Response to Selection Bias, Confounding, or Information Bias?
Kabir’s1 comments highlight the differences between epidemiology in theory and in practice. The recruitment procedures were stated clearly. The subjects consisted of consecutive new referrals suspected to have elevated blood pressure to a hypertension unit that provides confirmatory ambulatory blood pressure monitoring. Not on treatment at the time of clinical and hemodynamic assessment is not the same as “left untreated,” because it is important to establish the diagnosis of hypertension before lifelong treatment. However desirable in epidemiological terms, it would be unethical to leave patients untreated. Kabir1 argues that we have used a selected cohort of patients with hypertension, which is not representative of the general population. From the title of our article, it is obvious that we never presented the cohort as “general population.” Nonetheless, subjects with high blood pressure do represent a large section of the community; indeed, in a population >50 years of age, only a minority have normal blood pressure.2
Kabir1 argues about time-varying exposures, which are difficult to quantify. In this particular study, we had to reflect up to 50 years of exposure to cigarettes as an analyzable variable. The duration of smoking cessation has been used in large epidemiological studies.3 It is very difficult to quantify a lifetime of exposures, such as physical activity or dietary habits, into a single unit. How, for example, do we address the situation where some of our subjects were international athletes for 8 to 10 years but then became obese and sedentary for the subsequent 12 years? In part, we addressed this issue in our earlier study where, in young subjects, physical activity appears partially to protect from the adverse effects of cigarette smoking on arterial stiffness.4 We do not “argue” that smoking even 1 cigarette immediately raises arterial stiffness4 and were referencing the well-established fact in part to emphasize that any exposure to cigarette smoking may be hazardous.
Addressing the criticism regarding not forcing lipid parameters or waist:hip ratio in the model, we would have had to use “force” to include these factors in a multiple regression model, because none were related to arterial stiffness in this study. However, subsequent analysis including such variables shows that pulse wave velocity remains significantly associated with smoking status in a linear fashion after adjustment for age, sex, mean arterial pressure, and heart rate even after adding other factors such as waist:hip ratio (P=0.029), triglycerides (P=0.007), and total cholesterol (P=0.01) in a multiple regression model.
In his criticism of pulse wave velocity, which is the “gold standard” measure of arterial stiffness,5 Kabir quotes not an article but a piece of correspondence,6 which in fact does not actually criticize pulse wave velocity! Similarly, his criticism of lack of transparency may reflect a failure to carefully read our article.
Kabir’s1 main criticism of our study, mentioned repetitively, that we performed a nonrandomized observational study, perhaps underlines the difference between the theoretical epidemiologist and those who work with available data. It will never be ethically justified to randomly assign individuals to smoking, nonsmoking, or ex-smoking!
Kabir Z. Selection bias, confounding, or info bias? Hypertension. 2007; 50: e9.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Rocella EJ and the National High Blood Pressure Education Program Co-ordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003; 42: 1206–1252.
Mahmud A, Feely J. Effect of smoking on arterial stiffness and pulse pressure amplification. Hypertension. 2003; 41: 183–187.
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I. B, Struijker-Boudier H. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006; 27: 2588–2605.
Franks PW. Comparing the roles of physical activity and fitness in arterial stiffness: how important is exposure measurement error? Hypertension. 2005; 45: e1.