1. International Project on Cardiovascular Disease in Russia
David Leon
London School of Hygiene & Tropical Medicine
Arctic University of Norway, UiT
Course on Cardiovascular Epidemiology, Samara, Russia
4 April 2016

2. Motivating Issue

3. Trends in life expectancy at birth 1965-2014

4. Mortality fluctuations mainly at working-ages

5. Mortality at working-ages in Russia drives fluctuations in life-expectancy
25-64 years
Relative mortality
[1980=100]
75-84 years
0-14 years
Source : WHO HFA
M+F combined

6. Specificity of effects by cause of death

7. Mortality from selected causes
Women, aged 45-59, Russia
Age-standardised mortality rate per 100,000
Source : WHO HFA database

8. Alcohol a key driver of fluctuations

9. Strong evidence that alcohol drives fluctuations
in male life expectancy in Russia
Source : V. Shkolnikov and E. Andreev

10. Cardiovascular Disease
Russia has one of highest cardiovascular mortality rates in the world
This accounts for half of the difference in life expectancy between Russia and the West

11. Cardiovascular mortality trends 1965-2011 in males by country
Cerebrovascular disease
Ischaemic heart disease
Age-standardised rates per 1000
Russia
Russia UK UK
Norway
Norway
Source : Shkolnikov & WHO HFA

12. Cardiovascular mortality trends 1965-2011 in females by country
Cerebrovascular disease
Ischaemic heart disease
Age-standardised rates per 1000
Russia
Russia UK UK
Norway
Norway
Source : Shkolnikov & WHO HFA

13. Fluctuations in circulatory disease mortality are closely linked to hazardous alcohol consumption

14. Source : Data provided by Evgueny Andreev

15. Challenge to view that alcohol is cardioprotective
Source : Data provided by Evgueny Andreev

16. Conducted 2003-5 Funded by the Wellcome Trust
Izhevsk Family Study
Conducted
Funded by the Wellcome Trust

17. Izhevsk, Urdmurtia Udmurtia Moscow Russian Federation
Vologda region
Arkhangelsk region
Nenets autonomous district
Republic of Komi
Kirov region
Komi-Permyatzky autonomous district
Perm region
Tver region
Yaroslavl region
Ivanovo region
Nizhny Novgorod region
Kostroma region
Vladimir region
Republic of Mariy El
Chuvash republic
Tula region
Oryol region
Rostov region
Volgograd region
Saratov region
Penza region
Tambov region
Lipetzk region
Ryazan region
Republic of Mordovia
Ulyanovsk region
Samara region
Republic of Tatarstan
Udmurt republic
Chelyabinsk region
Kurgan region
Sverdlovsk region
Yamalo-Nenetz autonomous district
Khanty-Mansi autonomous district
Tyumen region
Tomsk region
Republic of Khakasia
Kemerov region
Krasnoyarsk region
Evenki autonomous district
Taimyr (Dolgano-Nenetz) autonomous district
Irkutsk region
Ust-Ordynsky Buryat autonomous district
Chita region
Khabarovsk territory
Russian Federation
Udmurtia
Moscow 8
Udmurtia = 1.6 million; Izhevsk = 0.65 million OK

18. Izhevsk Family Study Aims
To investigate the causes of mortality among working age men (25-54 years) in a typical Russian city (Izhevsk) and in particular the role of alcohol as a factor in driving mortality 9

19. Design Case (dead men) – control (live men)
Proxy informants (living in same household)
Interviewer administered questionnaire on alcohol consumption and other characteristics especially for previous year
For cases data collected within 6-8 weeks after death
10 Changed

20. Cases and controls Cases (1750 proxies = 62% response)
Deaths of working age (25-54 years) men October 2003 to October 2005
All deaths notified by city vital statistics bureau (ZAGS)
Controls (1750 proxies= 57% response)
Live men of working age (25-54 years)
Sampled from electoral roll 11

21. Damaging patterns of alcohol consumption

22. * Specified in questionnaire as “Перепивает”
Prevalence of components of hazardous drinking in working age men in Izhevsk
Over past year
2003-5
(25-54 yrs)
2008-9
(30-59 yrs)
Spirits daily or almost every day 3% 4%
Hangover 2+ / week
Excessively drunk* 2+ / week
Non-beverage alcohol 6%
Zapoi
10%
11%
* Specified in questionnaire as “Перепивает”
N ~ 1500

23. Alcohol and mortality in Izhevsk

24. Strong association of alcohol with mortality by cause Men aged 25-54 years, Izhevsk, 2003 - 5
Cause of death
Number of deaths
Hazardous drinking
(proxy report)
OR*
(95% CI)
Circulatory disease
486
4.1
(3.2,5.3)
Acute alcohol poisoning 78
18.9
(10.7,33.3)
All causes
1446
5.5
(4.5,6.6)
* OR adjusted for age, smoking and education
Source : Leon, Shkolnikov, McKee, Kiryanov, Andreev, IJE, 2010

25. 170,000 excess male deaths per year
Impact on male deaths
Leon et al, Lancet (2007), 369 :
Hazardous drinking accounts for
43% of deaths
among working age (25-54) men in Izhevsk
170,000 excess male deaths per year
applied to Russia as a whole
Note : 2009 study from Barnaul, Siberia suggests more than half of all deaths attributable to alcohol
[Zaridze et al Lancet (2009), 373 : ]

26. Cardiovascular Disease

27. Source : Leon, Shkolnikov, McKee, Kiryanov, Andreev, IJE, 2010
Hazardous drinking and mortality from various types of circulatory disease Men aged years, Izhevsk,
Underlying cause of death
Number of deaths
Hazardous drinking
(proxy report)
OR*
(95% CI)
Alcoholic cardiomyopathy 98
15.70
(9.5,25.94)
Other cardiomyopathy 51
3.84
(2.05,7.18)
Cerebrovascular disease 90
2.05
(1.24,3.40)
Other circulatory disease 28
3.43
(1.51,7.81)
Ischaemic heart disease
219
3.04
(2.17,4.24)
* OR adjusted for age, smoking and education
Source : Leon, Shkolnikov, McKee, Kiryanov, Andreev, IJE, 2010

28. Other factors (not only alcohol) are also important in explaining why Russian CVD mortality is so high

29. Smoking Important but does not explain fluctuations

30. Trends of adult smoking rates in Russia, 1992–2009
Source : Lunze K &Migliorini L. BMC Public Health 2013;13:64

31. Paradoxical lipid profile relative to other countries
Prevalence of raised total cholesterol not high
Levels of LDL (“bad”) cholesterol tend to be average or below average
Levels of HDL (“good”) cholesterol tend to be above average
NB : national data not available
NB : statin use very low

32. Hypertension High rates in Russia compared to other European countries
Poor rates of control
Likely to be an important factor
NB : published national data poorly documented and of uncertain quality

33. Classic risk factors do not explain international differences

34. Two simple questions
What is the explanation for Russia’s very high and fluctuating cardiovascular mortality ?
What can be done about it ?

35. Arctic University of Norway, UiT Norwegian Ministry of Health
International Project on Cardiovsacular Disease in Russia (IPCDR)
Arctic University of Norway, UiT
Norwegian Ministry of Health

36. Institute of Internal Medicine
SBRAMS, Novosibirsk, Russia
Cardiovascular disease in Russia: strengthening evidence about causes, mechanisms, prevention and treatment
Finland
Max Planck Institute for Demographic Research

37. Location of study sites and collaborators
Tromso
Oulu
Arkhangelsk
Kazan
Novosibirsk
Moscow
Rostock
London

38. Main aims of study
To understand and quantify for the first time the likely reasons for the extremely high rates of premature mortality from cardiovascular disease in Russia
To generate new knowledge about the mechanisms underlying the impact of alcohol on cardiovascular disease
To effectively communicate findings so as to improve primary and secondary prevention of cardiovascular disease in Russia

39. Four themes
Theme A: Data synthesis : levels and trends in cardiovascular disease and associated risk factors from existing studies/surveys Theme B: Aetiology : CVD profile of the Russian population Theme C: Importance of primary and secondary prevention – role of the health sector Theme D: Validity and comparability of cause of death

40. Theme D – Validity and comparability of cause of death in Russia and Norway

41. Percentage of adult deaths by certifying specialist, Russia, 2000-10
Sex and age
Pathologist or forensic expert
Physician or paramedic
Males, 15-59
74.7
25.3
Males, 60+
28.7
71.3
Females, 15-59
61.5
38.5
Females, 60+
19.3
80.7
Source : Andreev et al paper in preparation

42. Huge regional variation in Russia in autopsy rates

43. Source : Andreev et al paper in preparation
Percentage of deaths from non-violent causes certified by a pathologist in regions of Russia in
Source : Andreev et al paper in preparation

44. Theme C – Contribution of the health sector

45. Treatment of acute myocardial infarction study

46. 15 Study centers Ufa Perm Archangelsk Tver Khanti-Mansyisk Kazan
Bryansk
Perm
Khanti-Mansyisk
Kazan
Belgorod
Tumen
Saratov
Samara
Rostov-on-Don
Ufa
Kemerovo
Irkutsk
Barnaul

47. Theme B : Aetiology - CVD profile of Russian population
Cross-sectional studies in Arkhangelsk and Novosibirsk
Population-based random samples
men and women aged years
attention given to reducing selection bias
N=2250 in each city
Additional sample heavy alcohol drinkers from medical facility (N=250 in each city)
Main field work started November 2015 and will last for ~24 months

48. Cardiovascular phenotypes Biomarker/proxy measure
Source
Biomarker/proxy measure
Atherosclerosis
Questionnaire
Previous MI
ECG
Evidence previous MI
Carotid ultrasound
Carotid IMT, plaque
Cardiac remodelling
Blood
NT-pro BNP, HsTnI, hsTnT
Echocardiography
Myocardial function and size
Arrhythmia
ECG, Actiheart
Heart rate variability
Vascular dysfunction
Vicorder
Pulse-wave velocity

49. Cutting edge -omic and molecular approaches

50. Serum NMR metabolomics
Highly standardised and reproducible platform for 117 primary and 99 derived measures of specific molecular entities (now >100,000 individuals assayed)
Nature Genetics 44, 269, 2012
How are alcohol and CVD phenotypes related to 14 lipoprotein subclasses ?
Identifying markers of intermediate metabolism associated with CVD phenotypes

51. Associations : Analytic framework
Studies in
other countries
eg Tromsø 7
Endogenous exposures :
a priori CVD risk biomarkers
(including lipoprotein NMR profile)
Socio-demographic +
exogenous exposures
CVD
phenotypes
Metabolic profile
Microbiome

52. Improving recruitment

54. Project launch meeting
Moscow 2-3 June 2014

55. What will the project produce ?
New knowledge about balance of factors responsible for high CVD mortality and underlying mechanisms (scientific publications) that will be of worldwide interest
Synthesis of results including key implications for prevention and treatment strategies actively communicated to stakeholders in Russia
Creation of data repository and biobank resource that will be accessible to the international scientific community
Research capacity development in field of epidemiology
Strengthening of international scientific links
Improve understanding and trust between countries

56. Спасибо Thank you