at the clinical utility of targeting epigenetic pathways. In addition, we explore numerous other clinical applications of epigenetics, in areas such as cancer screening and early detection, prevention, classification for epidemiology and prognostic purposes, and predicting outcomes after standard therapy.     

COVID-19 and the heart

An outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a strain of SARS-CoV. Patients infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms, cough, fever and fatigue to severe lung injury, appearing as bilateral interstitial pneumonia or acute respiratory failure. Although SARS-CoV-2 infection predominantly offends the respiratory system, it has been associated with several cardiovascular complications as well. For example, patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary infection. The incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases, whereas heart failure (HF) may develop due to infiltration of the heart by inflammatory cells, destructive action of pro-inflammatory cytokines, micro-thrombosis and new onset or aggravated endothelial and respiratory failure. Lastly, SARS-CoV-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary, through respiratory failure or severe respiratory distress syndrome. In this comprehensive review we summarize the COVID-19 related cardiovascular complications (acute coronary syndromes, myocarditis, HF, arrhythmias) and discuss the main underlying pathophysiological mechanisms.     

The role of epigenetics in childhood autoimmune diseases with hematological manifestations

Autoimmune diseases with hematological manifestations are often characterized by chronicity and relapses despite treatment,and the underlying pathogenetic mechanisms remain unknown.Epigenetic alterations play a vital role in the deregulation of immune tolerance and the development of autoimmune diseases.In recent years,study of epigenetic mechanisms in both adult and childhood autoimmune disorders has been seeking to explain the pathophysiology of these heterogeneous diseases and to elucidate the interaction between genetic and environmental factors.Various mechanisms,including DNA methylation,histone modifications(chromatin remodeling),and noncoding RNAs(ncRNAs),have been studied extensively in the context of autoimmune diseases.This paper summarizes the epigenetic patterns in some of the most common childhood autoimmune disorders with hematological manifestations,based on epigenetic studies in children with primary immune thrombocytopenia(ITP),systemic lupus erythematosus(SLE),and juvenile idiopathic arthritis(JIA).Research findings indicate that methylation changes in genes expressed on T cells,modifications at a variety of histone sites,and alterations in the expression of several ncRNAs are involved in the pathogenesis of these diseases.These mechanisms not only determine the development of these diseases but also affect the severity of the clinical presentation and biochemical markers.Further studies will provide new tools for the prevention and diagnosis of childhood autoimmune disorders,and possible novel treatment options.     

A palmitoylated peptide,derived from the acidic carboxyl-terminal segment of the integrin αIIb cytoplasmic domain,inhibits platelet activation

Platelet integrin α_IIbβ₃ contains an acidic membrane distal motif, 1000LEEDDEEGE1008, in the cytoplasmic domain of the α_IIb subunit. We showed that a lipid-modified peptide corresponding to the above region, palmitoyl-K-LEEDDEEGE (pal-K-1000-1008), is platelet permeable and has inhibited platelet aggregation induced by 0.4 U/ml of thrombin (IC50 = 164 µM). Moreover the peptide inhibited both Fibrinogen and PAC-1, binding to activated platelets. The non palmitoylated analog was inactive. A modified, scrambled acidic peptide (palmitoyl-K-GDDEELEEE), showed significant lower inhibitory activity than pal-K-1000-1008. A palmitoylated peptide corresponding to the membrane proximal cytoplasmic domain of α_IIb, 989KGVFFKR995 (pal-989-995), is known to specifically induce platelet aggregation. Pal-K-1000-1008 was an inhibitor of human washed platelet aggregation induced by pal-K-989-995 (IC50 = 15 µM). Moreover, pal-K-1000-1008 inhibited phosphorylation of ERK and FAK, two protein kinases involved in platelet activation and aggregation. Our results favour the assumption that the interaction of the membrane proximal sequence 989KGVFFKR995 of the cytoplasmic domain of α_IIb with the acidic terminal 1000LEEDDEEGE1008 motif may be an important structural factor in platelet signaling, leading to platelet activation and aggregation.     

Spontaneous coronary artery dissection: A review of diagnostic methods and management strategies

Spontaneous coronary artery dissection (SCAD) is a rare non-atherosclerotic cause of acute coronary syndromes defined as non-iatrogenic, non-traumatic separation of the coronary artery wall. The most common profile is a middle-aged woman between 44 and 53 years with few cardiovascular risk factors. SCAD is frequently linked with predisposing factors, such as postpartum, fibromuscular dysplasia or other vasculopathies, connective tissue disease and hormonal therapy, and it is often triggered by intense physical or emotional stress, sympathomimetic drugs, childbirth and activities increasing shear stress of the coronary artery walls. Patients with SCAD usually present at the emergency department with chest discomfort, chest pain, and rapid heartbeat or fluttery. During the last decades, the most common problem of SCAD was the lack of awareness about this condition which has led to significant underdiagnosis and misdiagnosis. However, modern imaging techniques such as optical coherence tomography, intravascular ultrasound, coronary angiography or magnetic resonance imaging have contributed to the early diagnosis of the disease. Treatment of SCAD remains controversial, especially during the last years, where invasive techniques are being used more often and in more emergent cardiac syndromes. Although conservative treatment combining aspirin and beta-blocker remains the recommended strategy in most cases, revascularization could also be suggested as a method of treatment in specific indications, but with a higher risk of complications. The prognosis of SCAD is usually good and long-term mortality seems to be low in these patients. Follow-up should be performed on a regular basis.