Hazardous alcohol drinking and premature mortality in Russia: a population based case-control study

David A Leon, Lyudmila Saburova, Susannah Tomkins, Evgueny Andreev, Nikolay Kiryanov, Martin McKee, Vladimir M Shkolnikov.

Summary

Background The reason for the low life expectancy in Russian men and large fl uctuations in mortality are unknown. We investigated the contribution of alcohol, and hazardous drinking in particular, to male mortality in a typical Russian city.

Methods Cases were all deaths in men aged 25–54 years living in Izhevsk occurring between Oct 20, 2003, to Oct 3, 2005. Controls were selected at random from the city population and were frequency matched to deaths by age. Interviews with proxy informants living in the same household as cases were done between Dec 11, 2003, and Nov, 16 2005, and were obtained for 62% (1750/2835) of cases and 57% (1750/3078) of controls. We ascertained frequency and usual amount of beer, wine, and spirits consumed and frequency of consumption of manufactured ethanol-based liquids not intended to be drunk (non-beverage alcohol), and markers of problem drinking. Complete information on markers of problem drinking, frequency of alcohol consumption, education, and smoking was available for 1468 cases and 1496 controls.

Findings 751 (51%) cases were classed as problem drinkers or drank non-beverage alcohol, compared with 192 (13%) controls. The mortality odds ratio (OR) for these men, compared with those who either abstained or were non-problematic beverage drinkers, was 6·0 (95% CI 5·0–7·3) after adjustment for smoking and education. The mortality ORs for drinking non-beverage alcohol in the past year (yes vs no) was 9·2 (7·2–11·7) after adjustment for age. Adjustment for volume of ethanol consumed from beverages lowered the OR to 8·3 (6·5–10·7), and further adjustment for education and smoking reduced it to 7·0 (5·5–9·0). A strong direct gradient with mortality was seen for frequency of non-beverage alcohol drinking independent of volume of beverage ethanol consumed. 43% of mortality was attributable to hazardous drinking (problem drinking or non-beverage alcohol consumption, or both) adjusted for smoking and education.

Interpretation Almost half of all deaths in working age men in a typical Russian city may be accounted for by hazardous drinking. Our analyses provide indirect support for the contention that the sharp fl uctuations seen in Russian mortality in the early 1990s could be related to hazardous drinking as indicated by consumption of non-beverage alcohol.

Antiplatelet Drugs

Aspirin and agents acting on the cyclo-oxygenase pathway

Aspirin irreversibly inhibits cyclo-oxygenase by acetylation of amino acids that are next to the active site. In platelets, this is the rate limiting step in synthesis of thromboxane A2, and inhibition occurs in the megakaryocyte so that all budding platelets are dysfunctional. Because platelets are unable to regenerate fresh cyclo-oxygenase in response, the effect of aspirin remains as long as the lifespan of the platelet (generally about 10 days). A severe weakness of aspirin is that its specificity for cyclo-oxygenase means it has little effect on other pathways of platelet activation. Thus aspirin fails to prevent aggregation induced by thrombin and only partially inhibits that induced by ADP and high dose collagen. Antithrombotic doses used in clinical trials have varied widely from less than 50 mg to over 1200 mg/day, with no evidence of any difference in clinical efficacy. Absorption is over 80% with extensive presystemic metabolism to salicylic acid. Only the parent acetylsalicylic acid has any significant effect on platelet function.

Adverse effects of aspirin include haemorrhage, hypersensitivity and skin rashes, alopecia, and purpura. Sulfinpyrazone also inhibits cyclo-oxygenase (thus producing an aspirin-like state), but is reversible, and also inhibits serotonin uptake by platelets. Iloprost is a prostacyclin analogue that exerts its effects by promoting vasodilatation and inhibiting platelet aggregation induced by ADP, thereby opposing the effects of thromboxane A2.

Dipyridamole

Dipyridamole inhibits phosphodiesterase, thus preventing the inactivation of cyclic AMP, intraplatelet levels of which are increased, resulting in reduced activation of cytoplasmic second messengers. However, it may also exert its effect in other ways, such as stimulating prostacyclin release and inhibiting thromboxane A2 formation. The influence of this drug on these pathways causes reduced platelet aggregability and adhesion in vitro with increased platelet survival in vivo. Its effect is relatively short lasting, and repeated dosing or slow release preparations are needed to achieve 24 hour inhibition of platelet function.

Clopidogrel and Ticlopidine

These thienopyridine derivatives inhibit platelet aggregation induced by agonists such as platelet activating factor and collagen, and also dramatically reduce the binding of ADP to a platelet surface purinoreceptor. The mechanism of this inhibitory action seems to be independent of cyclo-oxygenase. There is also impairment of the platelet response to thrombin, collagen, fibrinogen, and von Willebrand factor. The peak action on platelet function occurs after several days of oral dosing. Adverse effects include evidence of bone marrow suppression, in particular leucopenia, especially with ticlopidine.

Other receptor blockers

Signal transduction generally occurs when specific receptors on the surface are occupied by ligands such as ADP, leading to structural modification of the glycoprotein IIb/IIIa receptor on the surface of the platelet. This is the commonest receptor on the platelet surface and represents the final common pathway for platelet aggregation, resulting in crosslinking of platelets. After intravenous administration of glycoprotein IIb/IIIa receptor inhibitors such as abciximab, platelet aggregation is 90% inhibited within two hours, but function recovers over the course of two days.

The major adverse effect is haemorrhage, and concurrent use of oral anticoagulants is contraindicated. Eptifibatide is a cyclic heptapeptide that mimics the part of the structure of fibrinogen that interacts with glycoprotein IIb/IIIa. Thus it is a fraction of the size of abciximab and is targeted at the same structure on the platelet surface. Clinical trials with oral glycoprotein IIb/IIIa receptor inhibitors have been disappointing, with no beneficial effects seen and even some evidence of harm.

Contraindications to aspirin

Absolute

• Active gastrointestinal ulceration
• Hypersensitivity
• Thrombocytopenia

Relative

• History of ulceration or dyspepsia
• Children under 12 years old
• Bleeding disorders
• Warfarin treatment

Edited by:

GREGORY Y H LIP
Professor of cardiovascular medicine and director, haemostasis, thrombosis and vascular biology unit, university department of medicine, City Hospital, Birmingham.

ANDREW D BLANN
Senior lecturer in medicine, haemostasis, thrombosis and vascular biology unit, university department of medicine, City Hospital, Birmingham.

Q & A: Diabetes for Pregnant

I have diabetes. How does it affect my pregnancy?

Answer: Diabetes was once a very serious medical problem during pregnancy. It continues to be an important complication of pregnancy. It continues to be an important complication of pregnancy, but today a woman can go safely through a pregnancy if she has a proper medical care, watches her diet and follows her doctor’s instructions. Using a glucometer to measure your blood sugar is a good practice.

• Glucometer – it measures the amount of sugar in a diabetic patient.

Symptoms of Diabetes are includes;

• An increase in urination
• Blurred vision
• Weight loss
• Dizziness
• Increased hunger

Why is diabetes serious in pregnancy?

Answer: Diabetes can cause several medical problems including kidney problems, eyes problems, blood problems and heart problems, such as hardening of the arteries. Any of these can be very serious to pregnant mum and to her baby as well. If diabetes is not treated, the pregnant will expose her baby to a high concentration of sugar. This is called hyperglycemia and it is not healthy for the baby.

How diabetes can be a problem to the baby?

Answer: if the pregnant have uncontrolled diabetes, the pregnant can face a significant increase in the risk of miscarriage and major abnormalities at the time of birth. The most common fetal problems are health problems, genitourinary problems and gastrointestinal problems.

How is diabetes diagnosed?

Answer: Diabetes is diagnosed with blood test called a fasting blood sugar or glucose-tolerance test.

If there is sugar in my urine, does it mean I have diabetes?

Answer: No, not necessarily, it is common for normal, pregnant, or non-diabetic person to have a small amount of sugar in their urine, called glusuria. This occurs because of changes in your sugar levels and the way sugar is handled in the kidneys or even to a pregnant.

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