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RESEARCH: Robert Clarke, Jonathan Emberson, Astrid Fletcher, Elizabeth Breeze, Michael Marmot, and Martin J Shipley Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of 19 000 men in the Whitehall study BMJ 2009; 339: b3513 [Abstract] [Full text]

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Error in On-line Routing to Data Supplement Table B

Robert S. Chapman   (19 September 2009)

Cardiovascular Risk Factors, Life Expectancy, Pulse Mass Index and Pulse Mass Pressure Product

Prof. Enrique J. Sánchez-Delgado, MD   (20 September 2009)

Curious choice of display for multiple factors

John R Lord   (28 September 2009)

Doubtful effect of cholesterol lowering

Uffe Ravnskov, Tore Schersten and Ralf Sundberg   (30 September 2009)

Life expectancy in relation to cardiovascular risk factors

Robert J Clarke, Martin J Shipley   (11 November 2009)

Re: Life expectancy in relation to cardiovascular risk factors

L Sam Lewis   (12 November 2009)

Error in On-line Routing to Data Supplement Table B 19 September 2009
Robert S. Chapman, Lecturer College of Public Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand Send response to journal: Re: Error in On-line Routing to Data Supplement Table B	Clicking on the link for Data Supplement Table B (Hazard ratios for mortality and life expectancy for smoking and dichotomous categories of risk factors) opens a different table that has no relation to this interesting and important article. There seems to have been a clerical error. Thank you in advance for rectifying this. Competing interests: None declared
Cardiovascular Risk Factors, Life Expectancy, Pulse Mass Index and Pulse Mass Pressure Product 20 September 2009
Prof. Enrique J. Sánchez-Delgado, MD, Internist-Clinical Pharmacologist, Director of Medical Education Hospital Metropolitano Vivan Pellas, Managua, Nicaragua Send response to journal: Re: Cardiovascular Risk Factors, Life Expectancy, Pulse Mass Index and Pulse Mass Pressure Product	Robert Clarke et. al. (BMJ 17 Sept. 2009) found that in middle age people, the cardiovascular risk factors like hypertension, cholesterol, smoking and others, like diabetes and body mass index, can shorten life expectancy (LE) by 10 to 15 years after age 50, and they recommend public health strategies to lower the levels of the main risk factors, together with more intensive medical treatment for ‘high risk’ sub-groups, including the use of medication that have proven efficacy and could improve life expectancy. Their findings agree with the known reduction of ca. 5 year LE in untreated hypertension and ca. 8 to 10 years in type 2 diabetes, morbid obesity, smoking or depression. At the other hand, the preventive measures and improved treatments have resulted in reduced mortality, longer life expectancy and more years with quality of life. Though some trends like increased number of obese population and younger persons with hypertension or diabetes, threatens to stop or even reverse the great advances already achieved. It is therefore of the highest importance to identify the younger patients, in their twenties or thirties, who are hypertensive or pre- hypertensive, diabetics or with metabolic syndrome, that could benefit with more aggressive preventive measures or appropriate medications, as well as cessation of cigarette smoking at age 30 years or earlier, which adds about 10 years of life expectancy that they would lose if they continued to smoke. Ten years ago (Lancet, 13 March 1999), we published that the Pulse Mass Index is a simple way for the preliminary identification of young patient with a high cardiovascular risk, when their Pulse Mass Index is over 1.2 and specially if over 1.3 The Pulse Mass Index is calculated as follows: Pulse or Resting Heart Rate (after at least 2 hours fasting) multiplied by the Body Mass Index and divided by 1730 as common denominator. Normal is a Pulse Mass Index of 1.0 or less (0.7 to 1.0). A Pulse Mass Index over 1.2 or 1.3 has a correlation with the Framingham Risk Score of 95% in people over 40 years old, but is more sensitive in younger persons, despite their Framingham RS being apparently normal because of their young age. The practical usefulness of the Pulse Mass Index helps us to identify the persons with high risk that could need more intensive preventive measures or appropriate drugs, after confirmation with the Framingham Risk Score and other appropriate tests. The Pulse Mass Index can also help us to identify younger patients with pre-hypertension or metabolic syndrome that could also benefit from intensive prevention, including medication. There is a close association of the PMI with the Metabolic Syndrome and it is also frequently elevated in overweigth or obese persons with hypertension in initial stadiums or in pre-hypertensive. The Pulse Mass Index is also the most simple and economical first clinical approach, followed by the Framingham RS for the risk evaluation in a large population of both men and women, and more so in the developing countries, where around 80% of all cardiovascular deaths occurs. In the last few years, almost a decade after our original publication, several studies have confirmed the importance of the pulse or resting heart rate, as well as the body mass index, the two components of the Pulse Mass Index, as cardiovascular risk factors of first range. Among others the studies: BEAUTIFUL, EUROPA, QRISK, Women Health Initiative (WHI), the Framingham Heart Study and the Framingham Offspring Study. The Pulse Mass Index is useful in two ways: 1.- For a preliminary, rapid, inexpensive, clinical evaluation of the cardiovascular risk, especially practical in younger people that could require an early prevention or medications, and 2.- To predict the potential benefit or risks of new cardiovascular, metabolic or other drugs. Lately, we are studying the idea to improve the Pulse Mass Index to form the Pulse Mass Pressure Product (PMPP), an extension of both, the Pulse Mass Index and the Pulse Pressure Product, which I think could give us as clinicians, a more exact initial evaluation of the global cardiovascular risk, of hypertension in early stadiums, pre-hypertension, metabolic syndrome and which patients should be treated early, either with intensive lifestyle interventions, or appropriate drugs, according to the patients’ characteristics, to prevent cardiovascular events or complications of hypertension in young or pre-hypertensive people. For instance, the Pulse Mass Pressure Product (PMPP) can be: 72 (RHR) x 24 (BMI) x 115 (SBP), which totals 198720 or round 200000 or (200 k) as normal or basic values. In the case of a young pre-hypertensive patient, if he had a PMPP of round 240 k (PMPP x 1.2), he could be a candidate for intensive lifestyle interventions. If he had a PMPP of round 260k (PMPP x 1.3), he could be a serious candidate for prevention with appropriate drugs. If he had a PMPP of round 300k (PMPP x 1.5), he could be a definite candidate for treatment with appropriate antihypertensive drugs. Something similar could apply for the metabolic syndrome and global cardiovascular risk. I invite interested colleagues to evaluate this idea and contact with me to collaborate in this study. Prof. Enrique Sánchez-Delgado, MD Internist-Clinical Pharmacologist Director of Medical Education Hospital Metropolitano Vivian Pellas Managua, Nicaragua Competing interests: None declared
Curious choice of display for multiple factors 28 September 2009
John R Lord, Professor of Primary Medical Care University of Huddersfield Send response to journal: Re: Curious choice of display for multiple factors	Clarke et al provide very helpful evidence. Their work suggests that the risk factors that matter for all cause mortality are in descending order of importance:- Smoking, employment, blood pressure, blood glucose and marital status, cholesterol and finally BMI. Yet when combining risk factors they report their first (smoking) plus third (blood pressure) plus fifth (cholesterol) against the effects of all risk factors. How much more helpful it would have been to compare the top four factors against all six. The size of this difference would help to establish how much attention to give BMI and cholesterol. Competing interests: None declared
Doubtful effect of cholesterol lowering 30 September 2009
Uffe Ravnskov, independent researcher Magle Stora Kyrkogata 9, 22350 Lund, Sweden, Tore Schersten and Ralf Sundberg Send response to journal: Re: Doubtful effect of cholesterol lowering	In their estimation of the life expectancy in the Whitehall cohort, Clarke et al claimed that the decline in cardiovascular mortality that has occurred in the UK population was partly attributable to changes in cholesterol concentrations.1 This statement can be questioned. Since a meta-analysis of the randomised and controlled cholesterol lowering trials performed up to 1992 did not find any effect on cardiovascular mortality,2 the alleged influence of cholesterol lowering must have been caused by the statins introduced a few years later. However, according to the mortality curves in their paper the decrease of vascular mortality started already in the sixties, and the slopes are unchanged from about 1980 up to today.      The authors’ conclusion that more intensive cholesterol lowering can result in further improvement in life expectancy is dubious as well. Recently Sachdeva et al. reported that the mean LDL cholesterol in 136,905 patients admitted because of an acute myocardial infarction was lower than normally.3 These authors also concluded that cholesterol lowering should be intensified, as did Al-Mallah et al. who came up with similar results.4 However, at a three-year follow-up, all cause mortality for those whose LDL cholesterol was below 105 mg/dl at admission was almost twice as high as those whose LDL cholesterol was higher.4      From the above we suggest that the observed reduction of cardiovascular mortality is rather the result of the increasing numbers of and quality of revascularization procedures than cholesterol lowering.  Clarke R, Emberson J, Fletcher A, Breeze E, Marmot M, Shipley MJ. Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of 19 000 men in the Whitehall study. BMJ 2009;339:b3513. doi: 10.1136/bmj.b3513. Ravnskov U. Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. BMJ 1992;305:15-9. Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J 2009;157:111-7 Al-Mallah MH, Hatahet H, Cavalcante JL, Khanal S. Low admission LDL-cholesterol is associated with increased 3-year all-cause mortality in patients with non ST segment elevation myocardial infarction. Cardiol J 2009;16:227-33. Competing interests: None declared
Life expectancy in relation to cardiovascular risk factors 11 November 2009
Robert J Clarke, Reader in Epidemiology and Public Health Medicine Clinical Trial Service Unit and Epidemiological Studies Unit, Martin J Shipley Send response to journal: Re: Life expectancy in relation to cardiovascular risk factors	The objectives of our recent report from the Whitehall study were to estimate life expectancy in relation to cardiovascular risk factors (1). In the 38-year follow-up of 19,019 middle aged men first examined in 1967- 1970, we estimated life expectancy in relation to smoking, blood pressure, and total cholesterol, separately and in combination in a risk score, also including body mass index, employment grade and diabetes mellitus/ glucose intolerance. The three main risk factors were selected for measurement in advance, as being modifiable risk factors that are causally related to cardiovascular disease (2). It would be prudent not to rank the risk factors associated with life expectancy to indicate their importance for disease prevention (3). Classification of participants on the basis of unequal groupings for smoking, diabetes and glucose intolerance and total cholesterol will preclude any such comparisons. Use of more extreme groups in a risk factor distribution will result in greater differences in life expectancy. Moreover, while smoking is causally related to both vascular and non-vascular mortality, total cholesterol is unrelated to non-vascular mortality (at least in part due to reverse-causality [4]). Despite substantial within-person variability in these risk factors (5), measurement of these risk factors on a single occasion at age 50 was associated with a 10 to 15 year shorter life expectancy. The results quantify the life-limiting effects of these risk factors and highlight the importance of having such risk factors measured at least once in middle age for prevention of cardiovascular disease. References 1) Clarke R, Emberson J, Fletcher A, Breeze E, Marmot M, Shipley M J. Life expectancy in relation to cardiovascular risk factors: 38 year follow-up of 19000 men in the Whitehall Study. BMJ 2009; 339: b 3513 doi: 104136/bmj.63513. 2) Rose G, Reid DD, Hamilton PJS, McCartney P, Keen H, Jarrett RJ. Myocardial ischaemia, risk factors and death from coronary heart disease. Lancet 1977;i: 105-9. 3) Lord JR. Curious display for multiple factors. BMJ (current issue). 4) Smith GD, Shipley MJ, Marmot M, Rose G. Plasma Cholesterol Concentration and Mortality: The Whitehall Study. JAMA 1992; 267: 70 - 76. 5) Clarke R, Shipley M, Collins R, Marmot M, Peto R. Underestimation of risk associations due to regression dilution in long-term follow-up of prospective studies. Am J Epidemiol 1999;150: 341-53. Competing interests: None declared
Re: Life expectancy in relation to cardiovascular risk factors 12 November 2009
L Sam Lewis, GP SA42 0TJ Send response to journal: Re: Re: Life expectancy in relation to cardiovascular risk factors	"measurement of these risk factors on a single occasion at age 50 was associated with a 10 to 15 year shorter life expectancy." Good Lord !! I really should steer clear of screening .. Competing interests: Worry versus Wellness