The Risk of Both Stroke and Coronary Heart Disease (CHD) Nearly Double

LONDON and PHILADELPHIA, Feb. 8 /PRNewswire-FirstCall/ -- Results of a newly published study in the journal "Circulation" show that the activity of an enzyme - lipoprotein-associated phospholipase A2 (Lp-PLA2) - significantly predicts ischemic stroke and coronary heart disease (CHD) in adults independent of other cardiovascular risk factors, including the inflammatory protein C-reactive protein (CRP) and cholesterol, according to an analysis of the Rotterdam Study that appears in the February 8, 2005 issue(i). "Circulation" is the peer-reviewed journal of the American Heart Association (AHA) devoted exclusively to covering cardiovascular disease.

"The Rotterdam Study is the first prospective population study to demonstrate that Lp-PLA2 activity is a significant predictor of ischemic stroke. Additionally, the study provides further evidence that Lp-PLA2 is a significant predictor of coronary heart disease. Importantly, the Lp-PLA2 associations with stroke and CHD were independent of traditional cardiovascular risk factors and CRP," reports lead author Hok-Hay S. Oei, MD, Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.

Rotterdam participants with the highest levels of Lp-PLA2 activity had almost double the risk of coronary heart disease and ischemic stroke - the blockage of a brain blood vessel - compared with those with the lowest levels of Lp-PLA2 activity.

"The Rotterdam analysis indicates that Lp-PLA2 activity may be useful as a predictor of atherosclerotic vascular disease burden in the general population. Because of the role of Lp-PLA2 in the biology of cardiovascular disease, it has significant potential as a target for drug development," said Lawson Macartney, Senior Vice-President, Cardiovascular and Metabolic Medicine Development Center, GlaxoSmithKline ("GSK"). GSK is investigating several Lp-PLA2 activity inhibitors in clinical trials to determine the role they may play in further reducing the risk of cardiovascular disease.

Lp-PLA2 Activity Independently Predicts Ischemic Stroke and Coronary Heart Disease

In the Rotterdam analysis, the associations of Lp-PLA2 with ischemic stroke and CHD were statistically significant and independent of other cardiovascular risk factors including age, sex, body mass index (BMI), systolic blood pressure, cholesterol levels, diabetes, smoking, CRP, alcohol consumption, white cell count, and cholesterol-lowering medications.

When participants were placed into four groups based on their Lp-PLA2 activity, those with the highest Lp-PLA2 activity, group four, had a 95 percent greater risk of ischemic stroke compared with those with the lowest Lp-PLA2 activity, group one, after adjusting for cardiovascular risk factors.

Similarly, the risk for coronary heart disease in group four (those with the highest Lp-PLA2 activity) had a 96 percent greater risk compared with that of group one (those with the lowest Lp-PLA2 activity).

"The significant and independent association between Lp-PLA2 activity and both stroke and coronary heart disease suggests that the enzyme, although carried on low-density lipoprotein (LDL-C, or 'bad') cholesterol, may convey a different cardiovascular risk than that from cholesterol. Lp-PLA2 has pro- inflammatory properties and inflammation is involved in atherosclerosis and plaque rupture, which contribute to cardiovascular disease," explains Albert Hofman, MD, PhD, Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam.

About Lp-PLA2 Activity and Atherosclerosis

Lp-PLA2 primarily circulates in the blood attached to LDL-C. Lp-PLA2 acts on oxidized forms of lipids and its activity generates several by-products that promote inflammation in atherosclerotic plaque, which develops as fatty deposits within arterial walls(ii). Atherosclerosis underlies heart attacks and most strokes(iii).

Cardiovascular disease accounts for nearly 50 percent of all deaths in Europe(iv). Despite the use of cholesterol-lowering drugs, such as statins, and other agents, millions of patients remain at risk for heart disease. Heart disease and stroke kill some 17 million people each year, almost a third of all deaths globally, the World Health Organization (WHO) reports(v). By 2020, heart disease and stroke will become the leading cause of both death and disability worldwide, accounting for more than 20 million deaths annually.

About The Rotterdam Study

The Rotterdam Study is an ongoing population-based observational study of 7,983 men and women, representing 78 percent of the inhabitants age 55 and older of a suburb of Rotterdam, who were invited to enroll from 1990 to 1993. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam.

The Rotterdam Study analysis by Oei and his colleagues compared all cases of CHD (308 participants), all cases of ischemic stroke (108 participants) and a subgroup of randomly selected participants (1,822) in a case-cohort study design. The participants were age 55 years and older (average age 70 years). The investigators defined coronary heart disease as including the occurrence of a fatal or non-fatal heart attack, other forms of acute or chronic ischemic heart disease, sudden cardiac death and deaths due to ventricular fibrillation or congestive heart failure. Only strokes that met the criteria of definite or probable ischemic stroke were included as cases. An unrestricted grant from GlaxoSmithKline supported this analysis of the Rotterdam data.

About GlaxoSmithKline

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information visit http://www.gsk.com/.

For inquiries regarding the Rotterdam study and other GSK activities, please contact:

Inquiries: UK Media inquiries: Philip Thomson (020) 8047 5502 David Mawdsley (020) 8047 5502 Chris Hunter-Ward (020) 8047 5502 US Media inquiries: Rick Koenig (610) 270 5546 European Analyst/Investor inquiries: Duncan Learmouth (020) 8047 5540 Anita Kidgell (020) 8047 5542 US Analyst/ Investor inquiries: Frank Murdolo (215) 751 7002 Tom Curry (215) 751 5419 References (i) Oei, van der Meer, Hofman, et al. Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: The Rotterdam Study. Circulation 111:570-575, 2005. (ii) Iribarren, Carlos, et al. Association of Lipoprotein-Associated Phospholipase A2 Mass and Activity With Calcified Coronary Plaque in Young Adults: The CARDIA Study. Arterioscler Thromb Vasc Biol. 25:216-221, 2005. (iii) American Heart Association. "Atherosclerosis," 2005. (iv) American Heart Association. "International Cardiovascular Disease Statistics" 2004. (v) WHO publishes definitive atlas on global heart disease and stroke epidemic, World Health Organization news release, Sept. 23, 2004.