A comparison of three different methods to determine arterial compliance in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

BACKGROUND: Several different techniques to evaluate arterial compliance have been described but have not been simultaneously tested in a large-scale, population-based setting. This study aimed to evaluate the feasibility and relation to cardiac risk of three of these techniques in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS AND RESULTS: In the population-based PIVUS study (1016 participants aged 70), assessment of arterial distensibility by ultrasound in the carotid artery, by pulse wave analysis (augmentation index) and the stroke volume to pulse pressure ratio by echocardiography were successfully employed in 86, 92, 91 and 77% of the sample, respectively. All three indices of arterial compliance were inter-related (r = 0.19-0.34, P < 0.0001 for all). Although all three indices were significantly related to the Framingham risk score (r = 0.12-0.32, P = 0.0005-0.0001), only carotid artery distensibility and the stroke volume to pulse pressure ratio were independently associated with the Framingham score in multiple regression analysis (P < 0.0001 for both). CONCLUSIONS: All three indices to evaluate arterial compliance were feasible to obtain in a general elderly population and were inter-related. Although all of the techniques were correlated to Framingham risk score, only carotid artery distensibility and the stroke volume to pulse pressure ratio were independently related to coronary risk, suggesting complementary use of these two indices of arterial compliance in the future.     

Arterial compliance influences the measurement of flow-mediated vasodilation, but not acetylcholine-mediated forearm blood flow. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

OBJECTIVES: Flow-mediated vasodilation (FMD) is low even in healthy elderly and therefore relations between FMD and cardiovascular risk factors might be hard to evaluate in the elderly. Using data from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, we investigated if a reduced arterial distensibility could influence FMD measurements. METHODS: In the population-based PIVUS study (1016 subjects aged 70), assessments of arterial distensibility by ultrasound in the carotid artery (CCA) and FMD were performed. Endothelium-dependent vasodilation was also evaluated with the invasive forearm technique with acetylcholine (EDV) and by pulse wave analysis following terbutaline injection. A poor CCA distensibility was defined as <25th percentile in the healthy part of the population (n=131). RESULTS: FMD was significantly related to the Framingham risk score only in those with a good CCA distensibility (r=-0.16, p=0.0081 versus r=-0.06, p=0.17 in those with a poor CCA distensibility, p=0.0001 for difference). In contrast, the relationship between EDV and coronary risk was not affected by CCA distensibility (r=-0.11, p=0.018 versus r=-0.13, p=0.027). CONCLUSIONS: A reduced CCA distensibility could in part explain the low FMD values in the elderly. FMD correlated to the Framingham risk score only in those with a good CCA distensibility, exemplifying a limitation of the use of FMD in elderly populations. On the contrary, EDV was not affected by arterial stiffness.     

Vasodilation in resistance arteries is related to the apolipoprotein B/A1 ratio in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

BACKGROUND: Recent studies have shown the apolipoprotein B to apolipoprotein A1 ratio (apoB/A1) to be superior to LDL-cholesterol measurements to predict cardiovascular events. The present study aims to relate apoB/A1 to endothelium-dependent vasodilation, an early marker of atherosclerosis, in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS AND RESULTS: In this population-based study, 1016 subjects aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. EDV and the pulse wave response, but not FMD, were related to apoB/A1 levels (r=-0.11, p=0.0038 for EDV, r=-0.16, p<0.0001 for the pulse wave analysis and r=0.01, p=0.65 for FMD). Neither LDL-cholesterol, nor non-HDL-cholesterol, was significantly related to the measurements of endothelium-dependent vasodilation. Also endothelium-independent vasodilation (EIDV) evaluated by the invasive forearm technique with sodium nitroprusside was related to apoB/A1 levels (r=-0.12, p<0.0016). CONCLUSION: The apoB/A1 levels, but not LDL-cholesterol, were inversely related to endothelium-dependent vasodilation evaluated by EDV and pulse wave analysis, but not by FMD. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with high apoB/A1 levels.     

Systolic and diastolic hypertension impair endothelial vasodilatory function in different types of vessels in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

BACKGROUND: Endothelium-dependent vasodilation (EDV) is known to be impaired in middle-aged hypertensive individuals, but less is known regarding hypertension in the elderly. OBJECTIVE: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to evaluate EDV in resistance and conduit arteries were applied in elderly subjects and were related to the type of hypertension. DESIGN AND METHODS: In this population-based study, 1016 subjects aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated dilatation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. Those without antihypertensive treatment were divided into three groups: normotensive individuals (n = 256), and those with isolated systolic hypertension (n = 309) or combined systolic/diastolic hypertension (n = 79). RESULTS: Compared with normotensive individuals, EDV was reduced in those with combined systolic/diastolic hypertension only (P = 0.0019), whereas FMD was mainly reduced in those with isolated systolic hypertension (P = 0.013). Furthermore, in regression analysis, EDV was related to diastolic blood pressure only (r = -0.10, P = 0.017), whereas FMD was mainly related to systolic blood pressure (r = -0.13, P = 0.0023). The pulse wave-based method to analyse vasoreactivity was not consistently affected by hypertension. CONCLUSIONS: In elderly subjects, systolic hypertension mainly impairs conduit artery endothelial vasodilatory function, whereas diastolic hypertension mainly induces dysfunction in resistance arteries.     

Left ventricular mass is related to endothelium-dependent vasodilation in the forearm, but not in the brachial artery, in elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors study

Left ventricular hypertrophy (LVH) is a powerful cardiovascular risk factor and has previously been related to endothelium-dependent vasodilation (EDV) in hypertensive patients. In the Prospective Investigation of the Vasculature in Uppsala Seniors study, different techniques to evaluate EDV in different types of vessels were applied and were related to left ventricular mass index (LVMI) in the general population. In 1016 subjects aged 70 years, EDV was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery, the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD) and the pulse wave analysis method with beta-2-agonist (terbutaline) provocation. LVMI was determined by echocardiography. LVMI was related to both EDV and the pulse wave-based technique (both r = -0.14, P < 0.0001) in univariate analysis. LVMI was also weakly related to FMD (r = -0.07, P = 0.046). However, in multiple regression analysis adjusted for gender, systolic and diastolic blood pressure and use of antihypertensive medication, only EDV was associated with LVMI (P = 0.016). EDV was mainly reduced in those with left ventricular concentric hypertrophy (P = 0.0012). In conclusion, in a population-based sample of elderly subjects, EDV, but not FMD, was inversely correlated with LVM independent of blood pressure, suggesting that EDV in resistance arteries is of more importance for LVH than endothelial vasodilatory function in conduit arteries in the elderly.     

Endothelium-dependent vasodilation in relation to different measurements of blood pressure in the elderly: the prospective investigation of the vasculature in Uppsala Seniors study

OBJECTIVES: We have earlier showed endothelium-dependent vasodilation (EDV) in forearm resistance arteries to be mainly related to diastolic blood pressure (DBP), whereas flow-mediated vasodilation (FMD) was mainly related to systolic blood pressure (SBP) when measured with a mercury sphygmomanometer in the brachial artery. Here, we investigated whether these relationships were more powerful if blood pressure was measured invasively or by transformation to central aortic blood pressure. METHODS: In the prospective study of the Vasculature in Uppsala Seniors, 1016 patients aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), and brachial artery ultrasound to assess FMD. Blood pressure was measured with a mercury sphygmomanometer, invasively in the brachial artery and transformed to aortic blood pressure by pulse wave analysis. RESULTS: EDV was related to DBP with a similar strength regardless of whether DBP was measured traditionally, invasively or as calculated aortic pressure. Similarly, FMD was related to SBP with similar strength regardless of whether SBP was measured traditionally, invasively or as calculated aortic pressure. Only FMD was significantly related to pulse pressure. CONCLUSION: Measurements of blood pressure invasively or by calculation of aortic blood pressure did not increase the power of the associations between blood pressure and EDV in the elderly, when compared with traditional blood pressure measurements.     

Endothelium-dependent flow-mediated vasodilatation,insulin resistance and the metabolic syndrome in 60-year-old men

OBJECTIVES: To evaluate the endothelium-dependent flow-mediated vasodilatation (FMD) in the brachial artery and to study the relationship to insulin sensitivity and to the metabolic syndrome in 60-year-old clinically healthy men. SUBJECTS: The men were randomly selected from the general population (n = 55). The subjects with the metabolic syndrome were defined according to a definition proposed by a working group associated with the World Health Organization (WHO). METHODS: Ultrasound images for measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery, both with and without ischaemic hand exercise during the occlusion. Insulin-mediated glucose uptake was determined by euglycaemic hyperinsulinaemic clamp as a measure of insulin sensitivity. RESULTS: The FMD was in the total group 3.2% when hyperaemia was induced by occlusion only and 8.7% after occlusion plus ischaemic hand exercise (P < 0.001, n = 51). However, no relationship was observed between any measure of FMD and insulin-mediated glucose uptake (r = -0.05 and r = 0.06, n = 47, P > 0.30). Furthermore, subjects with the metabolic syndrome (n = 13) did not differ in any measure of FMD compared with those with no risk factors (n = 11). CONCLUSION: In this study the ultrasound method to evaluate endothelial function did not show that low insulin sensitivity or the metabolic syndrome were associated with impaired FMD in otherwise clinically healthy 60-year-old men.     

老年高血压与胰岛素抵抗及代谢综合征的关系

大量的流行病学研究资料已证实 ,糖耐量降低 ,包括糖耐量受损(impairedglucosetolerance ,IGT)或明显的糖尿病常伴有高血压。此种伴发关系始终存在 ,与那些可能会影响血压水平的各种因素无关。UKPDS试验 (UnitedKingdomProspec tiveDiabetesStudy ,英国前瞻性糖尿病研究 ,1985年 )中初诊断的 2型糖尿病患者 ,几乎半数有高血压 ,而预期值约为 30 %[1～ 3 ] 。在Joslin医院资料库和UKPDS研究中高血压的发生率糖尿病患者显著高于非糖尿病患者 ,女性患者尤其如此。1　血浆胰岛素和高血压美国圣安东尼心脏研究 (SanAntonioheartstudy)中…     

Whole blood viscosity and erythrocyte deformability are related to endothelium-dependent vasodilation and coronary risk in the elderly. The prospective investigation of the vasculature in Uppsala seniors (PIVUS) study

It has previously been shown that a high hemoglobin value, a major determinant of whole blood viscosity (WBV), predicts cardiovascular events. One putative mechanism might be an impaired endothelial function. Erythrocyte deformability is another rheologic feature of the erythrocyte being of importance for the flow properties of the blood, especially in the capillaries. The present study evaluates the relationships between blood viscosity, erythrocyte deformability assessed as erythrocyte fluidity (EF), coronary risk and endothelial vasodilatory function. In the population-based PIVUS study (1016 subjects aged 70); endothelium-dependent vasodilation (EDV) was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). WBV, plasma viscosity (PV) and EF were measured in a random sample of 573 subjects. WBV and PV were positively and EF negatively related to Framingham risk score. EDV was inversely related to both whole blood and plasma viscosity. FMD was not related to any rheologic variable. In multiple regression analyses WBV and EF were significantly related to EDV independently of gender, hypertension, smoking, hypercholesterolemia, obesity and diabetes. Acetylcholine-induced vasodilation in the forearm, but not FMD, was negatively related to whole blood viscosity and positively related to EF independently of traditional risk factors in elderly subjects, indicating a pathophysiological link between impaired hemorheology and coronary risk.     

Hypertension, insulin resistance, and the metabolic syndrome.

Impaired glucose homeostasis, hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, and central obesity tend to cluster in patients to generate a syndrome, the metabolic syndrome. In the adult population, the metabolic syndrome prevalence ranges between 15% and 25%. Poor fibrinolysis and low-grade inflammation also are associated with the metabolic syndrome,and they contribute to make it a condition that predisposes to cardiovascular disease. Insulin resistance and attendant hyperinsulinemia are the characteristic features of the metabolic syndrome and probably are responsible for impairment in glucose homeostasis,dyslipidemia, and higher blood pressure through cause-and-effect relationships. While awaiting the results of clinical trials with cardiovascular endpoints, we should treat the metabolic syndrome with aggressive lifestyle intervention and consider drugs that improve the whole cardiovascular risk profile.     

Diabetes, insulin resistance, and metabolic syndrome in horses

Analogous to the situation in human medicine, contemporary practices in horse management, which incorporate lengthy periods of physical inactivity coupled with provision of nutritional rations characterized by inappropriately high sugar and starch, have led to obesity being more commonly recognized by practitioners of equine veterinary practice. In many of these cases, obesity is associated with insulin resistance (IR) and glucose intolerance. An equine metabolic syndrome (MS) has been described that is similar to the human MS in that both IR and aspects of obesity represent cornerstones of its definition. Unlike its human counterpart, identification of the equine metabolic syndrome (EMS) portends greater risk for development of laminitis, a chronic, crippling affliction of the equine hoof. When severe, laminitis sometimes necessitates euthanasia. Unlike the human condition, the risk of developing type 2 diabetes mellitus and many other chronic conditions, for which the risk is recognized as increased in the face of MS, is less likely in horses. The equine veterinary literature has been replete with reports of scientific investigations regarding the epidemiology, pathophysiology, and treatment of EMS.     

Frequency of the WHO metabolic syndrome in European cohorts,and an alternative definition of an insulin resistance syndrome

BACKGROUND: To describe the frequency, in some European populations, of the World Health Organisation (WHO) defined metabolic syndrome and to compare the frequency of this syndrome with an alternative definition for non-diabetic subjects, called the insulin resistance syndrome proposed by the European Group for the Study of Insulin Resistance (EGIR). METHODS: Investigators of eight European studies contributed, according to a written protocol, the frequencies of abnormalities of these two syndromes, by sex and age class, as well as the overall frequencies of the syndromes and the average number of abnormalities: 8200 men and 9363 women were included. RESULTS: The frequency of both syndromes increased with age and was almost always higher in men than women for a given age. In non-diabetic subjects the frequency of the WHO syndrome varied between 7% and 36% for men 40 to 55 years; for women of the same age, between 5% and 22%. The EGIR syndrome was less frequent than the WHO syndrome (1% to 22% in men, 1% to 14% in women 40-55 years), and in men this was mainly due to the differing definitions of central obesity, as the WHO definition included overall obesity, BMI > or = 30 kg/m(2). CONCLUSIONS: There is great variability in the frequency of the syndrome between different populations, due to the differing frequencies of the abnormalities and no doubt to the differing methodologies of measurement. Prospective studies and advances in the knowledge of physio-pathological mechanisms are required to determine the most appropriate and practical definition of the syndrome.     

Baroreceptor sensitivity is impaired in elderly subjects with metabolic syndrome and insulin resistance

OBJECTIVE: Metabolic syndrome consists of a collection of cardiovascular risk factors and is considered to increase the risk of cardiovascular morbidity and mortality. This study aimed to investigate whether altered baroreflex sensitivity (BRS), a measure of cardiovascular autonomic control, is related to metabolic syndrome and insulin resistance. DESIGN AND METHODS: Spontaneously occurring fluctuations in blood pressure and heart rate were recorded during 5 min of controlled breathing in a population sample of 1016 subjects aged 70 (the Prospective Investigation of the Vasculature in Uppsala Seniors study). BRS was calculated through both sequence and frequency domain analysis in 77% of the sample. RESULTS: BRS was reduced in those with metabolic syndrome (n = 172, median 4.3 versus 5.7; P < 0.0001 after correction for heart rate, cardiovascular diagnosis and medication) and was reduced in proportion to the number of fulfilled National Cholesterol Education Program/Adult Treatment Panel III metabolic syndrome criteria (P < 0.0001). BRS was inversely related to insulin resistance, calculated by homeostatic model assessment (HOMA index; r = -0.18, P < 0.0001). CONCLUSIONS: Cardiovascular autonomic imbalance, measured as a reduced BRS, is present in metabolic syndrome and in subjects with insulin resistance. As BRS mainly reflects vagal activity, future prospective studies will address the possibility of vagal impairment in the pathogenesis of metabolic syndrome.     

Obstructive sleep apnea and the metabolic syndrome in an elderly healthy population: the SYNAPSE cohort

Background

Obstructive sleep apnea syndrome (OSA) has been recently considered as a cause and a component of the metabolic syndrome (MetS), previous studies showing the presence of OSA in about half of middle-aged patients having MetS. To date, no study has considered the association of OSA and MetS in the elderly. In this study we examine the prevalence of MetS and its strength association among healthy elderly OSA subjects.

Methods

A cohort of 806 subjects aged 68.5?years, participants of a 7-year follow-up study, was examined. All subjects underwent clinical evaluation, blood sample measurements, and an at-home polygraphy. OSA was assessed as an apnea/hypopnea index (AHI) >15, and MetS was diagnosed according to the Adult Treatment Panel III.

Results

In the total group, 9.8% of cases met criteria for MetS with a prevalence similar in men and women. Of the entire group with Mets, 51.3% were women and 48.7% men. OSA was diagnosed in 55.9% of the sample, and among the OSA group, 12.5% had MetS. Oxyhemoglobin desaturation index (ODI, p?p?=?0.003) were found significantly higher in subjects with MetS than in those without it. Most of MetS components were significantly associated with AHI and ODI, the relationship stronger with ODI. After adjustment for covariables such as obesity, gender, and presence of diabetes, ODI was independently associated with three MetS components, glycemia (p?p?=?0.002), and triglyceride levels (p?=?0.02). Sleepiness, autonomic arousal index, and sleep duration had no effect on the metabolic parameters.

Conclusions

In elderly subjects, the association between OSA and MetS was stronger for hyperglycemia and hypertension. Among factors explaining this association, hypoxemia appears to be the most important factor without any effect of indices of sleep fragmentation, sleep duration, and sleepiness.     

Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association

This study aims to determine the presence of the components of the metabolic syndrome in primary nonalcoholic steatohepatitis (NASH) and to assess the role of liver disease in the genesis of peripheral hyperinsulinemia. Nineteen patients (18 men and 1 woman; mean age, +/- SD, 38 +/- 10 years; body mass index [BMI], 26 +/- 2 kg/m(2)) with histologic evidence of NASH were enrolled; 19 age- and sex-matched normal subjects were investigated as controls. Plasma glucose, insulin, and C-peptide levels were measured during an oral glucose tolerance test, and a frequently sampled intravenous glucose tolerance test (FSIGT), analyzed by minimal modeling technique, was performed. Compared with controls, the NASH group had lower insulin sensitivity (3.84 +/- 2.44 vs. 7.48 +/- 3.01 10(-4) x min(-1)/microU/mL; P =.0003) and higher total insulin secretion (21 +/- 13 vs. 10 +/- 3 nmol/L in 240 minutes; P =.001). Hepatic insulin extraction was similar in both groups (69.8% +/- 16.1% vs. 70.2% +/- 18.3%; P =.854). According to the results of the oral glucose tolerance test, no patient was classified as diabetic, 5 were classified as glucose intolerant, and 1 was classified as having impaired fasting glycemia. Nine patients (47%) had at least the 2 minimum criteria required to define the metabolic syndrome according to the European Group for the Study of Insulin Resistance (EGIR). In conclusion, hyperinsulinemia and insulin resistance occur frequently in patients with NASH; these conditions do not stem from a reduced hepatic insulin extraction but from an enhanced pancreatic insulin secretion compensatory to reduced insulin sensitivity. The derangement of insulin regulation, often associated with the metabolic syndrome, may play a causal role in the pathogenesis of NASH.     

Lipoprotein particle distribution and size, insulin resistance, and metabolic syndrome in Alaska Eskimos: the GOCADAN study

Background

Metabolic syndrome (MS) is associated with dyslipidemia, and insulin resistance (IR) may be a main determinant of this dyslipidemia.

Objective

To determine how lipoprotein particle concentration and size are related to MS and IR in a population-based sample of Alaska Eskimos.

Design

Participants underwent a physical exam, personal interview, collection of biological specimens, and diagnostic tests.

Setting

This study was conducted in the Norton Sound region of Alaska.

Participants

One thousand one hundred fifty-eight Inupiat Eskimo adults (women = 653, men = 505).

Main outcome measures

Lipoprotein particle profile was evaluated by nuclear magnetic resonance (NMR) and related to presence of MS and level of IR.

Results

Participants with MS had (a) significantly higher concentrations of all VLDLs and a larger VLDL size (women, p = 0.007; men, p = 0.0001); (b) higher concentrations of small LDL (women, p < 0.0001; men, p = 0.09) and lower concentrations of large LDL (women, p < 0.0001), leading to a smaller overall LDL size (women, p < 0.0001; men, p < 0.05); (c) significantly lower concentrations of large HDL (both genders, p < 0.0001) and an increase in intermediate (women, p < 0.05) and small HDL (women, p < 0.0001; men, p < 0.004). Lipoprotein profile with increasing HOMA-IR resembled that of individuals with MS.

Conclusions

In this population MS is characterized by lipoprotein distribution and size abnormalities independent of obesity, age, and other cardiovascular risk factors, including lipid concentration. IR seems the major determinant.