Report an error   

Submitted: 12 September 2011 Modified: 16 May 2019
HERDIN Record #: PCHRD09121111091638

Frailty modeling of cardiovascular risk factors among Filipino.

Bridith S. Penaranda

See More

BACKGROUND: At present, majority of Filipino physicians are aware only of the Framingham list of CVD risk factors, and usually is the basis in identifying the Filipino patient's risk for heart disease accordingly. Some variances in the Filipino lifestyle and genetic profile may require some modifications on the existing risk equation.

OBJECTIVE: This aims to create a prediction model which can estimate CVD risk among Filipinos based on currently known risk factors using survival analysis.
Main objective: To derive a multivariate survival model for cardiovascular mortality among Filipino adults.
Specific objectives:
1. To derive a WEibull parametric model for cardiovascular mortality using age, gender, low density lipoprotein (LDL), high -density lipoprotein (HDL). blood pressure, diabetes and smoking as risk factors.
2. To determine if incorpoaration of a frailty component to the parametric regression model is necessary to account for the other unmeasured risk factors
3. If a frailty component is necessary, then compare the two frailty models namely, Gamma and Inverse Gaussian distribution.

METHODS: Six out of 13 national regions were included in the cohort. There were 1749 individuals included. Survival techniques specifically Weibull regression model and frailty model were fitted to the data.

RESULTS: The study found five risk factors -age, gender, blood pressure, DM, and smoking-significant in predicting death due to cardiovascular disease. The effect of HDL and LDL was not found statistically significant in the model development.

CONCLUSIONS: Younger female individuals with non-elevated blood pressure, non-diabetics and who do not smoke have a greater chance of survival. A sex-specific model using Weibull distribution was chosen to be the distribution of choice. Incorporating fraity was not needed in the data.

Publication Type
Thesis Degree
Public Health
Publication Date
April 2011
LocationLocation CodeAvailable FormatAvailability
Philippine Council for Health Research and Development Library RC669 P46 2011 Abstract Print Format (Request Document)
1. (2003, November 30). World Health Organization Fact Sheets. Top Ten Leading Causes of Death (Online). . Retrieved from:
2. (2009, November 30). DOH. Department of Health -Philippines (Online) Cited: February 9, 2010. . Retrieved from:
3. "The Task Force on Diabetes and Cardiovascular Disease of he European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes. Guidelines on Diabetes, Pre-diabetes, and Cardiovascular Disease: Executive Summary" European Heart Journal 28, 88-136, 2007
4. Liu, J . "Predictive value for the Chinese Population of the Framingham CHD Risk Assessment Tool Compared with the Chinese Multi-provincial Cohort Study" JAMA 291(21): 2591-2595, 2004
5. Despres, J P, Lemieux, I , et al, . "HDL Cholesterol as a Marker of oronary Heart Disease Risk: The Quebec Cardiovascular Study" Atherosclerosis 153(2): 263-272, December 2000
6. Feresu, S , et al, . "The Frequency and Distribution of Cardiovascular Disease Risk Factors among Nebraska Women Enrolled in the WISEWOMAN Screening Program" J Women 17(4): 607-617, 2008
7. Kannel, W , McGee, D , Gordon, T . "A General Cardiovascular Risk Profile: The Framingham Study" Am J Cardio 38, 46-51, 1976
8. Lee, J , Ma, S , et al, . "Hypertension, Concurrent Cardiovascular Risk Factors and Mortality: the Singapore Cardiovascular Cohort Study" Journal of Human Hypertension 2, 468-474, 2008
9. Menotti, A , Keys, A , et al, . "Twenty-Five-Year Mortality From Coronary Heart Disease and its Prediction in Five Cohorts of Middle-Aged Men in Finland, the Netherlands, and Italy" Prev Med 19, 270-278, 1990
10. Pencina, M J, D, R , et al, . "Predicting the 30-year Risk Cardiovascular Disease: The Framingham Heart Stusy " Circulation 19(24): 3078-3084, 2009
11. Chobanian, A V. "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" JAMA 289(19): 2560-2572, 2003
12. D, R , Vasan, R , et al, . "General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Study" Circulation 117, 743-753, 2008
13. Brindle, P , Jonathan, E , et al, . "Predictive Accuracy of the Framingham Coronary Risk Score in British Men, Prospective Cohort Study" BMJ 327, 1267-1270, November 2003
14. Branwald, E , et al, . Braunwald. A Textbook of Cardiovascular Disease 7th Ed. Philadephia: Elsevier Saunders, 2005.
15. Mackay, J , Mensah, J . "Atlas of Heart Disease and Stroke" WHO S1, 2004
16. Chambless, L , Dobson, A J, et al, . "On the Use of Logistic Risk Score in Predicting Risk of Coronary Heart Disease" Stat Med 9, 385-396, 1990
17. Prasad, D S, Kabir, Z , et al, . "Smoking and CadiovascularHealth: A review of the Epidemiology, Pathogenesis, Prevention and control of tobacco" Indian J Med Sci 63(11): 520-533, 2009
18. Willet, W C, Green, A , et al, . "Relative and absolute Excess Risk of Coronary Heart Disease among Wmen who Smoke Cigarettes" N England JMed 317, 1303-1309, 1987
19. Yusuf , S , Hawken, S , et al, . "Effect of Potentially Modifiable Risk Factors Associated with Myocardial Infarction in 52 Countries (INTERHEART STUDY). Case-control study" Lancet 943(38): 937-952, 2004
20. Wannamethee, S G, Shaper, A G, Perry, J . "Smoking as aModifiable Risk Factor for Type 2 Diabetes in Middle-aged Men" Diabetes Care 24(9): 1590-1595, 2001
21. Heyden, S , Heiss, G , et al, . "The Combined Effect of Smoking and Coffee Drinking on LDL and HDL Cholesterol" Circulation 60, 22-25, 1979
22. Dochi, M , Sakata, K , Oishi, M . "Smoking as an Independent Risk Factor for Hypertension: A 14-Year Longitudinal Study in Male Japanese Workers " The Tohoku Journal of Experimental Medicine 217(1): 37-43, 2009
23. Iwashita, M , Matsushita, Y , et al, . "Relation of serum total Cholesterol and other factors of risk of cerebral infarction in Japanese men with hypercholesterolemia" Circ J 69, 1-6, 2005
24. Gordon, D J, Probstfield, J , et al, . "High-density Lipoproteiin Cholesterol and Cardiovascular Disease: Four Prospective American studies." Circulation 79, 8-15, 1989
25. Corti, M C, Guralnik, J , et al, . "HDL Cholesterol Predicts Coronary Heart Disease Mortality in Older Persons" JAMA 274, 539-544, 1995
26. Chhatriwalla, A , Nicholls, S , et al, . "Low Levels of Low-Density Lipoprotein Cholestrerol and Blood Pressure and Progression of Coronary Atherosclerosis" J Am Coll Cardiol 53, 1110-1115, 2009
27. Jousilahti, P , Vartiainen, E , et al, . "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 99, 1165-1172, 1999
28. Williams, B . Hypertension in Diabetes. London: Martin Dunitz, 2003.
29. Lee, W L, Cheung, A M, et al, . "Impact of Diabetes on Coronary Artery Disease in Women and Men: Meta-analysis of Prospective Study" Diabetes Care 23, 962-968, 2000
30. Grundy, S , Pasternak, R , et al, . "Assessment of Cardiovascular risk by Use of Multiple-risk-factor Assessment Equation: A Statement for Healthcare Professionals from the American Heart Association and American College of Cardiology" Circulation 100, 1481-1492, 1999
31. Mancia, G . "The Association of Hypertension and Diabetes: Prevalence , Cardiovascular Risk and Protection by Blood Pressure Reduction" Acta Diabetol 42, S17-S25, 2005
32. Nesto, R . "LDL Cholesterol Lowering in Type 2 Diabetes : What is the Optimum Approach? " Clinical Diabetes 26(1): 8-13, 2008
33. Booth, G L, Kapral, M , et al, . "Relation between Age and cardiovascular Disease in Men and Women with Diabetes compare with Non-diabetic people: A Population-basedRetrospective Cohort Study" Lancet , 29-36, 2006
34. Lawes, C M, Hoorn, V , et al, . "Blood Pressure and the Global Burden of Disease 2000. Part II: Estimate of Attributable Burden" JbHypertens 24, 423-430, 2006
35. Nilsson, G , Ohrvik, J , et al, . "Ten-Year Survival in 75-Year-Old Men and Women: Predictive Ability of Total Cholesterol, HDL-C, and LDL-C" Current Gerontology and Geriatrics Research 7, 1-8, 2009
36. Terry, D , Pencina, M J, et al, . "Cardiovascular Risk Factors Predictive for Survival and Morbidity-Free Survival in the Oldest-Old Framingham Heart Study Participants" J Am Geriatric Soc 53, 1944-1950, 2005
37. Collett, D . Modelling Survival Data in Medical Research. Chapman and Hall, 1994. S1.
38. Kleinbaum, David , Klein, Mitchel . Survival Analysis: Self Learning Text 2nd Ed. New York: Springer, 2005.
39. Vittinghof, E , Glidden, D , Shiboski, S , McCullogh, C . Regression Methodsin Biostatistics. New York: Springer, 2005.
40. Duchateau, L , Janssen, P . The Frailty Model. New York: Springer, 2008.
41. Cleves, M . An Introduction to Survival Analysis . Texas: Stata Press, 2008.
42. Lemenshow , S , Hosmer, D . Applied Survival Analysis. New York: John Wiley & Sons, 1999.
43. Karim, M . Frailty Models. Bangladesh. 2008. (MS) University of Dhaka,
44. Klein, J , Moeschberger, M . Survival Analysis Techniques for Censored andTruncated Data. New York: Springer-Verlag 2nd edition, 2003.
45. Houggaard, P , Myglegaard, P , Borch-Johnsen, K . "Heterogeneity models of Susceptibility, with Application to Diabetic Neuropathy" Biometrics 50, 1178-1188, 1994
46. Gyimah, S . Childhood Mortality and Reproductive Behavior in Ghana and Kenya: An Examination of Frailty and Nonfrailty Models. London. 2001. (PhD) University of Western Ontario,
47. Zdravkovic, S , Wienke, A , et al, . "Heritability of Death from Coronary Heart Disease: a 36-year Followw up of20,966 Swedish twins" Journal of Internal Medicine 252, 247-254, 2002
48. Reyes, C . Heterogeneity in Long-Term Survivors: A Frailty wiyh Immunes. Manila. 2006. (MS) University of the Philippines Diliman,
49. Cui, J , Forbes, A , et al, . "Parametric Conditional Frailty Models for Recurrent Cardiovascular Events in the Lipid study" Clinical Trials 5, 565-574, 2008
50. Rothman, K , Greenland, S , Lash, T . Modern Epidemiology, 3rd Ed. Lipponcott, Williams & Wilkins, 2008. S1.
51. World Health Organization, Definition, Diagnosis and Classification of Diabeetes Mellitus and its Complications Report of a WHO Consultation. Part I: Diagnosis and Classification of Diabetes Mellitus, WHO Department of Noncommunicable Disease Surveillance Geneva: 1999. 1-59.
52. Kleinbaum, D , Sullivan, K , Barker, N . A Pocket Guide to Epidemiology . New York: Springer, 2007.
53. Perera, W . Risk Factors of Cardiovascular Disease in a Cohort of Estonian Postmenopausal Women. 2005. (MS) University of Hasselt,
54. Jenkins, S . Summer course work on Survival Analysis. Institute for Social and Economic Research. University of Essex, Wivenhoe Park, Colchester, United Kingdom: 2002.
55. Wilson, P , D, R , Ralph, B , Levy, Daniel . "Prediction of Coronary Heart Disease Using Risk Factor Categories" Circulation 97, 1837-1847, 1998
56. Soria, M L, Sy, R , et al, . "The incidence of type 2 diabetes mellitus in the Philippines: a 9-year cohort study" Diabetes Research and Clinical Practice 86, 130-133, 2009
57. D, R B, Grundy, S , et al, . "Validation of the Framingham Coronary Heart Disease Prediction Scores" JAMA 285(2): 181-187, 2001
58. Daber, T , Meadors, G , Moore, F . "Epidemiological Approaches to Heart Disease: The Framingham Study" Am J Public Health 41, 279-286, 1951
59. Experian Simmons Research. marketing to Women. Addressing Women and Women.
60. Cromie, W . Why Women Live Longer?. Gazette University of Harvard: 1998.
61. Amuron, B , et al, . "Mortality and loss-to-follow-up durngbthe Pre-treatment Perid in an Antiretroviral Therapy programme under Normal Health Service Conditions in Uganda" BMC public health 9, 920, 2009
62. Rodriguez, M , Llorca, J . "Bias" J Epidemiol Community Health 58, 635-641, 2004
63. Goodlice, j . The Hazards of Time-Varying Covariate.. Bringham Young University: Lecture Notes . December 2003,
64. (). Cardiovascular Disease Prevalence and Mortality. U.S. Environmental Protection Agency (Online) December 3, 2009 (Cited February 10, 2010. . Retrieved from:
65. Jacob, Jr, D R, Mebane, I L, et al, . "High Density Lipoprotein Cholesterol as a Predictor of Cardiovascular Disease mortality in Men and Women: The Follow-up study of the Lipid Research Clinics Prevalence Study" Am J Epidemiol 131(1): 32-47, January 1990
66. Hyvarinen, M , Tuomilehto, J , et al, . "The Impact of Diabetes on Coronary Heart Disease Differs from that on Ischaemic Stroke with regard to the Gender " Cardiovascular Diabetology 8(17): 2009
67. Epstein, M , Sowers, J . "Diabetes Mellitus and Hypertension" Hypertension 19, 403-418, 1992
68. Manton, K , Stallard, E , Vaupel, J . "Alternative Models for the Heterogeneity of Mortality Risks Among the Aged" J Am Statistical Association 81(395): 635-644, 1986
69. Hougaard, P . "Life table Methods for Heterogeneous Populations: Distributions describing the Heterogeneity" Biometrika 71(4): 75, 1984
70. Heish, P . "On Heteroscedastic Hazards Regression Models: Theory and Application" Journal of the Royal Statistical Society Series B. Methodological 63(1): 63-71, 2001
71. Liang, K , Self, S , et, al . "Some Recent Developments for Regression Analysis of Multivariate Failure Time Data" Lifetime Data Analysis , 403-415, 1995
72. Hosmer, D , Lemeshow, S . Applied Survival Analysis. Canada: Wiley & Sons Inc, 1999.
73. Batty, G B, Lee, I M. "Physical Activity and Coronary Heart Diseae" BMJ 328(8): 1089-1090, 2004
74. Rimm, E B, Meir, J , et al, . "Body Size and Fat Distribution as Predictors of Coronary Heart Disease among Middle-Aged and Older US Men" Am J Epidemiology 141(12): 1117-1127, 1995
75. "Seventh Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure" US Department of Health and human Services, 2004. 12.
76. McGilchrist, C A, Aisbett, C W. "Regression with Frailty in Survival Analysis" Biometrics 47, 461-466, 1991
77. Aalen, O , Tretli, S . "Analysing Incidence of Testis Cancer by Means of a Frailty Model" Cancer Causes and Control 10(4): 285-292, 1999
78. Inobaya, A . Comparing the Goodness-of-Fit and Estimates of the Cox Proportional Hazards and the Exponential and Weibull Parametric Models in the Multivariate Survival Analysis of the Philippine Lung Center Data. Manila. 2008. College of Public Health,
79. Dupont, W . Statistical Modeling for Biomedical Researchers. New York: Cambridge University Press, 2002.
80. Whincup, P , Gilg, J , et al, . "Passive Smoking and Risk of Coronary Heart Disease and Stroke: Prospective Study with Cotinine measurement " BMJ 329, 200-205, 2004
81. Smith , T , Smith, B . "Survival Analysis and the Application of Cox Proportional Modeling Using SAS" Statistic, Data Analysis and Data Mining , 224-226, 2000
82. Stefanon, N , Tsismenakis, A J, et al, . "Blood Pressure in Firefighters, PoliceOfficers, and Other Emergency Responders" Am J Hypertens 22, 11-20, 2009
83. (). US Department of Health and Human Services. The Health Benefitsof Smoking Cessation: A Report of the Surgeon General, DHHS Publication No. (CDC) 90-8416. Rockville, MD: US Department of Health and Human Services, Public health service (Online). . Retrieved from: http://www.cdc-gov/tobacco/data-statistics/sgr/2004/index.html
84. (2003, November 30). World Health Organization. Cardiovascular disease: Prevention and Control. (Online). . Retrieved from:
85. Parish, S , Collins, R , et al, . "Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14000 cases and 32000 controls in the United Kingdom" BMJ 311, 471-477, August 1995
86. Vaupel, J , Yashin, A . "Heterogeneity" The American Statistician 39, 176-185, 1985
87. Chamberlain, G . "Longitudinal Analysis of Labor Market Mata, Chapter Heterogeneity" , 1985
88. Clayton , D . "A Model for Association in Bivariate Life tables and its Application in Epidemiological Studies of Familial Tendency" Biometrika 65(1): 141, 1978
89. Clayton , D , Cuzick, J . "The EM Algorithm for Cox" Applied Statisticss 34(2): 148, 1985
90. Vaupel, J , Manton, K , Stallard, E . "Heterogeneity in Individual Frailty on the Dynamics of Mortality" Demography 16(3): 439-454, 1979
91. Yashin, A , Lachine, L . "Genetic Analysis of Durations: Correlated Frailty Model Applied to Survival of danish Twins" Genet Epidemiol 2(5): 529-538, 1995
92. Yashin, A , Lachine, A . "How Frailty Models can be used for Evaluating Longevity Limits: Taking Advantage of an Interdisciplinary Approach" Demography 34(1): 31-48, 1997
93. Hougaard, P . "Survival models for heterogenous populations derived from stable distributions" Biometrika 73(2): 387-396, 1986
94. Jisheng, C , et al, . "Parametric conditional frailty models for recurrent cardiovascular events in the lipid study " Clinical Trials 5, 565-574, 2008
95. Menotti, A , Lanti, M , Puddu, P E. "Twenty-five-year Cardiovascular Disease Disease Incidence among Middle -aged men, Disease Burden, Time shape, Predictors, Risk probabilities" Ital Heart J 1(11): 749-757, 2000
96. "World Health Organization, Defination, Diagnosis and Classification of Diabetes Mellitus and its Complication." Report of a WHO Consultation Part I: Diagnosis and Classification of Diabetes Mellitus, WHO Department of Nncommunicable Disease Surveillance, Geneva , 1-59, 1999. Retrieved from: http://http//