IJE Advance Access originally published online on March 31, 2006
International Journal of Epidemiology 2006 35(4):1025-1033; doi:10.1093/ije/dyl058
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Published by Oxford University Press on behalf of the International Epidemiological Association
Article |
The impact of cardiovascular risk factors on the age-related excess risk of coronary heart disease
Asia Pacific Cohort Studies Collaboration*Correspondence to: Rachel Huxley, Asia Pacific Cohort Studies Collaboration Secretariat, The George Institute for International Health, PO Box M201, Missenden Road, Sydney NSW 2050, Australia. E-mail: rhuxley{at}thegeorgeinstitute.org
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Purpose Differences in cardiovascular risk factor levels have been suggested to contribute to the age-related excess risk of coronary heart disease (CHD). The aim of this study was to reliably quantify these contributions using a large prospective dataset.
Methods We carried out an individual participant data meta-analysis of 41 cohort studies (n = 582 134) from Asia, and Australia and New Zealand. Cox models were used to estimate hazard ratios for coronary death, comparing individuals aged 55–64, 65–74, and 
5 yrs with those aged <55 yrs. Adjustments were made for coronary risk factors to quantify their contributions to the age differential.
Results During 4.1 million person-years of follow-up, there were 2915 deaths from CHD. The risk of CHD increased substantially with age in all groups, especially in women. Differences in cardiovascular risk factors explained between one-quarter to one-third of the age-related excess of CHD in men and one-half of that in women. Systolic blood pressure was the chief contributor to the excess risk in all groups.
Conclusions Systolic blood pressure was the most important modifiable risk factor contributing to the excess CHD risk that occurs with aging in men and women, but in comparison with the effects of age itself, the effects of blood pressure are small.
Keywords Aging, cardiovascular risk factors, CHD, sex
Accepted 10 March 2006
Currently, there are 600 million people worldwide aged 60 yrs or over. This figure is expected to double by 2025, reaching 2 billion by 2050, and most of them will be living in countries of the Asia-Pacific.1 It is well established that the risk of dying from coronary heart disease (CHD) increases substantially with age, in both men and women2,3—but it remains unclear how much of this increase is avoidable. Increases in levels of risk factors, in particular total cholesterol and blood pressure, have been suggested to explain a substantial amount of the age-related increase in CHD,4 but a lack of sufficient prospective data has previously precluded reliable quantification of the contributions of risk factors to the excess CHD mortality in populations of the Asia-Pacific region. Considering the unprecedented rate at which populations are aging worldwide, and that CHD is one of the leading causes of death in individuals >60 yrs,5 such information could have a crucial role in reducing the excess number of premature deaths from CHD in middle and old age.
The Asia Pacific Cohort Studies Collaboration (APCSC) comprises a large number of prospective cohort studies in the region and was established primarily to provide reliable evidence about the effects of a variety of modifiable risk factors, including blood pressure, lipids, body mass index (BMI) and diabetes, on the risks of cardiovascular diseases and other common causes of death among populations in this region.6 This paper uses data from the APCSC (i) to report the cross-sectional mean levels of classical risk factors, separately for men and women, by age group and (ii) to quantify to what extent variations in levels of risk factors contribute to the age-related increase in CHD mortality.
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Methods |
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Participating studies
The APCSC is an overview conducted by the principal investigators of longitudinal observational studies conducted in the region. Details of the methods of study identification and data collection are described elsewhere.6–10 Briefly, studies were eligible for inclusion in the APCSC if they were conducted prospectively in a population from the Asia-Pacific region, recorded age, sex, and blood pressure at baseline and vital status at the end of the follow-up, and continued the follow-up for at least 5000 person-years. Studies were not eligible if entry was dependent on having a particular medical condition or risk factor. To examine regional differences, cohorts were classified as: Asian if their participants were recruited from China, Hong Kong, Japan, Korea, or Taiwan; or Australia and New Zealand (ANZ) if their participants were recruited from Australia or New Zealand. All datasets were centrally checked for consistency, and where necessary, further details were sought from collaborating investigators. These studies were performed in accordance with the Declaration of Helsinki.
Variables measured at baseline
In most studies, blood pressure was measured at rest in the seated position using a standard mercury sphygmomanometer7 and total cholesterol was generally measured from fasting serum.8 Baseline BMI was defined as weight (kg) divided by height (m2).9 Smoking status was recorded as either current smoker or non-smoker of cigarettes. Diabetic status was determined on the basis of either a reported history of diabetes at baseline or using a fasting venous blood sample10 according to the WHO definition of diabetes (i.e. fasting glucose 7.0 mmol/l or 2 h post-glucose load 11.1 mmol/l). Detailed information regarding the measurement and recording of these variables is given elsewhere.5–10
Outcomes
All outcomes were classified according to the ninth revision of the International Classification of Diseases (ICD-9). Each death was ascribed to its underlying cause, as reported on the death certificate. The end point considered in this paper is death from CHD (ICD 410–414).
Statistical methods
All analyses were based on individual participant data, were region-specific and sex-specific, were restricted to participants aged >20 yrs at the time of the baseline survey, and to studies that included both men and women. For the cross-sectional analyses of mean levels of risk factors, individuals were categorized into 10 yr age bands. For the survival analyses, to have a sufficient number of events in each category to maximize precision, individuals were divided into only four groups according to age at risk (i.e. age at time of event for those with a positive outcome), <55; 55–64; 65–74; 75+ yrs. Hazard ratios (HRs) and 95% confidence intervals for fatal CHD within each age-at-risk group were estimated using time-dependent Cox proportional hazard models, stratified by study. All the results were first unadjusted, then adjusted for each single risk factor in turn, and finally adjusted for all risk factors together. The percentage excess risk of CHD in each of the age groups: 55–64; 65–74; 75 yrs, compared with <55 yrs, that was due to differences in risk factor levels was estimated by 100 [(HRU – HRA)/(HRU – 1)]% where HRU and HRA are, respectively, the HRs for CHD comparing the selected age group with <55 yrs unadjusted, and after (further) adjustment for other risk factors.
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Data available
The characteristics of studies within the APCSC, and the mean values of risk factors at baseline in men and women, separately for Asia and ANZ cohorts, are shown in Tables 1 and 2. In both Asia and ANZ, men had higher mean levels of systolic blood pressure, BMI, triglycerides, glucose, and a substantially higher rate of cigarette smoking compared with women. The highest values were in men from ANZ, with the exception of the prevalence of cigarette smoking that was much greater in Asian men compared with men from ANZ (59% vs 23%). Partly owing to the large sample size, the differences in mean values between men and women were all highly significant (P < 0.001).
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Age-specific differences in levels of risk factors
The mean levels of risk factors in men and women, by region, are shown in Figures 1a–h. The most striking findings relate to differences in triglyceride levels by age and sex (Figure 1a). Women had consistently lower triglyceride levels than men up until the age of 60 yrs. However, the difference was markedly reduced with age, as a consequence of mean triglyceride levels becoming increasingly higher among successive age groups in women from both Asia and ANZ. In Asian men, triglyceride levels tend to decrease with age, but the reverse was true for men from ANZ, in whom levels tend to be higher in mid-life and remain high thereafter.
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At all ages, the mean cholesterol level among Asians was consistently lower than that among populations from ANZ (Figure 1b). Within both Asia and ANZ, mean total cholesterol levels tend to be higher with successive age groups up to 55 yrs in both men and women, after which, the levels began to gradually decline with age, with the exception of ANZ women, in whom levels tend to increase further with age. At all ages, and in both regions, the mean level of high-protein lipoprotein cholesterol (HDL-cholesterol) was higher among women than among men, and remained relatively constant with age, with the notable exception of Asian men in whom HDL-cholesterol levels tend to increase with age (Figure 1c). Cigarette smoking rates were the highest by a substantial margin among Asian men where
60%, under the age of 65 yrs, were current smokers (Figure 1d). The prevalence of cigarette smoking decreased with age in all groups except in Asian women for whom levels, although low, tend to increase with age.
Mean levels of systolic blood pressure increased linearly with each decade of life in both men and women to a similar extent, in both Asian and ANZ cohorts, but were consistently lower among Asians (Figure 1e). The prevalence of diabetes showed a similar increase with age (Figure 1f). Mean levels of BMI were consistently lower in Asian studies, but levels tend to increase with age within all cohorts, peaking at 50 yrs in Asians and 60 yrs in individuals from ANZ, after which the mean level of BMI declined with each successive decade (Figure 1h).
Differences in levels of risk factors and risk of CHD
During 4.1 million person-years of follow-up, there were 2915 (926 women) deaths from CHD. Tables 3 and 4 show the rates of fatal CHD, and the impact of aging on the unadjusted HRs for fatal CHD, separately for men and women in Asia and ANZ. As anticipated, age substantially increased the risk of CHD in all groups, particularly among women from ANZ, where there was an 200-fold increase in CHD risk among women aged >75 yrs compared with women aged <55 yrs. Tests for heterogeneity indicated that aging had a significantly greater detrimental impact on women compared with men in both regions. There was also evidence of regional differences, with the effect of aging being greater in men (P = 0.039) and women (P = 0.0004) from ANZ compared with their Asian peers.
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Cardiovascular risk factors explained approximately one-quarter and one-third of the excess CHD risk associated with aging among men from ANZ and Asia, respectively (Figures 2a and b). In particular, higher systolic blood pressure was the chief contributor to the excess risk, and became increasingly more important among successive age categories. Among ANZ men, a modest amount of the age-related excess CHD risk was explained by higher levels of total cholesterol and triglycerides that were substantially greater than that among their Asian counterparts. In contrast, in Asians, higher levels of lipids and diabetes explained only a small amount of the excess CHD risk associated with aging.
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In women, cardiovascular risk factors explained approximately one-half of the age-related excess CHD risk. (Figures 2a and b). As with men, higher systolic blood pressure was by far the most significant contributor to this excess risk, especially in the older age groups. In women from ANZ, higher levels of triglycerides and total cholesterol contributed substantially to the age-related risk, much more so than in Asian women. An additional small amount of the excess risk among all women was explained by a greater prevalence of diabetes among older women. The remaining risk factors BMI, cigarette smoking, and HDL-cholesterol did not contribute to the excess risk of CHD among either men or women; hence, their exclusion from Figure 2.
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Conclusions |
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Among men and women from both Asia and ANZ, systolic blood pressure was the most important, modifiable component of the increased risk of CHD associated with aging. In addition, in ANZ, triglyceride and total cholesterol levels also contributed to the age-related excess risk; to a much greater extent in women. In contrast, a higher prevalence of diabetes in older people explained more of the age-related excess risk in Asian populations than did lipids.
These findings are largely compatible with those reported by Jousilhati et al.4 in a prospective cohort of nearly 15 000 Finnish individuals aged 25–64 yrs. They reported that increases in total cholesterol, blood pressure, and diabetes were the risk factors most strongly associated with the age-related increase in CHD in all individuals, but to a greater extent in women (35% in men vs 64% in women). Our findings are also compatible with a large body of evidence, which indicates that the prevalences of hypertension and diabetes increase with age.12,13 By comparison, the relationship between total cholesterol level and age is more complex. Observations from prospective studies report both total and low-density cholesterol levels increase with age in young or middle-aged adults14,15 but decline after the age of 65 yrs; 16,17 consistent with our current findings. In women, the increase in total cholesterol level is widely considered to coincide with the onset of menopause, with the subsequent changes in hormone levels considered to promote a more atherogenic lipid profile.18,19 The subsequent decline in total cholesterol level with age that we report here is unlikely to be due to survivor bias because it has also been observed prospectively.20,21
Consistent with previous reports14,15, the mean level of HDL-cholesterol was higher among women than among men, and remained relatively constant with age, with the notable exception of Asian men, in whom levels tend to increase with age. Findings from cross-sectional studies indicate that HDL-cholesterol levels remain relatively stable with age, as we report here, whereas prospective studies indicate a decline with age. The finding of an increase in HDL-cholesterol level with age among Asian men suggests a birth cohort effect; smoking is associated with lower HDL-cholesterol levels, and since smoking has only recently become popular in Asia, low prevalences of smoking in Asian men aged >60 yrs may account for the higher HDL-cholesterol levels at older ages.
There are several potential explanations as to why the combined risk factors accounted for more of the age-related excess CHD risk in women than in men. The first relates to the age-related differences in the mean levels of risk factors between the sexes, the most striking of which was the increase in triglyceride levels in women, especially those from ANZ. The greater age-related increase in BMI that occurs, particularly in ANZ women, may partially explain the larger increase in mean levels of triglycerides and total cholesterol among these women compared with that among Asian women. A second explanation relates to earlier findings of a sex interaction between blood pressure and fatal CHD. Previously, we reported that a 10 mm Hg increase in systolic blood pressure was associated with a 35% increased risk of fatal CHD in women compared with an increase of only 20% among men.22 This sex interaction may partially explain why, despite similar increases in blood pressure with age, adjustment for systolic blood pressure explained considerably more of the excess CHD risk with aging in women compared with men.
The cross-sectional nature of the analyses examining the mean levels of risk factors within each age group is one of the main limitations of this study, as it means that the successive age categories comprises different birth cohorts. Hence, age-related changes in risk factor levels may be modified by secular trends in the population, which impact on lifestyle choices that in turn influence the levels of the majority of risk factors examined. For example, diet23 and rates of cigarette smoking,24 particularly in Asia, have changed substantially over the last 50 yrs, which consequently would affect, among other risk factors, the patterns across the age groups of diabetes and cigarette smoking. Furthermore, it is possible that the explanatory potential of smoking and diabetes may have been underestimated, as it was not possible to examine the impact of their cumulative exposure on CHD mortality. For example, decades of exposure to cigarette smoking would undoubtedly have resulted in higher relative risks among elderly smokers compared with younger individuals. Unfortunately, the APCSC does not contain information on age of commencement of smoking or on pack years smoked, and similarly, we do not have this information for diabetes.
‘Survival bias’, whereby individuals with the lowest levels of risk factors survive into old age, may also have impacted on the cross-sectional analyses. Random and systematic error in the measurement of these classical risk factors, in particular blood pressure and lipids, is likely to have been substantial, and will have resulted in the underestimation of their contribution to the age-related excess risk of CHD. In addition, owing to a lack of data on the use of prescribed medication in study participants, we were unable to evaluate the impact of any treatment differences on age-related CHD risk. We were also reliant upon individual study case ascertainment; hence, the accuracy of cause of death may have varied across the studies and across time. Further limitations of this study include those that are common to most observational studies, such as selection bias through the inclusion of several occupational cohorts, which are not representative of the general population. Residual confounding from unmeasured risk factors, such as fibrinogen and C-reactive protein, may also have been present, although it is unlikely that their inclusion into the analyses would have significantly altered the current findings.
In summary, systolic blood pressure was the most important and modifiable risk factor explaining some of the excess CHD risk that occurs with aging. In comparison with the effects of age itself; however, the effects of blood pressure are small. For example, for an Asian woman aged between 65 and 75 yrs to be at the same level of risk as she was 10 yrs previously, her blood pressure would have to be reduced by more than 50 mm Hg. Although this estimate is larger than that of a 30 mm Hg reduction obtained from the Prospective Studies Collaboration,25 this latter study did not report the results separately for men and women, or by region, which could account, at least in part, for the discrepancy. Hence, strategies aimed at lowering blood pressure (as well as other risk factors, particularly total cholesterol) would do much to offset the large number of premature coronary deaths that occur among aging populations. It also lends support to the recent idea that prescribing all individuals over the age of 55 yrs a ‘polypill’ (a combined antihypertensive and lipid lowering medication) irrespective of their risk factors levels would prevent a substantial number of cardiovascular events.26 Treating an individual's overall level of risk, of which age is by far the most important component, rather than focusing on individual risk factor levels, may well be the key to reducing the growing burden of cardiovascular disease that is becoming increasingly evident in most populations.
KEY MESSAGES
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Writing Committee: Rachel Huxley, Federica Barzi, TH Lam, Carlene MM Lawes, Jean Woo Wong, Mark Woodward
Executive Committee: M Woodward, X Fang, DF Gu, Y Imai, TH Lam, WH Pan, A Rodgers, I Suh, HJ Sun, H Ueshima
Statistical Analyses: F Barzi, M Woodward.
Participating studies and principal collaborators in APCSC: Aito Town: A Okayama, H Ueshima, H Maegawa; Akabane: N Aoki, M Nakamura, N Kubo, T Yamada; Anzhen 02: ZS Wu; Anzhen: CH Yao, ZS Wu; Australian Longitudinal Study of Aging: G Andrews; Australian National Heart Foundation: TA Welborn; Beijing Aging: Z Tang; Beijing Steelworkers: LS Liu, JX Xie; Blood Donors' Health: R Norton, S Ameratunga, S MacMahon, G Whitlock; Busselton: MW Knuiman; Canberra-Queanbeyan: H Christensen; Capital Iron and Steel Company Hospital Cohort (CISCH): J Zhou, XH Yu; Capital Iron and Steel Company: XG Wu; Civil Service Workers: A Tamakoshi; CVDFACTS: WH Pan; Electricity Generating Authority of Thailand (EGAT): P Sritara; East Beijing: ZL Wu, LQ Chen, GL Shan; Fangshan Farmers: DF Gu, XF Duan; Fletcher Challenge: S MacMahon, R Norton, G Whitlock, R Jackson; Guangzhou: YH Li; Guangzhou Occupational: TH Lam, CQ Jiang; Hisayama: M Fujishima, Y Kiyohara, H Iwamoto; Hong Kong: J Woo, SC Ho; Huashan: Z Hong, MS Huang, B Zhou; Kinmen: JL Fuh; Kounan Town: H Ueshima, Y Kita, SR Choudhury; Korean Medical Insurance Company: I Suh, SH Jee, IS Kim; Melbourne Cohort: G Giles; Miyama: T Hashimoto, K Sakata; Newcastle: A Dobson; Ohasama: Y Imai, T Ohkubo, A Hozawa; Perth: K Jamrozik, M Hobbs, R Broadhurst; Saitama: K Nakachi; Seven Cities: XH Fang, SC Li, QD Yang; Shanghai Factory Workers: ZM Chen; Shibata: H Tanaka; Shigaraki: Y Kita, A Nozaki, H Ueshima; Shirakawa: H Horibe, Y Matsutani, M Kagaya; Singapore Heart: K Hughes, J Lee; Singapore 92: D Heng, SK Chew; Six Cohorts: BF Zhou, HY Zhang; Tanno/Soubetsu: K Shimamoto, S Saitoh; Tianjin: ZZ Li, HY Zhang; Western Australian AAA Screenees: P Norman, K Jamrozik. Xi'an: Y He, TH Lam; Yunnan: SX Yao. (The studies in italics contributed data to these analyses.)
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Acknowledgments |
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This project has received grants from the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand, the US National Institutes of Health, and an unrestricted educational grant from Pfizer Inc. R Huxley is supported by a University of Sydney SESQUI Postdoctoral Fellowship and C Lawes is supported by a National Heart Foundation (New Zealand) Fellowship.
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* Members listed in acknowledgements.
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1 World Health Organisation. Towards Age-Friendly Primary Health Care. Geneva: WHO, 2004.
2 Castelli WP. Epidemiology of coronary heart disease: the Framingham Study. Am J Med 1984;76:4–12.[CrossRef][Web of Science][Medline]
3 World Health Organisation. MONICA Project. Myocardial infarction and coronary deaths in the World Health Organisation MONICA Project: registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 1994;90:583–612.
4 Jousilahti P, Vartianen E, Tuomilehto J, Pushka P. Sex, age, cardiovascular risk factors, and coronary heart disease: A prospective follow-up study of 14,786 middle-aged men and women in Finland. Circulation 1999;99:1165–72.
5 WHO. The Atlas of Heart Disease and Stroke. Geneva: WHO, 2004.
6 Asia Pacific Cohort Studies Collaboration. Determinants of cardiovascular disease in the Asia Pacific region: protocol for a collaborative overview of cohort studies. CVD Prevention 1999;2:281–89.
7 Asia Pacific Cohort Studies Collaboration. Blood pressure and cardiovascular disease in the Asia Pacific Region. J Hypertens 2003;21:707–16.[CrossRef][Web of Science][Medline]
8 Asia Pacific Cohort Studies Collaboration. Cholesterol, coronary heart disease and stroke in the Asia Pacific region. Int J Epidemiol 2003;32:563–72.
9 Asia Pacific Cohort Studies Collaboration. Body mass index and cardiovascular disease in the Asia Pacific Region: an overview of 33 cohorts involving 310,000 participants. Int J Epidemiol 2004;31:1–8.
10 Asia Pacific Cohort Studies Collaboration. The effects of diabetes on the risks of major cardiovascular diseases and death in the Asia-Pacific Region. Diabetes Care 2003;26:360–66.
11 Woodward M. Epidemiology: Study Design and Data Analysis. 2nd edn. Boca Raton: Chapman and Hall/CRC, 2005.
12 Burt VL, Cutler JA, Higgins M et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population. Data from the health examination surveys, 1960 to 1991. Hypertension 1995;26:60–69.
13 Harris MI, Flegal KM, Cowie CC et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 1998;21:518–24.[Abstract]
14 Anderson KM, Wilson PW, Garrison RJ, Castelli WP. Longitudinal and secular trends in lipoprotein cholesterol measurements in a general population sample. The Framingham Offspring Study. Atherosclerosis 1987;68:59–66.[CrossRef][Web of Science][Medline]
15 Criqui MH, Frankville DD, Barrett-Connor E, Klauber MR, Holdbrook MJ, Turner JD. Change and correlates of change in high and low density lipoprotein cholesterol after six years: a prospective study. Am J Epidemiol 1983;118:52–59.
16 Newschaffer CJ, Bush TL, Hale WE. Aging and total cholesterol levels: cohort, period, and survivorship effects. Am J Epidemiol 1992;136:23–34.
17 Weijenberg MP, Feskens EJ, Kromhout D. Age-related changes in total and high-density-lipoprotein cholesterol in elderly Dutch men. Am J Public Health 1996;86:798–803.
18 Johnson A. Sex differentials in coronary heart disease: the explanatory role of primary risk factors. J Health Soc Behav 1977;18:46–54.[CrossRef]
19 Matthews KA, Meilahn E, Kuller LH, Kelsey SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N Engl J Med 1989;321:641–46.[Abstract]
20 Newschaffer CJ, Bush TL, Hale W. Aging and total cholesterol levels: cohort, period and survivorship effects. Am J Epidemiol 1992;136:23–34.
21 Garry PJ, Hunt WC, Koehler KM, VanderJagt DJ, Vellas BJ. Longitudinal study of dietary intakes and plasma lipids in healthy elderly men and women. Am J Clin Nutr 1992;55:682–88.
22 Asia Pacific Cohort Studies Collaboration. Does sex matter in the associations between classical risk factors and fatal coronary heart disease? J Women's Health 2005;14:820–8.[CrossRef]
23 Popkin BM, Horton S, Kim S, Mahal A, Shuigao J. Trends in diet, nutritional status, and diet-related noncommunicable diseases in China and India: the economic costs of the nutrition transition. Nutr Rev 2001;59:379–90.[Web of Science][Medline]
24 He Y, Lam TH. A review on studies of smoking and coronary heart disease in China and Hong Kong. Chin Med J 1999;112:3–8.[Medline]
25 Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903–13.[CrossRef][Web of Science][Medline]
26 Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003;326:1419–23.
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