Elisabeth J. Balkestein

Non-invasive assessment of local arterial pulse pressure : comparison of applanation tonometry and echo-tracking

Objectives Pulse pressure is not constant throughout the arterial tree. Use of pulse pressure at one arterial site as surrogate for pulse pressure at another arterial site may be erroneous. The present study compares three non-invasive techniques to measure local pulse pressure: (i) internally calibrated readings from applanation tonometry, (ii) alternative calibration of pressure waves obtained with applanation tonometry and (iii) alternative calibration of arterial distension waves obtained with echo-tracking. Alternative calibration assumes mean and diastolic blood pressure constant throughout the large artery tree. Design and methods Study 1 used invasive measurements in the ascending aorta as a reference method and internally calibrated tonometer readings and alternatively calibrated pressure waves at the common carotid artery as test methods. Study 2 used alternatively calibrated pressure waves as a reference method and alternatively calibrated distension waves and internally calibrated applanation tonometer readings as test methods. Results In study 1, pulse pressure from internally calibrated tonometer readings was 10.2 ± 14.3 mmHg lower and pulse pressure from alternatively calibrated pressure waves was 1.8 ± 5.2 mmHg higher than invasive pulse pressure. Pulse pressure from calibrated distension waves was 3.4 ± 6.9 mmHg lower than pulse pressure from alternatively calibrated pressure waves. According to British Hypertension Society criteria, pulse pressure from the internally calibrated tonometer achieved grade D and pulse pressure from alternatively calibrated pressure waves achieved grade A. Pulse pressure from calibrated distension waves achieved grade B when alternatively calibrated pressure waves were used as a reference method. Conclusions Pulse pressure obtained from alternatively calibrated tonometer-derived pressure waves and echo-tracking-derived distension waves demonstrates good accuracy. Accuracy of pulse pressure from internally calibrated applanation tonometer readings at the carotid artery is poor.

Obesity is associated with increased arterial stiffness from adolescence until old age.

Objective To our knowledge, only two previous studies have investigated the age dependence of the relationship between the characteristics of large arteries and excessive body weight. We therefore investigated whether the relationship between arterial stiffness and body mass index (BMI) was consistent across an age range from 10 to 86 years. Methods Using a cross-sectional population-based design, we randomly recruited 1306 individuals (median age 43.9 years; 50.5% women). Using a wall-tracking ultrasound system, we measured the properties of the carotid, femoral and brachial arteries and carotid–femoral pulse wave velocity. We analysed men and women separately while adjusting for significant covariates, including age, mean arterial pressure, heart rate, current smoking, alcohol intake and use of antihypertensive drugs. Results Before and after adjustment, arterial diameter increased with BMI in all territories, with an opposite trend for arterial distensibility. In men and women, the relationships of brachial and femoral properties with BMI were consistent across the whole age range. In men and women, carotid distensibility decreased more with BMI at young than old age. In middle-aged and older women, but not in men of any age, pulse wave velocity increased with higher BMI. Conclusions Across a wide age range, the diameter and stiffness of muscular arteries increased with higher BMI. In elastic arteries, the relationship between arterial stiffness and BMI was more complex and varied with sex and age. The mechanisms underlying the influence of adiposity on the properties of muscular and elastic arteries and the reversibility of these associations by weight reduction at young age need further clarification.

Brachial Pressure–Independent Reduction in Carotid Stiffness After Long-Term Angiotensin-Converting Enzyme Inhibition in Diabetic Hypertensives

Hypertension and diabetes are associated with an increased arterial stiffness. A direct blood pressure–independent effect of angiotensin-converting enzyme inhibitors on arterial stiffness has never been unequivocally demonstrated. In this mechanistic study, we used an experimental design in which patients responding to 1 month treatment with 4 mg perindopril were randomized double-blind to either 4 mg perindopril or 8 mg perindopril for 6 months. We determined carotid distensibility with echotracking and applanation tonometry at baseline and after the 7-month treatment period in 57 essential hypertensive patients with type 2 diabetes (age 63±7 years). We monitored ambulatory blood pressure at baseline and after treatment. After 7 months treatment, 24-hour ambulatory blood pressure significantly decreased, with no significant difference between 4 mg and 8 mg perindopril. Carotid distensibility increased more after 8 mg perindopril compared with 4 mg perindopril (8 mg: from 13.1±5.9 to 16.0±6.7 kPa−1×10−3; 4 mg: from 13.2±5.2 to 12.7±5.9 kPa−1×10−3; ANOVA, dose-period interaction, P<0.05). Carotid internal diameter and elastic modulus were significantly lower after 8 mg perindopril compared with 4 mg perindopril, independent of blood pressure reduction. These results indicate a dose-dependent and blood pressure–independent reduction in carotid stiffness under chronic treatment with an angiotensin-converting enzyme inhibitor. They suggest that arterial distensibility was increased through an inward remodeling, leading to a reduction in wall stress, thus reducing elastic modulus. They also suggest that long-term administration of high doses (8 mg) of perindopril is required to improve carotid structure and function in hypertensive patients with type 2 diabetes.

The effect of weight loss with or without exercise training on large artery compliance in healthy obese men.

BACKGROUND Obesity is an independent risk factor for cardiovascular morbidity and mortality. Large artery compliance is thought to be associated with cardiovascular risk. The effect of weight loss on large artery compliance is not yet clarified. OBJECTIVE To investigate the effect of weight loss, with or without exercise, on vessel wall properties in healthy obese men. DESIGN This was a pair-matched randomized intervention study. All subjects were on an energy-restricted diet. One subject from each pair was also on an exercise programme. Measurements were performed before and at the end of the study period. The study lasted for 3 months. METHODS The vessel wall properties of the brachial and common carotid artery were assessed using a vessel wall movement detector system in combination with applanation tonometry. RESULTS The mean body mass index was 32.3+/-0.4 kg/m2 and decreased (P < 0.001) to 27.6+/-0.4 kg/mm2 during the study. The mean blood pressure decreased (P < 0.001) by 6%. At operating pressures, carotid artery distensibility was 27.5+/-1.7 x 10(-3)/kPa at the start of the study and 31.1+/-1.8 x 10(-3)/kPa (P < 0.04) at the end of the study. Brachial and carotid artery compliances were 0.11+/-0.01 and 1.35+/-0.08 mm2/kPa at the start of the study and tended to increase to 0.12+/-0.001 (P = 0.06) and 1.48+/-0.08 mm2/kPa (P = 0.057), respectively, at the end of the study. Isobaric compliance did not change. The diet-and-exercise group did not differ statistically from the only-diet group in the effects on weight loss, blood pressure and arterial compliance. CONCLUSION This study shows that weight loss increased carotid artery distensibility at operating pressures, but not under isobaric conditions. This increase is probably due to the decrease in blood pressure. The addition of exercise did not result in an additional effect within 3 months.

Carotid and femoral intima-media thickness in relation to three candidate genes in a Caucasian population

Background In a Caucasian population, the prevalence and incidence of hypertension, renal function and large artery stiffness were significantly correlated with polymorphisms in the genes encoding the angiotensin-converting enzyme (ACE I/D), aldosterone synthase (− C344T) and the cytoskeleton protein α-adducin (Gly460Trp). Objective This study investigated intima–media thickening, a precursor of atherosclerosis, in relation to these genetic polymorphisms. Methods Carotid and femoral intima–media thickness were assessed with a wall-track system in 380 subjects enrolled in a population study. Subjects were genotyped for the presence of the ACE D, aldosterone synthase − 344T and α-adducin 460Trp alleles. The statistical analysis allowed for confounders, interactions among genes, and the non-independence of the phenotypes within families. Results The sample included 188 men (49.5%). Mean age was 39.8 years. Intima–media thickness of the carotid and femoral arteries averaged 575 and 719 μm, respectively. Intima–media thickness of the femoral–but not carotid–artery increased with the number of ACE D alleles. The effect of ACE genotype on femoral intima–media thickness was confined to carriers of the 460Trp allele and the − 344T allele. Expressed as a percentage of the population mean, the mean differences between II and DD homozygotes averaged 13.4% (95% CI 5.6–21.2%) in all subjects, 21.2% (8.0–34.5%) in carriers of the 460Trp allele, 15.4% (4.1–26.8%) in carriers of the − 344T allele, and 25.2% (10.7–39.7%) if the 460Trp and − 344T alleles were both present. Conclusion This study shows that a relationship exists between the intima–media thickness of the large muscular femoral artery and the ACE gene. This relationship is only apparent in the presence of either the α-adducin 460Trp or the aldosterone synthase −344T allele. These findings may have clinical implications for the assessment of genetic cardiovascular risk.

Is it possible to develop drugs that act more selectively on large arteries

BACKGROUND Patients with high pulse pressures have an increased risk for cardiovascular events. Drugs that selectively decrease high pulse pressure may be of interest for these patients. Such drugs have a more pronounced effect on large arteries than on resistance vessels. OBJECTIVE To compare the selectivity to large arteries of the new nitric oxide donor sinitrodil with the classic nitrate isosorbide dinitrate in healthy young men in order to investigate whether it is possible to develop drugs that act more selectively on large arteries. DESIGN The study had a double-blind, 5-way cross-over design. In randomized order, subjects received a single oral dose of 10 mg sinitrodil, 20 mg sinitrodil, 40 mg sinitrodil, isosorbide dinitrate and placebo. Measurements were performed before and 45 min after administration of the drugs. Between each drug administration, at least 3 days of wash-out was allowed. METHODS The effects of the drugs on large arteries and resistance vessels were assessed by their effects on brachial artery compliance and total peripheral resistance, respectively. RESULTS Brachial artery compliance increased gradually with increasing doses of sinitrodil (by 10, 20 and 27% with 10, 20 and 40 mg sinitrodil, respectively). Total peripheral resistance index decreased with isosorbide dinitrate (by 11%) and 40 mg sinitrodil (by 7%), while it remained unchanged with 10 mg and 20 mg sinitrodil. CONCLUSIONS The results of this study show that it may be possible to develop drugs with a higher selectivity for large arteries. Such drugs may be good candidates to decrease high pulse pressure without substantially decreasing mean and diastolic blood pressures.

THE METABOLIC SYNDROME AND CAROTID INTIMA-MEDIA THICKNESS IN RELATION TO THE PARATHYROID HORMONE TO 25-OH-D3 RATIO IN A GENERAL POPULATION: PP.7.265

Objective: Parathyroid hormone (PTH) and vitamin D interactively regulate calcium fluxes across membranes, and thereby modulate insulin sensitivity, blood pressure and arterial calcification. We hypothesized that lower calcium intake as reflected by circulating PTH and 25-OH-D3 might be associated with the metabolic syndrome (MS) and arterial calcification. Design and Method: In a random population sample (n = 542; 50.5% women; mean age, 49.8±13.1 years), we measured MS prevalence (IDF and AHA criteria), PTH and 25-OH-D3, serum and 24-h urinary calcium, MS components, carotid intima-media thickness (CIMT) and calcium intake from dairy products. We assessed associations in multivariable-adjusted analyses, using linear and logistic regressions. Results: The prevalence of MS was 21.0% (IDF criteria) and 23.6% (AHA criteria). MS prevalence, blood pressure, waist circumference, body mass index, fasting blood glucose, insulin and triglycerides, and CIMT increased (P < 0.042) across quartiles of the PTH/25-OH-D3 ratio, whereas serum and 24-h urinary calcium decreased (P < 0.029). Waist circumference and fasting blood glucose decreased across quartiles of habitual calcium intake (P < 0.04). In models that included MS (IDF) and PTH/25-OH-D3, the regression coefficients for PTH/25-OH-D3 ratio and MS were +51.3-m (P = 0.013) and +18.9-m (P = 0.45), respectively. Multivariable adjusted analyses were confirmatory. Conclusions: MS prevalence and CIMT were positively associated with PTH/25-OH-D3. CIMT was not associated with MS In the presence of PTH/25-OH-D3. Assuming causal and reversible associations, a high dietary calcium intake might protect against arterial calcification and MS.