Recurrent vertigo is a predictor of stroke in a large cohort of hypertensive patients.

OBJECTIVE: Dizziness is associated with hypertension but there are numerous other causes. The aims of the present study were to describe the characteristics and the clinical correlates of dizziness in a large cohort of hypertensive patients, and to test its prognostic value for all-cause, cardiovascular, and stroke mortality. METHODS: A total of 1716 individuals from the OLD-HTA Lyon's cohort of hypertensive patients recruited in the 1970s were categorized according to the absence or the presence of dizziness. The dizziness group was subdivided into vertigo and other dizziness excluding vertigo. RESULTS: Multiple regression analysis demonstrated that presence of dizziness was predicted by age, female sex, coronary artery disease, and the absence of microalbuminuria. During 30 years of follow-up, we observed 956 deaths, 508 of which with a cardiovascular cause, and 114 fatal acute strokes. In the multivariate Cox regression model, the presence of dizziness had no impact on the risk for all-cause mortality [hazard ratio 0.91; 95% CI (0.78-1.06)], cardiovascular mortality [hazard ratio 0.86; 95% CI (0.70-1.05)], or stroke mortality [hazard ratio 1.27; 95% CI (0.85-1.90)]. In an analysis of the different subgroups of dizziness, only vertigo had a prognostic impact. The increased risk was particularly marked on stroke death with a hazard ratio of 2.43 (95% CI 1.33-4.46) vs. patients without dizziness and 2.22 (95% CI 1.21-4.06) vs. patients with dizziness excluding vertigo. CONCLUSION: Hypertensive patients with dizziness did not have a high-risk profile at baseline, but those with vertigo must be carefully followed over years because of the higher stroke mortality.

Aortic atherosclerosis is a key modulator of the prognostic value of postural blood pressure changes.

BACKGROUND AND AIMS: Orthostatic blood pressure decrease or increase has been related to cardiovascular events in hypertensive patients. Large blood pressure changes after orthostatic stress are associated with autonomic and neurohormonal abnormalities; aortic atherosclerosis (ATS) may also play a role. METHODS: We investigated the interaction of ATS on the prognostic value of postural blood pressure changes. In a cohort of 958 hypertensive patients with an aortography (mean ± standard deviation age 44 ± 11 years, 61% men, mean blood pressure 182/110 mmHg), blood pressure was measured after 10 min of rest in the supine position. Systolic blood pressure (SBP) was also measured in standing position, 1 min after the supine position. Blood pressure changes were calculated as supine SBP minus standing SBP and analyzed as absolute or arithmetic means. ATS was assessed using an aortography score. RESULTS: After 15 years of follow-up, 280 all-cause and 167 cardiovascular deaths occurred. In a multivariable Cox regression analysis adjusted for major cardiovascular risk factors and stratified according to ATS status, SBP changes were statistically associated with all-cause and cardiovascular mortality only in the presence of ATS: tertile 3 versus 1, 2.99 (1.37-6.49) and 4.08 (1.55-10.72) respectively, tertile 3 versus 2, 2.89 (1.29-6.46) and 4.82 (1.79-12.98), respectively (p for interaction: 0.003 for all-cause and 0.003 for cardiovascular mortality) for absolute changes. The hazard associated with the magnitude of SBP changes was more important than that associated with its direction. CONCLUSIONS: The prognostic significance of postural SBP changes is markedly influenced by ATS in hypertensive patients.

Association Between Protein Intake and Mortality in Hypertensive Patients Without Chronic Kidney Disease in the OLD-HTA Cohort.

Protein intake may have some benefits on reducing blood pressure and cardiovascular events, but their effects are still debated. The objective of this study was to test the prognostic value of protein intake assessed by 24-hour urinary urea in a cohort of hypertensive patients with preserved renal function. A total of 1128 hypertensive patients were followed according to tertile of protein intake adjusted for ideal body weight: <0.70, 0.70 to 0.93, and >0.93 g/kg. Baseline characteristics (mean±standard deviation) were age 45.1±13.2 years, systolic/diastolic blood pressure 185±32/107±20 mm Hg, and estimated glomerular filtration rate 82±32 mL/min. After 10 years of follow-up, 289 deaths occurred, 202 of which were of cardiovascular cause. After adjustment for major cardiovascular risk factors, patients in the second and third tertiles of protein intake had a decreased risk of all-cause death (hazard ratio [95% confidence interval], 0.71 [0.56-0.91]) and cardiovascular death (0.72 [0.54-0.96]), but not of stroke death (0.72 [0.41-1.28]) in comparison to patients in the low protein intake tertile. Normal-high protein intake was associated with a better outcome in a subset of the population: younger patients, low salt intake, without aortic atherosclerosis, or previous cardiovascular events (Pinteraction<0.10 for all). Hypertensive patients having a protein intake >0.7 g/kg ideal body weight, particularly those at low risk, had lower all-cause and cardiovascular mortality rates. Physicians may encourage hyper tensive patients to have normal or high protein diet in addition to low salt consumption, moderate alcohol consumption, and regular physical activity.

The Paradoxical Significance of Headache in Hypertension.

BACKGROUND: The cardiovascular prognostic value of various types of headache, particularly migraine, in the general population remains controversial. The aim of the present study was to assess their prognostic value for all-cause, cardiovascular and stroke mortalities in hypertensive patients. METHODS: A total of 1,914 hypertensive individuals were first categorized according to the absence or presence of headache and thereafter according to the 3 subtypes of headache: migraine, daily headache, and other headache. RESULTS: Multiple regression analysis demonstrated that all headache types were predicted by gender (women), diastolic blood pressure, absence of diabetes, secondary hypertension, and a trend for severe retinopathy. After 30 years of follow-up, 1,076 deaths were observed, 580 of whom were from cardiovascular cause and 97 from acute stroke. In a multivariable Cox model adjusted for major confounders, patients having headache had a decreased risk for all-cause mortality (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.73-0.93) and cardiovascular mortality (HR 0.80; 95% CI 0.68-0.95), but not for stroke mortality (HR 1.00; 95% CI 0.70-1.43). When considering only patients with headache, "daily headache" had a nonsignificant better prognostic value for all-cause and cardiovascular mortality than "other headache" (HR 0.83; 95% CI 0.68-1.01; HR 0.89; 95% CI 0.69-1.16, respectively) and "migraine" (HR 0.85; 95% CI 0.65-1.11; HR 0.78; 95% CI 0.55-1.10, respectively). CONCLUSION: Presence of nonspecific headache in hypertensive patients has a paradoxical significance in that it is associated with a high-risk profile but does not result in a worse prognosis over the long term.

Cumulative Effects of Several Target Organ Damages in Risk Assessment in Hypertension.

BACKGROUND: The prognostic value of screening multiple target organ damages (TODs) in hypertensive subjects has not been extensively studied. We estimated the prognostic value of considering 3 TODs in estimating the 10-year survival in hypertensive subjects. METHODS: At baseline 1,848 out of a cohort of 1,963 hypertensive patients had a previous cardiovascular disease (CVD) or assessments of 3 TODs: Modification in Diet in Renal Disease (MDRD) <60ml/min or albuminuria >300mg/day, Sokolow index >3.5 mV, and advanced hypertensive retinopathy (grades 3 and 4 of Keith-Wagener-Barker classification). The cohort was divided into 5 groups: 0 TOD (N = 978), 1 TOD (N = 308), 2 TODs (N = 94), 3 TODs (N = 30), and previous CVD (N = 438). RESULTS: After 10 years of follow-up, we observed 418 deaths of which 254 from cardiovascular cause. The adjusted hazard ratios for the major cardiovascular risk factors showed a progressive risk associated with the number of TODs. For all-cause death, the hazard ratios [95% confidence intervals] vs. 0 TOD of the other 4 groups were 1.91 [1.39-2.63], 1.99 [1.28-3.10], 4.33 [2.42-7.72], and 3.09 [2.35-4.05], respectively. For cardiovascular death, the hazard ratios [95% confidence intervals] were of the same order of magnitude: 2.14 [1.38-3.32], 2.12 [1.15-3.89], 4.22 [1.83-9.72], and 4.24 [2.95-6.11], respectively. CONCLUSIONS: Our results indicate that hypertensive patients with several TODs had a worst outcome. Thus, it seems important to screen for multiple TODs in hypertension; especially check for severe hypertensive retinopathy in patients with left ventricular hypertrophy (LVH) and renal damage.

R wave in aVL lead: an outstanding ECG index in hypertension.

OBJECTIVES: The voltage of R wave in lead aVL (RaVL) seems to be more tightly correlated with left ventricular mass and cardiovascular events than any other ECG criterium of left ventricular hypertrophy. We hypothesized that RaVL could be an independent predictor of all-cause and cardiovascular death in hypertensive individuals. METHODS: The baseline clinical and biological variables as well as ECG recordings were analyzed in a prospective cohort of 589 hypertensive individuals. RESULTS: After 10 years of follow-up, we observed 95 deaths of which 53 had a cardiovascular cause. The optimal RaVL voltages to predict all-cause and cardiovascular mortality were 0.8 and 0.6  mV, respectively. In a multivariate adjusted Cox model, having an RaVL voltage superior to these cutoffs was associated with increased risks of all-cause death [hazard ratio: 2.04, 95% confidence interval (CI): (1.30-3.22)] and of cardiovascular death [hazard ratio: 2.89, 95% CI: (1.47-5.68)]. In the whole cohort and with the same adjusted Cox regression model, each 0.1  mV increment would increase the risk of all-cause death by 1.07 times [95% CI: (1.02-1.12)] and that of cardiovascular death by 1.13 times [95% CI: (1.06-1.20)]. After excluding in turn patients with positive Sokolow index, Cornell voltage, or Cornell product, the results remained statistically significant, meaning that RaVL was still able to pick-up high-risk patients when other classical and more sophisticated indices were not observable. CONCLUSION: The present results strengthen previous reports that demonstrated a strong role of RaVL voltage in risk stratification in hypertension.

Diastolic blood pressure, aortic atheroma, and prognosis in hypertension: new insights into a complex association.

OBJECTIVES: Our study aimed at determining the interaction between the prognostic value of diastolic blood pressure (DBP) and aortic atherosclerosis (ATS). BACKGROUND: With aging, equal systolic blood pressures (SBPs) become associated with low DBPs; i.e., high pulse pressures (PPs) become associated with a high risk of cardiovascular death. This association is usually ascribed to aortic stiffening with age but the precise impact of low DBP per se is yet uncertain. METHODS: 938 hypertensive patients recruited in the seventies had an aortic ATS score at pretreatment aortography. All-cause and cardiovascular deaths were assessed 20 years later. The prognostic values of DBP and SBP were assessed by a multivariate Cox regression model and their interactions with ATS examined. RESULTS: In the presence of ATS, an increase of 10 mmHg in DBP was associated with a protective effect: hazard ratios 0.84 [0.72-0.99] for cardiovascular death and 0.88 [0.78-1.00] for all-cause death. However, in the absence of ATS, DBP had no prognostic value: hazard ratios 1.05 [0.89-1.23] for cardiovascular death and 0.99 [0.88-1.11] for all-cause death (p for interaction: 0.061 and 0.087, respectively). No interaction was found between SBP and ATS (p for interaction > 0.40). CONCLUSIONS: The prognostic values of DBP and aortic atheroma are not superimposable; yet, they are tightly connected: a low DBP is disadvantageous only in the presence of a pathologic aorta. Aortic atherosclerosis may explain, at least partly, in some high risk populations, the J-shape of the already reported DBP-outcome relationship.

Effect modification of aortic atheroma on the prognostic value of heart rate in hypertension.

BACKGROUND: Although some epidemiological studies have advocated a prognostic value of heart rate (HR) in hypertensive patients, the influence of vascular damages on this prognostic value has not been tested yet. METHODS: HRs were collected by pulse palpation in 1204 primary hypertensive patients in sinus rhythm without cardiac-slowing drugs. Aortic damages were assessed by aortography, whereas cardiac disease was assessed by medical history, symptoms and electrocardiogram. RESULTS: In a multivariable Cox model adjusted for major confounders, HR was of prognostic significance for all-cause [hazard ratio 1.12 (1.06-1.19) for 10 bpm increment and 1.39 (1.18-1.64) for HR ≥82 vs. <82 bpm] and cardiovascular death [hazard ratio 1.10 (1.02-1.20) for 10 bpm increment and 1.37 (1.09-1.72) for HR ≥82 vs. <82 bpm] after 35 years of follow-up. This association was particularly manifested at 15 years of follow-up. At that time, with the same multivariable survival model, the association between HR and cardiovascular death was stronger in patients with aortic atheroma [2.76 (1.47-5.18) for an HR ≥82 vs. <82 bpm] than in patients without [hazard ratio 1.36 (0.76-2.43) for an HR ≥82 vs. <82 bpm, P for interaction = 0.054]. Similarly, the association between HR and cardiovascular death was stronger in patients with an overt cardiac disease than those without (P for interaction = 0.044). CONCLUSION: In hypertensive patients, the prognostic significance of HR for cardiovascular outcome is modulated by the presence of aortic atherosclerosis or cardiac disease. This should prompt us to a thorough examination of cardiovascular damages in hypertensive patients when HR is elevated.

Outcome associations of carotid-femoral pulse wave velocity vary with different measurement methods.

BACKGROUND: The impact of various methods of travel distance estimation on the prognostic value of pulse wave velocity (PWV) and on the adequacy of cut-offs has never been addressed within a single population of hypertensive patients. METHODS: Four carotid-femoral PWVs were calculated from four different travel distances (Direct, Real, Subtracted, and Estimated) divided by the same travel time in 426 hypertensives (mean age 51.2 ± 13.8 years, mean systolic blood pressure 155.6 ± 21.1 mm Hg). The incidence of death from any cause and major cardiovascular events was studied. PWV predictive accuracies were determined using C-index analysis. Hazard ratios (HRs) associated with specific values of PWV were determined with Cox model analyses using cubic splines. RESULTS: Mean PWV ranged from 8.3 ± 2.3 m/s for the Subtracted one to 11.6 ± 3.0 m/s for the Direct one (P < 0.001). When included as continuous variables in a Cox model, the four PWVs were significantly associated with outcome (all P < 0.001), and had similar C-index (0.608-0.617). In multivariable analysis, the HR calculated for a Direct PWV of 12 m/s was neutral (HR = 1.02). In contrast, the same analysis provided HR ranging from 1.79 to 2.90 with the other PWVs. CONCLUSIONS: Different travel distances markedly impact PWV values and prognostic cut-offs. PWV cut-offs should consequently be ascertained jointly with the method of measurement used. There is an urgent need for standardization of PWV assessment before implementing this parameter in the routine management of hypertensives.

N-terminal pro-brain natriuretic peptide: a powerful predictor of mortality in hypertension.

Natriuretic peptides are controregulatory hormones associated with cardiac remodeling, namely, left ventricular hypertrophy and systolic/diastolic dysfunction. We intended to address the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in hypertension. We prospectively studied the relationship between plasma NT-proBNP and all-cause mortality in 684 hypertensive patients with no history or symptoms of heart failure referred for hypertension workup in our institution from 1998 to 2008. After a mean duration of 5.7 years, we observed 40 deaths (1.04 deaths per 100 patients per year). After adjustment for traditional cardiovascular risk factors, including ambulatory blood pressure and serum creatinine, the risk for all-cause mortality more than doubled with each increment of 1 log NT-proBNP (hazard ratio: 2.33 [95% CI: 1.36 to 3.96]). The risk of death of patients with plasma NT-proBNP≥133 pg/mL (third tertile of the distribution) was 3.3 times that of patients with values<50.8 pg/mL (first tertile; hazard ratio: 3.30 [95% CI: 0.90 to 12.29]). This predictive value was independent of, and superior to, that of 2 ECG indexes of left ventricular hypertrophy, the Sokolov-Lyon index and the amplitude of the R wave in lead aVL. In addition, it persisted in patients without ECG left ventricular hypertrophy, which allowed refining risk stratification in this relatively low-risk patient category. In this large sample of hypertensive patients, plasma NT-proBNP appeared as a strong prognostic marker. This performance, together with the ease of measurement, low cost, and widespread availability of NT-proBNP test kits, should prompt a wide use of this marker for risk stratification in hypertension.

Effect of abdominal aortic grafts on aortic stiffness and central hemodynamics.

Graft-prosthesis and stentgraft placements are effective modalities for treating abdominal aortic aneurysm, but related changes in arterial stiffness are not well established. The present study sought to assess aortic stiffness after aneurism repair by measuring pulse wave velocity (PWV). The graft-related variation of carotid-femoral PWV was compared with that of carotid-radial PWV, the latter being unaffected by vascular treatment. The secondary objective was to evaluate potential differences between graft-prosthesis and stentgraft in terms of aortic stiffness and augmentation index, a composite indicator integrating wave reflexion. Fifty patients were included (39 had a graft-prosthesis and 11 had a stentgraft). In the whole group and after a median postoperative follow-up of 47 days, carotid-femoral PWV increased by +1.0 m/s [-12.3, +10.3], while carotid-radial PWV slightly decreased by -0.3 m/s [-4.4; +3.5] (P = 0.001). The effect of the type of prosthesis on the PWV was not significant. Nevertheless, the augmentation index increased after stentgraft implantation (+4% [-10; +17]) and decreased after graft-prosthesis placement (-8.5% [-47; +17]) (P < 0.01). This difference was not explained by a heart rate or a treatment effect and was likely attributable to the prosthesis per se. This study demonstrates the impact of aortic grafts on aortic stiffness. Besides, it suggests that stentgraft increases reflected waves more than graft-prostheses. These changes of vascular properties may influence the outcomes after surgery.

N-terminal pro-brain natriuretic peptide--a promising biomarker for the diagnosis of left ventricular hypertrophy in hypertensive women.

INTRODUCTION: No agreement has been reached regarding the best strategy to detect left ventricular hypertrophy (LVH). This study examined the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of LVH in hypertensive patients and the potential factors that may influence its diagnostic performance. METHODS: The global accuracy of NT-proBNP in diagnosing LVH was assessed using a receiver-operating characteristic (ROC) curve. The influence of patients' characteristics on test accuracy was studied with a ROC regression based on a probit model. Ninety-three subjects were included. All had NT-proBNP measured and underwent electrocardiography and echocardiography, with calculation of the left ventricular mass index (LVMI). RESULTS: The diagnostic performance of NT-proBNP in LVH varied slightly depending on the indexation mode of LVMI. In cases of body surface area indexation, the area under the ROC curve of 81.6% suggested a good performance. The accuracy of the marker was significantly higher in women than in men (p<0.0001). There were no significant effects of age, treatment, body mass index, left ventricular mass index, 24-h systolic blood pressure, or creatinine clearance on the test performance. Slight differences were observed when an indexation to height(2.7) instead of body surface area was used. CONCLUSIONS: The present results may lead to a new strategy for risk stratification in hypertension: in women, NT-proBNP alone or preferably in combination with electrocardiography seems sufficient to confirm or exclude diagnosis of LVH. In men, echocardiography would only be needed in cases of negative electrocardiography and NT-proBNP test.

Insulin resistance and plasma triglyceride level are differently related to cardiac hypertrophy and arterial stiffening in hypertensive subjects.

OBJECTIVE: The frequent association between the type 2 diabetes mellitus and cardio-vascular diseases suggests that metabolic factors may contribute to cardio-vascular remodeling. The aim of our study was to examine the relationships between left ventricular posterior wall thickness (LVPWT), pulse wave velocity (PWV), and the metabolic abnormalities of insulin resistance syndrome, in hypertensive patients. METHODS: In 227 consecutive hypertensives, we examined the relationships between LVPWT, PWV, and metabolic factors: plasma glucose, insulin, total cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides levels as well as the homeostasis model assessment of insulin resistance (HOMA). The Pearson correlation coefficient and multiple regression analysis (including age, gender, body mass index, and 24-hour systolic blood pressure) were used as statistical tests. RESULTS: In univariate analysis, glucose, HDL-cholesterol, and triglycerides levels were related to LVPWT (r = 0.19, p < 0.05; r = -0.26, p < 0.001; r = 0.31, p < 0.001, respectively); all metabolic variables, except HDL-cholesterol, correlated to PWV (plasma glucose r = 0.25, p < 0.001; total cholesterol r = 0.22, p < 0.01; triglycerides r = 0.20, p < 0.01; insulin r = 0.19, p < 0.01; HOMA r = 0.27; p < 0.001). In the multivariate model, plasma triglycerides remained correlated with LVPWT (beta = 0.19, p < 0.02) independently of systolic blood pressure, plasma aldosterone, and normetanephrine. Only HOMA and insulin level remained associated with PWV (beta = 0.14; beta = 0.13 respectively, p < 0.05). CONCLUSIONS: These data suggest that among typical metabolic abnormalities of insulin resistance syndrome, plasma triglycerides, and insulin as well as degree of insulin resistance may contribute to cardiac hypertrophy and arterial stiffening independently of hemodynamic and hormonal factors.

Pheochromocytoma unmasked by amisulpride and tiapride.

OBJECTIVE: To describe the unmasking of pheochromocytoma in a patient treated with amisulpride and tiapride. CASE SUMMARY: A 42-year-old white man developed acute hypertension with severe headache and vomiting 2 hours after the first doses of amisulpride 100 mg and tiapride 100 mg. Both drugs were immediately discontinued, and the patient recovered after subsequent nicardipine and verapamil treatment. Abdominal ultrasound showed an adrenal mass, and postoperative histologic examination confirmed the diagnosis of pheochromocytoma. DISCUSSION: Drug-induced symptoms of pheochromocytoma are often associated with the use of substituted benzamide drugs, but the underlying mechanism is unknown. In our case, use of the Naranjo probability scale indicated a possible relationship between the hypertensive crisis and amisulpride and tiapride therapy. CONCLUSIONS: As of March 24, 2005, this is the first reported case of amisulpride- and tiapride-induced hypertensive crisis in a patient with pheochromocytoma. Physicians and other healthcare professionals should be aware of this potential adverse effect of tiapride and amisulpride.

Significance of urinary angiotensinogen in essential hypertension as a function of plasma renin and aldosterone status.

OBJECTIVE: This study was performed to test the significance of urinary angiotensinogen (UAGT) in essential hypertensive patients stratified as a function of plasma renin and aldosterone. METHODS AND RESULTS: A sample of 248 essential hypertensives, investigated under their usual sodium diet and either off-medication or under a standardized treatment, was separated into two groups on the basis of upright plasma active renin and aldosterone medians. Patients with plasma active renin and aldosterone below medians are referred to as the low renin-aldosterone essential hypertensive group (LRA-EH). Others subjects are defined as other essential hypertensives (O-EH). Blood pressure (BP) was recorded by 24-h ambulatory monitoring. UAGT was measured by a specific enzyme-linked immunosorbent assay for total angiotensinogen. Because UAGT was markedly increased in the presence of overt proteinuria (>/= 300 mg/24 h), proteinuric patients (n = 29) were excluded from subsequent analyses. UAGT was a significant predictor of systolic and diastolic BP in LRA-EH females (P < 0.01 and P = 0.05, respectively) but not in males. By contrast, urinary sodium excretion (P < 0.001) and maintenance of treatment (P = 0.002) were significant predictors of systolic BP in males. These correlations were not observed in O-EH, whether males or females. CONCLUSIONS: In the present study, UAGT stands as a strong predictor of BP in women with low plasma renin/aldosterone, suggesting an involvement of the tubular renin-angiotensin system in these subjects. Higher sodium intake or the need to maintain treatment may account in part for the lack of a similar relationship in males.

A1166C polymorphism of angiotensin II type 1 receptor, blood pressure and arterial stiffness in hypertension.

OBJECTIVE: To study the association of the AC polymorphism of angiotensin II type 1 receptor gene (AGTR1) with blood pressure and central arterial stiffness in a population of hypertensive patients referred to hospital for further work-up. METHODS: One hundred and eighty-five patients, referred to our department from April 1998 to February 2002, were included. Blood pressure was measured by conventional and 24-h ambulatory methods, and arterial stiffness by carotid-femoral pulse wave velocity (PWV) determination. Genotyping for the AGTR1 AC polymorphism was performed by polymerase chain reaction. RESULTS: AGTR1 AC polymorphism was not associated with systolic or diastolic blood pressure, measured either by conventional (P=0.89 and P=0.67, respectively) or by 24-h ambulatory (P=0.57 and P=0.56, respectively) methods. Conversely, this polymorphism was significantly associated with PWV (P=0.006) and had a dose-allele effect, PWV increasing with the number of A alleles (10.6 +/- 2.4 m/s in CC, 11.9 +/- 2.5 m/s in AC and 12.7 +/- 2.7 m/s in AA patients, P=0.002). Multiple regression analysis showed that AC polymorphism was still independently associated with PWV (P=0.01) and was the third most important determinant of PWV after age (P <0.0001) and 24-h mean blood pressure (P <0.0001). CONCLUSION: In our study population, central arterial stiffness assessed by PWV was significantly and independently associated with the AC polymorphism, increased PWV being associated with the presence of the A allele. Further investigations are required for identification of the underlying mechanisms.

Heart rate: an important confounder of pulse wave velocity assessment.

Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave velocity (PWV) is an index of arterial stiffness, and its prognostic value has been repeatedly emphasized. The purpose of the present study was to assess the effect of heart rate (HR) on PWV. Twenty-two subjects with a mean age of 77.8+/-8.4 (SD) years and permanent cardiac pacing were studied. In each subject, PWV was measured at 5 different pacing frequencies in the same session (60, 70, 80, 90, 100 bpm), the order of the various frequencies being randomly determined. Furthermore, to test the reproducibility, a repeat measurement of PWV was obtained in one randomly selected frequency. Blood pressure (BP) was measured by conventional means at each pacing frequency. PWV appeared fairly reproducible because no significant difference was disclosed between the 2 measurements obtained at the same HR level (P=0.5) and both measurements were strongly correlated (r=0.87, P<0.001). No significant BP variation was observed during pacing. There was a highly significant effect of HR on PWV estimated by a one-way, within-subjects analysis of variance (P=0.01). This study demonstrates that HR is an important factor in the intraindividual variation of PWV in elderly subjects. This raises methodological concern about the measurement of this parameter. Standardizing PWV for HR level seems mandatory if one wants to interpret PWV changes in clinical trials or in the follow-up of patients.