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Logo of japanaththrJournal of Atherosclerosis and Thrombosis
J Atheroscler Thromb. 2017 March 1; 24(3): 258–261.
PMCID: PMC5383542

Risk Factor of Cardiovascular Disease Among Older Individuals

See article vol. 24: 290–300

In spite of the increase in the attribute of metabolic disorders to the incidence of cardiovascular disease (CVD), hypertension remains the most important risk factor in Japanese people1, 2). Hypertension accounted for more than one-third of stroke incidence in the mostly middle-aged participants of the Japan Public Health Center-based prospective (JPHC) Study3). It is an established risk factor of stroke in much older individuals too4, 5). In the Suita Study, the cumulative lifetime risk of stroke at the age of 75 years was 11.8% and 13.1% for hypertensive men and women, respectively; the risk lowers to 5.5% and 5.3% for men and women without hypertension, respectively6). Furthermore, it was reported in this issue of the Journal of Atherosclerosis and Thrombosis that hypertension was the only risk factor significantly associated with stroke incidence in individuals aged ≥ 75 years (old-old) and 60–74 years (young-old) in the Ohasama Study7). These results from the observational studies816) together with findings of previous intervention studies1720) confirm the appropriateness of the current hypertension guidelines for the management of hypertension for older individuals in Japan21) (Table 1).

Table 1.
Recent (published in 2013 or later) epidemiological findings of blood pressure's association with cardiovascular disease in the older individuals

Evidence from observational studies generally requires careful interpretation. It is judicious to use some kind of checklist when making a causal judgment22). For example, diabetes was positively associated with stroke incidence in the young-old participants, but the association was not found in the old-old participants in the Ohasama Study. The authors raised a possibility of selection (bias) for this unexpected finding, i.e., those who survived to be old-old might have a resistance to the effect of diabetes on the cardiovascular system. Apart from this authors' idea, we can discuss the issue again using the checklist (Table 2).

Table 2.
Checklist for interpreting epidemiological studies

Confounding refers to a situation where the association between two variables (causal- and outcome-assumed variables) arises (becomes stronger) or diminishes (becomes weaker) under the existence of a confounding variable that is associated with both the variables. We cannot expect that all the confounding variables are always measured. A confounding variable is not a mediator; but is a factor that is generated by the causal variable and pathophysiologically affects the outcome variable by definition. In the study, nutritional condition and body habitus might have been the confounding variables if they had been related to both diabetes and stroke incidence23, 24). Another possible confounding factor is health service usage. If blood pressure of those with diabetes had been managed more carefully than those without or if they had received more preventive measures, such as aspirin, this could have confounded the association.

We present a possible scenario of reverse causation here. The subjects who were likely to develop stroke in future could have been less likely to have, be aware of, or report diabetes at baseline. With that being said, this scenario would have hardly happened.

Measurement sometimes causes misclassification. It occurs in both causal and outcome variables. In the study, diabetes was self-reported. In general, the validity of self-report at baseline is not influenced by the outcome in prospective studies. Thus, this kind of misclassification is usually called non-differential misclassification and is likely to lead to attenuation of the association toward null. An example of differential misclassification related to self-report is recall bias. Differential misclassification of the outcome variable occurs if surveillance or case definition is influenced by baseline variables. In such instances, the association between the causal and outcome variables appears stronger or weaker than in reality. In the study, the association between diabetes and stroke incidence was null (not inverse) in the old-old individuals. Inaccurate self-report on diabetes status may partly explain that finding. The authors mentioned the possibility as a study limitation that the validity of self-report on diabetes decreased as the age of the subjects increased.

Finally, can we generalize the present findings? Characterization of the studied participants was simple but comprehensive in the article. The baseline survey was conducted in 1998. The study excluded those with a history of stroke while included those with histories of heart and kidney diseases. Confounding variables, such as height and weight, and medical histories were obtained via self-reporting. This information raises the possibilities of residual confounding of health statuses at baseline and unmeasured confounding of other lifestyle factors, such as diet. However, the participation rate was satisfactory. Approximately 90% of the population agreed to participate in the study, and 80% of the population was actually analyzed. Therefore, the present findings would be generalizable to another geriatric population, like Ohasama, in spite of the possibility of residual and unmeasured confounding.

Conflict of Interest



1) Sugiyama D, Okamura T, Watanabe M, Higashiyama A, Okuda N, Nakamura Y, Hozawa A, Kita Y, Kadota A, Murakami Y, Miyamatsu N, Ohkubo T, Hayakawa T, Miyamoto Y, Miura K, Okayama A, Ueshima H, Group NDR : Risk of hypercholesterolemia for cardiovascular disease and the population attributable fraction in a 24-year Japanese cohort study. J Atheroscler Thromb, 2015; 22: 95-107 [PubMed]
2) Teramoto T, Sasaki J, Ishibashi S, Birou S, Daida H, Dohi S, Egusa G, Hiro T, Hirobe K, Iida M, Kihara S, Kinoshita M, Maruyama C, Ohta T, Okamura T, Yamashita S, Yokode M, Yokote K.: Diabetes mellitus. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan--2012 version. J Atheroscler Thromb, 2014; 21: 93-98 [PubMed]
3) Yatsuya H, Iso H, Yamagishi K, Kokubo Y, Saito I, Suzuki K, Sawada N, Inoue M, Tsugane S.: Development of a point-based prediction model for the incidence of total stroke: Japan public health center study. Stroke, 2013; 44: 1295-1302 [PubMed]
4) Fujiyoshi A, Ohkubo T, Miura K, Murakami Y, Nagasawa SY, Okamura T, Ueshima H, Observational Cohorts in Japan Research G : Blood pressure categories and longterm risk of cardiovascular disease according to age group in Japanese men and women. Hypertens Res, 2012; 35: 947-953 [PubMed]
5) Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies C : 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: 1903-1913 [PubMed]
6) Turin TC, Okamura T, Afzal AR, Rumana N, Watanabe M, Higashiyama A, Nakao Y, Nakai M, Takegami M, Nishimura K, Kokubo Y, Okayama A, Miyamoto Y.: Hypertension and lifetime risk of stroke. J Hypertens, 2016; 34: 116-122 [PubMed]
7) Murakami K, Asayama K, Satoh M, Inoue R, Tsubota-Utsugi M, Hosaka M, Matsuda A, Nomura K, Murakami T, Kikuya M, Metoki H, Imai Y, Ohkubo T.: Risk Factors for Stroke among Young-Old and Old-Old Community-Dwelling Adults in Japan: the Ohasama Study. J Atheroscler Thromb, 2017; 24: 290-300 [PMC free article] [PubMed]
8) Koh AS, Talaei M, Pan A, Wang R, Yuan JM, Koh WP.: Systolic blood pressure and cardiovascular mortality in middle-aged and elderly adults - The Singapore Chinese Health Study. Int J Cardiol, 2016; 219: 404-409 [PMC free article] [PubMed]
9) Dong C, Della-Morte D, Rundek T, Wright CB, Elkind MS, Sacco RL.: Evidence to Maintain the Systolic Blood Pressure Treatment Threshold at 140 mm Hg for Stroke Prevention: The Northern Manhattan Study. Hypertension, 2016; 67: 520-526 [PMC free article] [PubMed]
10) Rosero-Bixby L, Coto-Yglesias F, Dow WH.: Pulse blood pressure and cardiovascular mortality in a population-based cohort of elderly Costa Ricans. J Hum Hypertens, 2016; 30: 555-562 [PMC free article] [PubMed]
11) Wu CY, Hu HY, Chou YJ, Huang N, Chou YC, Li CP.: High Blood Pressure and All-Cause and Cardiovascular Disease Mortalities in Community-Dwelling Older Adults. Medicine (Baltimore), 2015; 94: e2160. [PMC free article] [PubMed]
12) Zheng L, Li J, Sun Z, Zhang X, Hu D, Sun Y.: Relationship of Blood Pressure With Mortality and Cardiovascular Events Among Hypertensive Patients aged > / = 60 years in Rural Areas of China: A Strobe-Compliant Study. Medicine (Baltimore), 2015; 94: e1551. [PMC free article] [PubMed]
13) Yi SW, Hong S, Ohrr H.: Low systolic blood pressure and mortality from all-cause and vascular diseases among the rural elderly in Korea; Kangwha cohort study. Medicine (Baltimore), 2015; 94: e245. [PMC free article] [PubMed]
14) Banach M, Bromfield S, Howard G, Howard VJ, Zanchetti A, Aronow WS, Ahmed A, Safford MM, Muntner P.: Association of systolic blood pressure levels with cardiovascular events and all-cause mortality among older adults taking antihypertensive medication. Int J Cardiol, 2014; 176: 219-226 [PMC free article] [PubMed]
15) Mohebi R, Mohebi A, Ghanbarian A, Momenan A, Azizi F, Hadaegh F.: Is systolic blood pressure below 150 mm Hg an appropriate goal for primary prevention of cardiovascular events among elderly population? J Am Soc Hypertens, 2014; 8: 491-497 [PubMed]
16) Zhao W, Katzmarzyk PT, Horswell R, Wang Y, Li W, Johnson J, Heymsfield SB, Cefalu WT, Ryan DH, Hu G.: Aggressive blood pressure control increases coronary heart disease risk among diabetic patients. Diabetes Care, 2013; 36: 3287-3296 [PMC free article] [PubMed]
17) Wei Y, Jin Z, Shen G, Zhao X, Yang W, Zhong Y, Wang J.: Effects of intensive antihypertensive treatment on Chinese hypertensive patients older than 70 years. J Clin Hypertens (Greenwich), 2013; 15: 420-427 [PubMed]
18) Zhang Y, Zhang X, Liu L, Zanchetti A, Group FS : Is a systolic blood pressure target < 140 mmHg indicated in all hypertensives? Subgroup analyses of findings from the randomized FEVER trial. Eur Heart J, 2011; 32: 1500-1508 [PubMed]
19) Bangalore S, Gong Y, Cooper-DeHoff RM, Pepine CJ, Messerli FH.: 2014 Eighth Joint National Committee panel recommendation for blood pressure targets revisited: results from the INVEST study. J Am Coll Cardiol, 2014; 64: 784-793 [PMC free article] [PubMed]
20) Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, Chertow GM, Fine LJ, Haley WE, Hawfield AT, Ix JH, Kitzman DW, Kostis JB, Krousel-Wood MA, Launer LJ, Oparil S, Rodriguez CJ, Roumie CL, Shorr RI, Sink KM, Wadley VG, Whelton PK, Whittle J, Woolard NF, Wright JT, Jr., Pajewski NM, Group SR : Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged > / = 75 Years: A Randomized Clinical Trial. JAMA, 2016; 315: 2673-2682 [PMC free article] [PubMed]
21) Chapter 8. Hypertension in the elderly. Hypertens Res, 2014; 37: 325-332
22) Hu F.: Interpreting epidemiologic evidence and causal inference in obesity research. In: Obesity Epidemiology, pp38-52, Oxford University Press, New York, 2008
23) Noda H, Iso H, Irie F, Sairenchi T, Ohtaka E, Doi M, Izumi Y, Ohta H.: Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study. Circulation, 2009; 119: 2136-2145 [PubMed]
24) Kroll ME, Green J, Beral V, Sudlow CL, Brown A, Kirichek O, Price A, Yang TO, Reeves GK, Million Women Study C : Adiposity and ischemic and hemorrhagic stroke: Prospective study in women and meta-analysis. Neurology, 2016; [PMC free article] [PubMed]

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