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Dispositional optimism and all-cause and cardiovascular mortality in a prospective cohort of elderly Dutch men and women
Preventive Cardiology
cation to measure Lp-PLA2 with the CRP is risk-stratifying intermediate risk patients and possibly low-risk individuals with a family history of premature CHD. MR
Abstracts Lipoprotein-Associated Phospholipase A2 Adds to Risk Prediction of Incident Coronary Events by C-Reactive Protein in Apparently Healthy Middle-Aged Men From the General Population
Dispositional Optimism and All-Cause and Cardiovascular Mortality in a Prospective Cohort of Elderly Dutch Men and Women
Koenig W, Khuseyinova N, Löwel H, et al. Circulation 2004;110: 1903– 8.
Giltay EJ, Geleijinse JM, Zitman FG, et al. Arch Gen Psychiatry 2004;61:1126 –35.
Study Question: Lipoprotein-associated lipase A2 (Lp-PLA2), an enzyme produced by monocytes and macrophages, is located in the arterial wall and serum. Does it predict risk of future coronary events in apparently healthy men? Methods: Plasma concentrations of Lp-PLA2 were determined by ELISA in 934 apparently healthy men aged 45– 64 years participating in the MONICA (MONItoring of trends and determinants in CArdiovascular disease) study. Samples were collected from the general population in 1984 and followed until 1998. During this period, 97 men experienced a coronary event diagnosed according to the MONICA protocol. Results: Average age was 54 years, BMI was 27.6 kg/m2, BP 137/85 mm Hg, C-reactive protein (CRP) 1.62 mg/L, cholesterol 245 g/dL, HDL-C 51 mg/dL, 31% were smokers, and 35% were physically active. Mean Lp-PLA2 was 266⫾84 ng/L. Baseline levels of Lp-PLA2 were higher in subjects who experienced an event than in event-free subjects (295⫾113 vs. 263⫾79 ng/mL; p⬍0.01). Lp-PLA2 was positively correlated with total cholesterol (R⫽0.30; p⬍0.0001) and age (R⫽0.12; p⫽0.001), was only slightly correlated with HDL-C (R⫽0.09; p⫽0.005) and C-reactive protein R⫽0.06; p⫽0.06), but was not correlated with BMI or blood pressure. In a Cox model, a 1-SD increase in Lp-PLA2 was associated with risk of future coronary events (HR [hazard ratio] 1.37; 95% CI 1.16 –1.62). After controlling for potential confounders, the HR was attenuated but remained statistically significant (HR 1.23; 95% CI 1.02– 1.47). Further inclusion of CRP in the model did not appreciably affect its predictive ability (HR 1.21; 95% CI 1.01–1.45). There was an additive effect of CRP ⬎3 mg/dL. Conclusions: Elevated levels of Lp-PLA2 appeared to be predictive of future coronary events in apparently healthy middle-aged men with moderately elevated total cholesterol, independent of CRP. This suggests that Lp-PLA2 and CRP may be additive in their ability to predict risk of coronary heart disease. Perspective: Lp-PLA2 has been shown to be an independent predictor of risk for coronary events in other studies including WOSCOPS and ARIC. Its role as a marker is reasonably established, and in the future may be a therapeutic target as the product of its effect on lipoprotein phospholipids may contribute to coronary events. Like the CRP, it is a marker of increased risk but has limited ability to predict risk in an individual patient. It is available for clinical use. The indi-
Study Question: Depression is a risk factor for cardiovascular mortality. Does dispositional optimism (expectancy that good things will happen rather than bad) reduce all-cause and cardiovascular mortality in elderly men and women? Methods: A prospective population-based cohort study in the Netherlands (Arnhem Elderly Study) was conducted in the general community. Elderly subjects aged 65– 85 years (999 men and women) completed the 30-item validated Dutch Scale of Subjective Well-Being for Older Persons, with five subscales: health, self-respect, morale, optimism, and contacts. A total of 941 subjects (466 men and 475 women) had complete dispositional optimism data, and these subjects were divided into quartiles. The main outcome measure was the number of deaths during the follow-up period. Results: Mean age was 74.5 years. The median optimism score was 12.9⫾4.8 (range 0 –20) and did not differ by gender. During the follow-up period of 9.1 years (1991– 2001), there were 397 deaths. Compared with subjects with a high level of pessimism, those reporting a high level of optimism had an age- and gender-adjusted hazard ratio (HR) of 0.55 (95%CI, 0.42– 0.74; upper vs. lower quartile) for all-cause mortality. For cardiovascular mortality, the HR was 0.23 (95%CI, 0.10 – 0.55) when adjusted for age, gender, chronic disease, education, smoking, alcohol consumption, history of cardiovascular disease or hypertension, BMI, and total cholesterol level. Protective trend relationships were observed between the level of optimism and all-cause and cardiovascular mortality (p⬍0.001 and p⫽0.001 for trend, respectively). Interaction with gender (p⫽0.04) supported a stronger protective effect of optimism in men than in women for all-cause mortality but not for cardiovascular mortality. Conclusions: The results provide support for a graded and independent protective relationship between dispositional optimism and all-cause mortality in old age. Prevention of cardiovascular mortality accounted for much of the effect. Perspective: Ever increasing scientific evidence shows that it is better to be happy, spiritual (not necessarily religious), forgiving, and now optimistic. The nearly 80% risk reduction for cardiovascular mortality attributable to optimism is a message for our patients and ourselves. “So now, Mr. Pennyschmidt, the good news is that your LDL cholesterol is low and your HDL cholesterol is high, but the bad news is that you’re a pessimist and you need to work on it.” MR
ACC CURRENT JOURNAL REVIEW February 2005
17
cation to measure Lp-PLA2 with the CRP is risk-stratifying intermediate risk patients and possibly low-risk individuals with a family history of premature CHD. MR
Abstracts Lipoprotein-Associated Phospholipase A2 Adds to Risk Prediction of Incident Coronary Events by C-Reactive Protein in Apparently Healthy Middle-Aged Men From the General Population
Dispositional Optimism and All-Cause and Cardiovascular Mortality in a Prospective Cohort of Elderly Dutch Men and Women
Koenig W, Khuseyinova N, Löwel H, et al. Circulation 2004;110: 1903– 8.
Giltay EJ, Geleijinse JM, Zitman FG, et al. Arch Gen Psychiatry 2004;61:1126 –35.
Study Question: Lipoprotein-associated lipase A2 (Lp-PLA2), an enzyme produced by monocytes and macrophages, is located in the arterial wall and serum. Does it predict risk of future coronary events in apparently healthy men? Methods: Plasma concentrations of Lp-PLA2 were determined by ELISA in 934 apparently healthy men aged 45– 64 years participating in the MONICA (MONItoring of trends and determinants in CArdiovascular disease) study. Samples were collected from the general population in 1984 and followed until 1998. During this period, 97 men experienced a coronary event diagnosed according to the MONICA protocol. Results: Average age was 54 years, BMI was 27.6 kg/m2, BP 137/85 mm Hg, C-reactive protein (CRP) 1.62 mg/L, cholesterol 245 g/dL, HDL-C 51 mg/dL, 31% were smokers, and 35% were physically active. Mean Lp-PLA2 was 266⫾84 ng/L. Baseline levels of Lp-PLA2 were higher in subjects who experienced an event than in event-free subjects (295⫾113 vs. 263⫾79 ng/mL; p⬍0.01). Lp-PLA2 was positively correlated with total cholesterol (R⫽0.30; p⬍0.0001) and age (R⫽0.12; p⫽0.001), was only slightly correlated with HDL-C (R⫽0.09; p⫽0.005) and C-reactive protein R⫽0.06; p⫽0.06), but was not correlated with BMI or blood pressure. In a Cox model, a 1-SD increase in Lp-PLA2 was associated with risk of future coronary events (HR [hazard ratio] 1.37; 95% CI 1.16 –1.62). After controlling for potential confounders, the HR was attenuated but remained statistically significant (HR 1.23; 95% CI 1.02– 1.47). Further inclusion of CRP in the model did not appreciably affect its predictive ability (HR 1.21; 95% CI 1.01–1.45). There was an additive effect of CRP ⬎3 mg/dL. Conclusions: Elevated levels of Lp-PLA2 appeared to be predictive of future coronary events in apparently healthy middle-aged men with moderately elevated total cholesterol, independent of CRP. This suggests that Lp-PLA2 and CRP may be additive in their ability to predict risk of coronary heart disease. Perspective: Lp-PLA2 has been shown to be an independent predictor of risk for coronary events in other studies including WOSCOPS and ARIC. Its role as a marker is reasonably established, and in the future may be a therapeutic target as the product of its effect on lipoprotein phospholipids may contribute to coronary events. Like the CRP, it is a marker of increased risk but has limited ability to predict risk in an individual patient. It is available for clinical use. The indi-
Study Question: Depression is a risk factor for cardiovascular mortality. Does dispositional optimism (expectancy that good things will happen rather than bad) reduce all-cause and cardiovascular mortality in elderly men and women? Methods: A prospective population-based cohort study in the Netherlands (Arnhem Elderly Study) was conducted in the general community. Elderly subjects aged 65– 85 years (999 men and women) completed the 30-item validated Dutch Scale of Subjective Well-Being for Older Persons, with five subscales: health, self-respect, morale, optimism, and contacts. A total of 941 subjects (466 men and 475 women) had complete dispositional optimism data, and these subjects were divided into quartiles. The main outcome measure was the number of deaths during the follow-up period. Results: Mean age was 74.5 years. The median optimism score was 12.9⫾4.8 (range 0 –20) and did not differ by gender. During the follow-up period of 9.1 years (1991– 2001), there were 397 deaths. Compared with subjects with a high level of pessimism, those reporting a high level of optimism had an age- and gender-adjusted hazard ratio (HR) of 0.55 (95%CI, 0.42– 0.74; upper vs. lower quartile) for all-cause mortality. For cardiovascular mortality, the HR was 0.23 (95%CI, 0.10 – 0.55) when adjusted for age, gender, chronic disease, education, smoking, alcohol consumption, history of cardiovascular disease or hypertension, BMI, and total cholesterol level. Protective trend relationships were observed between the level of optimism and all-cause and cardiovascular mortality (p⬍0.001 and p⫽0.001 for trend, respectively). Interaction with gender (p⫽0.04) supported a stronger protective effect of optimism in men than in women for all-cause mortality but not for cardiovascular mortality. Conclusions: The results provide support for a graded and independent protective relationship between dispositional optimism and all-cause mortality in old age. Prevention of cardiovascular mortality accounted for much of the effect. Perspective: Ever increasing scientific evidence shows that it is better to be happy, spiritual (not necessarily religious), forgiving, and now optimistic. The nearly 80% risk reduction for cardiovascular mortality attributable to optimism is a message for our patients and ourselves. “So now, Mr. Pennyschmidt, the good news is that your LDL cholesterol is low and your HDL cholesterol is high, but the bad news is that you’re a pessimist and you need to work on it.” MR
ACC CURRENT JOURNAL REVIEW February 2005
17