The effects of aromatase inhibitors on lipids and thrombosis

Oestrogen is known to influence blood lipid levels and though its cardioprotective effects are less clear than once thought, there remains concern that reduction of oestrogen levels during hormonal treatment for breast cancer may have an adverse effect on cardiovascular risk. While tamoxifen has been shown to improve lipid profiles, the aromatase inhibitors have a very different mode of action and do not possess the oestrogen-agonistic effects of tamoxifen. At present, there are few data on the effects of these agents on lipid profiles. Available data are mixed, but suggest that the different aromatase inhibitors have different effects on lipid profiles. Some studies show anastrozole as generally having little effect on lipids, while others have indicated adverse effects on lipid profiles/increased hypercholesterolaemia. Letrozole has been associated with adverse effects on lipid profiles in some studies, including BIG 1-98, but short-term data from randomised trials do not show increased cardiovascular morbidity. By contrast, exemestane, which has been studied in slightly more detail, may either have little effect or may be associated with slightly improved lipid profiles. In general, the changes have been small and are likely to be of little relevance in women with advanced breast cancer, but if these agents come to be used in early breast cancer, their impact on lipid profiles may become more important. Many studies are currently underway with the aromatase inhibitors, with safety assessments including monitoring lipid levels. The results of these studies are keenly awaited

Effects of Eprosartan on Serum Metabolic Parameters in Patients with Essential Hypertension

The effect of the anti-hypertensive drug eprosartan on metabolic parameters is currently not extensively documented. We evaluated the effect of eprosartan on parameters involved in atherogenesis, oxidative stress and clotting activity. This open-label unblinded intervention study included 40 adult patients with essential hypertension taking eprosartan. Eprosartan significantly reduced by 8% (p<0.001) the systolic and by 13% (p<.001) the diastolic blood pressure, and in-creased by 24% the time needed to produce oxidative by-products (p=0.001), a marker of oxidative stress. In contrast, ep-rosartan did not alter 8-isoprostane (8-epiPGF2a) levels, another marker of oxidative stress. Additionally, eprosartan re-duced by 14% aspartate aminotransferase and by 21% then alanine aminotransferase activity, while it had a neutral effect on the lipid profile and apolipoprotein levels and did not influence glucose homeostasis, creatinine and uric acid levels. Eprosartan did not affect the clotting/fibrinolytic status (estimated by plasminogen activator inhibitor 1, tissue plasmino-gen activator and a2 antiplasmin levels), or the enzymatic activity of the lipoprotein associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON1). In conclusion, eprosartan should be mainly considered as an anti-hypertensive agent with neutral effects on most of the metabolic parameters in hypertensive patients

Fever as a Cause of Hypophosphatemia in Patients with Malaria

Hypophosphatemia occurs in 40 to 60% of patients with acute malaria, and in many other conditions associated with elevations of body temperature. To determine the prevalence and causes of hypophosphatemia in patients with malaria, we retrospectively studied all adults diagnosed with acute malaria during a 12-year period. To validate our findings, we analyzed a second sample of malaria patients during a subsequent 10-year period. Serum phosphorus correlated inversely with temperature (n = 59, r = −0.62; P<0.0001), such that each 1°C increase in body temperature was associated with a reduction of 0.18 mmol/L (0.56 mg/dL) in the serum phosphorus level (95% confidence interval: −0.12 to −0.24 mmol/L [−0.37 to −0.74 mg/dL] per 1°C). A similar effect was observed among 19 patients who had repeat measurements of serum phosphorus and temperature. In a multiple linear regression analysis, the relation between temperature and serum phosphorus level was independent of blood pH, PCO2, and serum levels of potassium, bicarbonate, calcium, albumin, and glucose. Our study demonstrates a strong inverse linear relation between body temperature and serum phosphorus level that was not explained by other factors known to cause hypophosphatemia. If causal, this association can account for the high prevalence of hypophosphatemia, observed in our patients and in previous studies of patients with malaria. Because hypophosphatemia has been observed in other clinical conditions characterized by fever or hyperthermia, this relation may not be unique to malaria. Elevation of body temperature should be added to the list of causes of hypophosphatemia

Low HDL Cholesterol, Smoking and IL-13 R130Q Polymorphism are Associated with Myocardial Infarction in Greek Cypriot Males. A Pilot Study

This study was carried out in Greek Cypriot males to identify risk factors that predispose to myocardial infarction (MI). Genetic and lipid risk factors were investigated for the first time in a Greek Cypriot male case-control study.Contrary to other studies, mean low density lipoprotein cholesterol did not differ between cases and controls. High density lipoprotein cholesterol on the other hand, although within normal range in cases and controls, was significantly higher in the control population. In agreement with many other studies, smoking was significantly more prevalent in cases compared with controls. In pooled cases and controls, smokers had a significantly lower HDL-C level compared with non-smokers. The frequency of the IL-13 R130Q homozygotes for the mutation (QQ), as well as the mutant allele were significantly higher in cases compared with controls. The IL-13 R130Q variant, or another locus, linked to it, may increase the risk of MI

The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance

The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing transcription factors that have a role in embryonic development, but are primarily known for modulating energy metabolism, lipid storage, and transport, as well as inflammation and wound healing. Currently, there is no consensus as to the overall combined function of PPARs and why they evolved. We hypothesize that the PPARs had to evolve to integrate lipid storage and burning with the ability to reduce oxidative stress, as energy storage is essential for survival and resistance to injury/infection, but the latter increases oxidative stress and may reduce median survival (functional longevity). In a sense, PPARs may be an evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where the ability to store and burn fat is essential for survival, but is a 'double-edged sword', as fats are potentially highly toxic. Ways in which PPARs may reduce oxidative stress involve modulation of mitochondrial uncoupling protein (UCP) expression (thus reducing reactive oxygen species, ROS), optimising forkhead box class O factor (FOXO) activity (by improving whole body insulin sensitivity) and suppressing NFkB (at the transcriptional level). In light of this, we therefore postulate that inflammation-induced PPAR downregulation engenders many of the signs and symptoms of the metabolic syndrome, which shares many features with the acute phase response (APR) and is the opposite of the phenotype associated with calorie restriction and high FOXO activity. In genetically susceptible individuals (displaying the naturally mildly insulin resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated but natural adipose tissue-related inflammatory signal induced by excessive calories and reduced physical activity, which normally couples energy storage with the ability to mount an immune response. This is further worsened when pancreatic decompensation occurs, resulting in gluco-oxidative stress and lipotoxicity, increased inflammatory insulin resistance and oxidative stress. Reactivating PPARs may restore a metabolic balance and help to adapt the phenotype to a modern lifestyle