An examination of the effect of combined cyclical hormone replacement therapy on lipoprotein(a) and other lipoproteins

Lipoprotein(a) (Lp(a)) is an independent marker of cardiovascular disease which is relatively unresponsive to treatment with most of the commonly prescribed lipid lowering drugs. Concentrations of Lp(a) increase after the menopause, and the primary aim of this study was to determine whether combined hormone replacement therapy was effective in lowering levels of Lp(a) in postmenopausal women. An open longitudinal study was conducted among 42 women who had undergone a spontaneous menopause and were attending the outpatient clinic of the Prince of Wales Hospital, Hong Kong. All subjects were treated with 2 mg oral estradiol daily and 5 mg medroxyprogesterone acetate for 12 days each calendar month. Fasting blood samples for lipoprotein measurement were taken before the commencement of treatment and at 6 and 12 months. Lp(a) levels showed a skewed distribution with a median value before treatment of 9.45 mg/dl (range 1.47-95.62 mg/dl). After 6 months, there was a reduction to 7.70 mg/dl (1.12-72.59 mg/dl) (P < 0.01), and after 12 months the median concentration was 7.14 mg/dl (0.63-69.23 mg/dl) (P < 0.001 0-12 months). There were also significant reductions in the concentrations of apo B from 116.13 to 111.62 mg/dl and LDL-C from 3.02 to 2.74 mmol/l (P < 0.05), plus a lowering of TC of borderline significance. Apo A-I increased from 162.56 to 173.35 mg/dl (P < 0.01), but there were no significant changes in HDL-C or the HDL-C subfractions. TC, LDL-C, apo B and TG concentrations were higher and HDL-C and HDL2-C concentrations were lower when blood was sampled during combined treatment with estrogen and progesterone than when estrogen was being taken alone. Levels of Lp(a) were also lower during the estrogen only phase of treatment, but none of these differences were statistically significant. This study demonstrates that combined cyclical hormone replacement therapy is effective in reducing concentrations of Lp(a). The trend towards a more atherogenic lipid profile during the combined phase of treatment suggests that attention should be given to the timing of blood sampling in future studies of this nature

IgD multiple myeloma with thoracic spine compression due to epidural extra-osseous tumour spread

On initial presentation of a patient with IgD multiple myeloma there were no features to suggest an unusual variant. Two months later she developed spinal cord compression due to an IgD plasmacytoma. This complication of IgD myeloma has rarely been reported. During the course of the disease and using the routine laboratory protocol for investigating and identifying paraproteins, including IgD, the patient's results became indistinguishable from those in Bence-Jones proteinuria myeloma.link_to_subscribed_fulltex

Epidemiology of cardiovascular risk factors in Hong Kong

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Is alcohol beneficial or harmful for cardioprotection?

While the effects of chronic ethanol consumption on liver have been well studied and documented, its effect on the cardiovascular system is bimodal. Thus, moderate drinking in many population studies is related to lower prevalence of coronary artery disease (CAD). In contrast, heavy drinking correlates with higher prevalence of CAD. In several other studies of cardiovascular mortalities, abstainers and heavy drinkers are at higher risk than light or moderate drinkers. The composite of this disparate relation in several population studies of cardiovascular mortality has been a “U-” or “J-”shaped curve. Apart from its ability to eliminate cholesterol from the intima of the arteries by reverse cholesterol transport, another major mechanism by which HDL may have this cardioprotective property is by virtue of the ability of its component enzyme paraoxonase1 (PON1) to inhibit LDL oxidation and/or inactivate OxLDL. Therefore, PON1 plays a central role in the disposal of OxLDL and thus is antiatherogenic. Furthermore, PON1 is a multifunctional antioxidant enzyme that can also detoxify the homocysteine metabolite, homocysteine thiolactone (HTL), which can pathologically cause protein damage by homocysteinylation of the lysine residues, thereby leading to atherosclerosis. We demonstrated that moderate alcohol up regulates liver PON1 gene expression and serum activity, whereas heavy alcohol consumption had the opposite effects in both animal models and in humans. The increase in PON1 activity in light drinkers was not due to preferential distribution of high PON1 genotype in this group. It is well known that wine consumption in several countries shows a remarkable inverse correlation to local rates of CAD mortality. Significantly, apart from its alcohol content, red wine also has polyphenols such as quercetin and resveratrol that are also known to have cardioprotective effects. We have shown that quercetin also up regulates PON1 gene in rats and in human liver cells. The action of quercetin seems to be mediated via the active form of the nuclear lipogenic transcription factor, sterol-regulatory element-binding protein 2 (SREBP2) that is translocated from endoplasmic reticulum to the nucleus. However, the mechanism of action of ethanol-mediated up-regulation of PON1 gene remains to be elucidated. We conclude that both moderate ethanol and quercetin, the two major components of red wine, exhibit cardioprotective properties via the up-regulation of the antiatherogenic gene PON1