Revised MN 01-430, Aortic stiffness and coronary heart disease
Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients : A longitudinal study
Revised MN 01-430 R3, Septembre, 2001
Pierre BOUTOUYRIE et al.
Methods on line
Subjects and study design
The cohort included 1045 essential hypertensive patients with no overt cardiovascular disease or symptoms, who attended the outpatient hypertension clinic of Hôpital Broussais between April 1980 and December 1996, and had a measurement of arterial stiffness at baseline. None of these patients were referred for typical symptoms of CHD (or other cardiovascular disease). Among them, 350 (34%) were already treated with at least one antihypertensive drug at the time of the PWV measurement. The others were referred for clinical investigation before treatment. Demographic data with details of cardiovascular risk factors were collected on the day when PWV was measured. Diabetes (yes/no) and hypercholesterolemia (yes/no) were indicated by a previous diagnosis or the use of an oral hypoglycaemic agent or a cholesterol-lowering agent. Smoking status (yes/no) was defined as a current use. The procedures followed were in accordance with institutional guidelines.
Supine blood pressure was measured by a nurse at the right arm with a manual sphygmomanometer. After a 10-minute period, pressure was measured three times, and the mean of the last two measurements was calculated. The first and the fifth Korotkoff’s phases were used to define SBP and DBP. Pulse pressure was calculated as SBP-DBP.
Framingham risk score
A coronary disease prediction algorithm, based on the Framingham Heart Study, (Framingham risk score, FRS) was calculated for each patient 1. Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total, LDL, and HDL cholesterol categories 1. This simple coronary disease prediction algorithm using categorical variables has been reported to effectively predict multivariate CHD risk within 10 years in a middle-aged white population sample without overt cardiovascular disease 1.
PWV measurement
PWV, a classic index of arterial stiffness 7-8, was measured along the descending thoraco-abdominal aorta using the foot to foot velocity method, as previously published and validated 8. Briefly, waveforms were obtained transcutaneously over the right common carotid artery and the right femoral artery, and the time delay (t) was measured between the feet of the two waveforms. The distance (D) covered by the waves was assimilated to the distance measured between the two recording sites. PWV was calculated as PWV=D(meters)/t(seconds) 8.
Events
The follow-up period ended on December 31st 1996. All the 1045 patients’ files were consulted to collect every events, which were reported in anonymous short medical records. These short medical records were reviewed by 3 investigators who categorized morbid events separately and blindly as primary events. Patients in whom the first event was death were identified from the mortality records of the French Institut National de Statistiques et d'Etudes Economiques (INSEE), and causes of death were obtained from the death certificates provided by the Department of Mortality of INSERM (Institut National de la Santé et de la Recherche Médicale, Unit SC 8), as previously described 3,10. Causes of death were codified according to the International Classification of Disease. Coronary heart disease was defined as fatal and non fatal myocardial infarction, sudden death, coronary revascularization and documented angina pectoris. Other cardiovascular events in our cohort included strokes, newly discovered abdominal aortic aneurysm, new onset of peripheral arterial disease (defined as new onset of intermittent claudication, confirmed by angiography), hypertension-related nephrangiosclerosis (with biopsy diagnosis), and heart failure. Follow-up time was defined from the date of the baseline examination to the date of the first cardiovascular event or to the date of last contact free of cardiovascular disease.
Statistical analysis
The primary end-point of this study was the first fatal or non fatal CHD event during follow-up. A secondary endpoint was the occurrence of any fatal and non fatal primary cardiovascular events. The effects of classical risk factors on PWV were analyzed using a multivariate regression analysis. We used Cox regression analysis 14 to calculate the unadjusted and adjusted relative risks and 95 percent confidence intervals for CHD and all-cardiovascular events in relation to FRS and PWV levels (per 1 standard deviation (SD) increment of FRS and/or PWV). To identify independent predictors of CHD and all cardiovascular events, we used multivariate Cox regression analyses with stepwise selection. Variables included in multivariate models were PWV, and FRS or classical cardiovascular risk factors. Classical cardiovascular risk factors were age, gender, blood pressure, HR, hypercholesterolemia, diabetes, smoking and previous anti-hypertensive treatment. For each analysis, blood pressure parameters included either SBP and DBP or MBP and PP. The hazard ratio and the 95 percent confidence interval were calculated as appropriate.
We further established tertile ranges for FRS and PWV in our population, and we
obtained relative risks by comparing the frequency of the end point in patients in tertiles 2 and 3 with that in the reference tertile 1. We used multivariate conditional logistic-regression models to assess the contribution of each variable to the prognostic. Each was included as a continuous variable and in a separate analysis as a categorical variable (in which tertiles were used). To quantify the ability of PWV to detect the occurrence of cardiovascular or CHD events, we used receiver operating characteristics (ROC) curves, which express sensitivity as a function of specificity. All calculations were performed using the NCSS 2000 statistical package (J.L. Hintze, Kaysville, Utah).
1