Louise Shiel

Age-Related Deterioration in Arterial Structure and Function in Postmenopausal Women: Impact of Hormone Replacement Therapy

Epidemiological evidence suggests that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular diseases in postmenopausal women. In this study, indices of arterial function [total systemic arterial compliance (SAC) and carotid arterial distensibility coefficient (DC)], structure [carotid intima-media thickness (IMT)], and lipid profiles were compared in postmenopausal women on long-term HRT and aged-matched controls. One hundred nine women aged 44 to 77 years taking HRT and an age-matched group of 108 female controls were entered into the study. The two groups were similar for body mass index, smoking status, exercise level, alcohol intake, and blood pressure. Fasting cholesterol, low density lipoprotein, and lipoprotein(a) were reduced and high density lipoprotein increased in the HRT group. IMT increased with age; SAC and DC were reduced with age in both groups. The HRT group had a higher mean SAC (0.42+/-0.02 versus 0.34+/-0.02 U/mm Hg, P=0.0001) and a lower mean IMT (0.67+/-0.01 versus 0.74+/-0.02 mm, P=0.006) than did controls. Subgroup analysis for estrogen versus estrogen plus progestin revealed no differences for SAC and IMT; DC, however, was greater in estrogen-only users. Smokers on HRT had a higher mean SAC (0.41+/-0.02 versus 0.31+/-0.01 U/mm Hg, P=0.008) and a lower IMT (0.65+/-0.02 versus 0.75+/-0.03 mm, P=0.002) than did smokers not taking such therapy. A protective effect of long-term estrogen therapy on age-related changes in arterial structure and function in postmenopausal women was evident in smokers and nonsmokers alike. Progestin appeared to counteract the effects of estrogen on carotid compliance only. Long-term controlled trials are needed to determine the significance of these findings.

Effects of Blood Pressure, Smoking, and Their Interaction on Carotid Artery Structure and Function

In the present study, we examined the relationships among carotid blood pressure, arterial geometry, and wall stress and determined the impact of hypertension, smoking status, and their interaction on these relationships. The study involved 679 subjects aged 49 to 82 years: 372 smokers (190 men and 182 women) and 307 nonsmokers (110 men and 197 women). Blood samples were taken to determine total cholesterol levels. Central pulse pressure was derived from measured brachial artery pressure with a linear regression equation from data obtained in a subgroup of 276 subjects that related brachial and carotid pulse pressures; the latter was measured with applanation tonometry. Carotid intima-media thickness (IMT), lumen diameter (D), and stiffness index (SI) were determined with high-resolution B-mode ultrasound. Mean and pulsatile circumferential stress (&sfgr;C) was calculated according to the Laplace relationship. Indexes of arterial geometry and function were adjusted for age, height, and heart rate. Hypertension (treated and/or screening blood pressure of >140/90 mm Hg) was present in 71 nonsmokers and 186 smokers. Nonsmokers and smokers did not differ in blood pressure and cholesterol levels. Hypertension and smoking individually and interactively significantly increased adjusted IMT, D, and SI. The radius-to–wall thickness ratio (R/IMT) (where R=D/2) and &sfgr;C were increased in hypertensives. SI was correlated with IMT (r =0.56, P <0.001); radius-to–wall thickness ratio was inversely correlated with central pulse pressure (r =−0.38, P <0.001). Smoking did not influence these relationships. In conclusion, carotid artery wall remodeling appears to follow Laplace’s law but is insufficient to prevent an increase in circumferential stress in hypertensive subjects. Unlike hypertension, smoking does not influence the lumen-to-wall ratio but has a significant effect on wall stiffness.

A pragmatic randomized trial of a polypill-based strategy to improve use of indicated preventive treatments in people at high cardiovascular disease risk

Background Most individuals at high cardiovascular disease (CVD) risk worldwide do not receive any or optimal preventive drugs. We aimed to determine whether fixed dose combinations of generic drugs (‘polypills’) would promote use of such medications. Methods We conducted a randomized, open-label trial involving 623 participants from Australian general practices. Participants had established CVD or an estimated five-year CVD risk of ≥15%, with indications for antiplatelet, statin and ≥2 blood pressure lowering drugs (‘combination treatment’). Participants randomized to the ‘polypill-based strategy’ received a polypill containing aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg. Participants randomized to ‘usual care’ continued with separate medications and doses as prescribed by their doctor. Primary outcomes were self-reported combination treatment use, systolic blood pressure and total cholesterol. Results After a median of 18 months, the polypill-based strategy was associated with greater use of combination treatment (70% vs. 47%; relative risk 1.49, (95% confidence interval (CI) 1.30 to 1.72) p < 0.0001; number needed to treat = 4.4 (3.3 to 6.6)) without differences in systolic blood pressure (−1.5 mmHg (95% CI −4.0 to 1.0) p = 0.24) or total cholesterol (0.08 mmol/l (95% CI −0.06 to 0.22) p = 0.26). At study end, 17% and 67% of participants in polypill and usual care groups, respectively, were taking atorvastatin or rosuvastatin. Conclusion Provision of a polypill improved self-reported use of indicated preventive treatments. The lack of differences in blood pressure and cholesterol may reflect limited study power, although for cholesterol, improved statin use in the polypill group counter-balanced use of more potent statins with usual care.

EFFECTS OF OESTROGEN AND PROGESTERONE ON AGE-RELATED CHANGES IN ARTERIES OF POSTMENOPAUSAL WOMEN

1. Hormone replacement therapy (HRT) with oestrogen or oestrogen plus progestin may have different effects on arterial structure and function. To examine this question, carotid artery intima‐medial thickness (IMT) and indices of systemic and carotid arterial compliance were measured in groups of older men, postmenopausal women not on HRT (non‐HRT) and those women on long‐term HRT with oestrogen alone (HRT‐E) or oestrogen plus progestin (HRT‐EP).

Carotid artery intima-medial thickness is increased in chronic renal failure.

1. Chronic renal failure (CRF) is associated with rapidly progressive atherosclerotic vascular disease. In the present study, carotid arterial intima–medial thickness (IMT) was assessed in a large cohort of patients with CRF and matched controls and related to risk factors.

Hormone replacement therapy in postmenopausal women protects against smoking-induced changes in vascular structure and function

OBJECTIVES The purpose of this study was to investigate the role of hormone replacement therapy (HRT) in postmenopausal women who smoke. BACKGROUND Hormone replacement therapy appears to afford cardiovascular protection in postmenopausal women; however, in high risk individuals, specifically smokers, this has not been adequately studied. This question was addressed in a cross-sectional study of arterial structure, function and plasma lipids in postmenopausal smokers and nonsmokers. METHODS Vascular ultrasound was performed in two age-matched groups of postmenopausal women, 70 on HRT (35 smokers) and 70 control subjects not on HRT (35 smokers). Indexes of arterial structure (carotid intima-media thickness [IMT]) and vascular function (systemic arterial compliance [SAC]) and lipid profiles were measured. RESULTS Participant characteristics were similar in the two groups. Smokers on HRT, compared with smoking control subjects, had lower cholesterol (6.0+/-0.2 vs. 6.8+/-0.3 mmol/liter, p = 0.03) and more favorable mean values for IMT (0.64+/-0.02 vs. 0.74+/-0.03 mm, p = 0.007) and SAC (0.41+/-0.03 vs. 0.32+/-0.03 U/mm Hg, p = 0.03). Nonsmokers on HRT compared with nonsmoking control subjects had lower total cholesterol (5.7+/-0.2 vs. 6.5+/-0.2 mmol/liter, p = 0.02) and low density lipoprotein cholesterol (3.4+/-0.2 vs. 4.4+/-0.3 mmol/liter, p = 0.01). Mean IMT and SAC values in nonsmokers on HRT and control subjects were not significantly different. Multiple regression demonstrated significant correlation between HRT status and both IMT and SAC, in smokers and in those with increased cholesterol. In nonsmokers and those with lower cholesterol, HRT status was not significantly correlated with vascular parameters. CONCLUSIONS In postmenopausal women who smoke there may be a beneficial effect of long-term estrogen therapy on indexes of arterial structure and function as surrogate markers of cardiovascular disease. Long-term controlled studies are needed to confirm these findings.

The Melbourne Atherosclerosis Vitamin E Trial (MAVET): A study of high dose vitamin E in smokers

Objective Our aim was to evaluate whether vitamin E (500IU) slowed the progression of carotid atherosclerosis in a population of chronic smokers over 4 years as measured by ultrasound determination of carotid intima-media thickness (IMT) and systemic arterial compliance (SAC). Methods The Melbourne Atherosclerosis Vitamin E Trial (MAVET) was a randomized, double-blind, placebo-controlled trial in which 409 male and female smokers aged 55 years and over were randomized to receive 500IU per day of natural vitamin E or placebo. The primary endpoint was progression of carotid atherosclerosis determined by intima-media thickness of the right common carotid artery. Secondary outcomes were change in systemic arterial compliance and low-density lipoprotein (LDL) oxidative susceptibility over time. Results The mean increase in intima-media thickness over time in the vitamin E group was 0.0041 mm/year faster than placebo (95% confidence interval −0.0021 to 0.0102 mm/year, P=0.20). Similarly, a non-significant difference between vitamin E and placebo was found for rate of change in systemic arterial compliance (P=0.11). Vitamin E supplementation did, however, significantly reduce LDL oxidative susceptibility (P>0.001). Conclusion Vitamin E supplementation is ineffective in reducing the progression of carotid atherosclerosis as measured by intima-media thickness in chronic smokers. This finding extends our knowledge of lack of effectiveness of vitamin E supplementation in populations with high oxidant stress. Eur J Cardiovasc Prev Rehabil 13:341-347

Ankle-Brachial Index determination and peripheral arterial disease diagnosis by an oscillometric blood pressure device in primary care: validation and diagnostic accuracy study

Objectives To determine the level of agreement between a ‘conventional’ Ankle-Brachial Index (ABI) measurement (using Doppler and mercury sphygmomanometer taken by a research nurse) and a ‘pragmatic’ ABI measure (using an oscillometric device taken by a practice nurse) in primary care. To ascertain the utility of a pragmatic ABI measure for the diagnosis of peripheral arterial disease (PAD) in primary care. Design Cross-sectional validation and diagnostic accuracy study. Descriptive analyses were used to investigate the agreement between the two procedures using the Bland and Altman method to determine whether the correlation between ABI readings varied systematically. Diagnostic accuracy was assessed via sensitivity, specificity, accuracy, likelihood ratios, positive and negative predictive values, with ABI readings dichotomised and Receiver Operating Curve analysis using both univariable and multivariable logistic regression. Setting Primary care in metropolitan and rural Victoria, Australia between October 2009 and November 2010. Participants 250 persons with cardiovascular disease (CVD) or at high risk (three or more risk factors) of CVD. Results Despite a strong association between the two methods measurements of ABI there was poor agreement with 95% of readings within ±0.4 of the 0.9 ABI cut point. The multivariable C statistic of diagnosis of PAD was 0.89. Other diagnostic measures were sensitivity 62%, specificity 92%, positive predictive value 67%, negative predictive value 90%, accuracy 85%, positive likelihood ratio 7.3 and the negative likelihood ratio 0.42. Conclusions Oscillometric ABI measures by primary care nurses on a population with a 22% prevalence of PAD lacked sufficient agreement with conventional measures to be recommended for routine diagnosis of PAD. This pragmatic method may however be used as a screening tool high-risk and overt CVD patients in primary care as it can reliably exclude the condition.

Power spectral analysis of heart-rate variability reflects the level of cardiac autonomic activity in rabbits

Power spectral analysis of heart rate (HR) variability was tested in conscious rabbits to assess the reliability of this method for assessing cardiac autonomic function in normal rabbits under resting conditions. Evaluation of power spectrum was performed in 5 rabbits under normal resting conditions and after sympathetic, parasympathetic and combined sympathetic plus parasympathetic blockade. Rabbits were randomly assigned to undergo sympathetic (propranolol) or parasympathetic (methscopolamine) blockade at the initial step followed by combined blockade. The power spectrum of heart-rate variability in rabbits was presented as one broad spectral component at frequencies mainly between 0 and 0.5 Hz. This component was considerably modulated by both sympathetic and parasympathetic influences with substantial overlap of sympathetic- and parasympathetic-related components of the spectrogram. Nevertheless, it was clearly shown that power of heart-rate variability at frequencies from 0.4373 Hz to 0.5625 Hz was determined only by parasympathetic influences, and sympathetic modulation of HR was presented mainly at frequencies from 0.0625 Hz to 0.1875 Hz. Spectral subcomponent analysis of the power spectrum of HR variability may be useful to follow changes in cardiac autonomic function in rabbits.

Most individuals with treated blood pressures above target receive only one or two antihypertensive drug classes

A significant proportion of individuals taking antihypertensive therapies fail to achieve blood pressures <140/90 mmHg. In order to develop strategies for improved treatment of blood pressure, we examined the association of blood pressure control with antihypertensive therapies and clinical and lifestyle factors in a cohort of adults at increased cardiovascular risk.