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.

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 alpha-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 alpha-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 microm, 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 alpha-adducin 460Trp or the aldosterone synthase -344T allele. These findings may have clinical implications for the assessment of genetic cardiovascular risk.

The metabolic syndrome and carotid intima-media thickness in relation to the parathyroid hormone to 25-OH-D(3) ratio in a general population.

BACKGROUND: 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. METHODS: In a random population sample (n = 542; 50.5% women; mean age, 49.8 ± 13.1 years), we measured MS prevalence (International Diabetes Federation (IDF) and American Heart Association (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 relating CIMT to PTH/25-OH-D3 ratio and MS were +51 µm (P = 0.013) and +19 µm (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. Prospective studies and intervention trials should address the causality of these associations.

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)x10(-3); 4 mg: from 13.2+/-5.2 to 12.7+/-5.9 kPa(-1)x10(-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.