Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study.

BACKGROUND: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION: NCT00901355, registered on ClinicalTrials.gov website.

Long-Term Angiotensin II Receptor Blockade Limits Hypertension, Aortic Dysfunction, and Structural Remodeling in a Rat Model of Chronic Kidney Disease.

BACKGROUND/AIMS: Chronic kidney disease (CKD) is associated with large artery remodeling, endothelial dysfunction and calcification, with angiotensin II (Ang II) a known driver of these pathologies. We investigated long-term Ang II type 1 receptor inhibition with valsartan on aortic function and structure in the Lewis polycystic kidney (LPK) rat model of CKD. METHODS: Mixed sex LPK and Lewis control (total n = 28) treated (valsartan 60 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups were studied. Functional responses to noradrenaline (NA), potassium chloride and endothelium-dependent and independent relaxations were investigated in vitro using acetylcholine hydrochloride (ACh) and sodium nitroprusside (SNP), respectively. Effects of the nitric oxide synthase (NOS) substrate L-arginine, NOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin on ACh responses were examined. RESULTS: In the LPK, valsartan reduced systolic blood pressure and urinary protein, ameliorated exaggerated sensitivity to NA, and normalized endothelium-dependent (ACh-Rmax; 91 ± 7 vs. 59 ± 6%, p = 0.0001) and independent dysfunction (SNP-Rmax; 99 ± 1 vs. 82 ± 7%, p = 0.040), as well as improving NO-dependent relaxation (Rmax; -51 ± 6 vs. -26 ± 9%, p = 0.008). Valsartan also reduced aortic wall hypertrophy, elastin disruption/fragmentation, calcification, media cystic degeneration, and levels of matrix metalloproteinase 9. CONCLUSIONS: This study highlights the role of Ang II in driving vascular manifestations of CKD and indicates that early treatment can significantly limit pathological changes.

Does Replacing Sodium Excreted in Sweat Attenuate the Health Benefits of Physical Activity?

International guidelines suggest limiting sodium intake to 86-100 mmol/day, but average intake exceeds 150 mmol/day. Participants in physical activities are, however, advised to increase sodium intake before, during and after exercise to ensure euhydration, replace sodium lost in sweat, speed rehydration and maintain performance. A similar range of health benefits is attributable to exercise and to reduction in sodium intake, including reductions in blood pressure (BP) and the increase of BP with age, reduced risk of stroke and other cardiovascular diseases, and reduced risk of osteoporosis and dementia. Sweat typically contains 40-60 mmol/L of sodium, leading to approximately 20-90 mmol of sodium lost in one exercise session with sweat rates of 0.5-1.5 L/h. Reductions in sodium intake of 20-90 mmol/day have been associated with substantial health benefits. Homeostatic systems reduce sweat sodium as low as 3-10 mmol/L to prevent excessive sodium loss. "Salty sweaters" may be individuals with high sodium intake who perpetuate their "salty sweat" condition by continual replacement of sodium excreted in sweat. Studies of prolonged high intensity exercise in hot environments suggest that sodium supplementation is not necessary to prevent hyponatremia during exercise lasting up to 6 hr. We examine the novel hypothesis that sodium excreted in sweat during physical activity offsets a significant fraction of excess dietary sodium, and hence may contribute part of the health benefits of exercise. Replacing sodium lost in sweat during exercise may improve physical performance, but may attenuate the long-term health benefits of exercise.

A combination of genetic, molecular and haemodynamic risk factors contributes to the formation, enlargement and rupture of brain aneurysms.

Many people carry cerebral aneurysms but are generally unaware of their presence until they rupture, resulting in high morbidity or mortality. The pathogenesis and aetiology of aneurysms are largely unknown; however, a greater understanding, by analysing the genetic, molecular and haemodynamic risk factors involved in the initiation, enlargement, and rupture of aneurysms, could lead to effective prevention, early diagnosis and more effective treatment. The risk of aneurysm is increased by a family history of aneurysms, and amongst certain populations, namely in Japan and Finland. Several other risk factors are documented, including hypertension, smoking, alcohol consumption, and female sex. Studies indicate a higher occurrence of cerebral aneurysms in females compared to males. Oestrogen protects several components within the artery wall, and inhibits some of the inflammatory molecules that could cause aneurysms. At menopause, the oestrogen level decreases and the incidence of aneurysm increases. Haemodynamic stresses have been shown to be involved in the formation, growth and rupture of aneurysms. This is often associated with hypertension, which also increases the risk of aneurysm rupture. When an unruptured aneurysm is detected the decision to treat can be complicated, since only 1-2% of aneurysms eventually rupture. Haemodynamic simulation software offers an effective tool for the consideration of treatment options for patients who carry unruptured aneurysms. The assessment must consider the risks of interventional treatments versus non-interventional management options, such as controlling blood pressure.

Central blood pressure, arterial waveform analysis, and vascular risk factors in glaucoma.

PURPOSE: Reduced ocular perfusion pressure has been linked to glaucoma, and increased arterial stiffness is implicated in systemic cardiovascular risk. This study measured central blood pressure (BP) and arterial waveforms derived from pulse tonometry, together with data on systemic and ocular vascular factors relevant to glaucoma status. METHODS: A total of 126 patients and 66 normal controls were tested, including 90 primary open-angle glaucoma (POAG) patients and 36 normal tension glaucoma (NTG) patients. Glaucoma patients had been followed for at least 3 years and inclusion required several (>4) reliable visual fields such that glaucoma progression could be determined. Radial pulse tonometry and brachial BP data were collected, together with data on disc hemorrhages, spontaneous venous pulsation, peripapillary atrophy, smoking, and medications. RESULTS: Brachial BP or derived central aortic BP parameters generally showed no significant differences between glaucoma patients and normal individuals. The POAG group had a lower pulse pressure, which was also significant in the regression analysis (P<0.002). In the arterial waveform analysis, POAG was associated with a lower brachial form factor than NTG (P<0.001) and higher subendocardial viability ratio (P<0.008). NTG was associated with a lower body mass index, and POAG with a smoking history. There was an increased incidence of disc hemorrhages and a reduced incidence of spontaneous venous pulsations in the progressing group. CONCLUSIONS: Derived central BP does not reveal significant differences from controls or in glaucoma subgroups, but a reduced pulse pressure was identified. There may be some changes in arterial pulse waveform shape suggesting possible differences in diastolic perfusion. Disc hemorrhages and loss of spontaneous venous pulsation were associated with disease progression.

Angiotensin-converting enzyme inhibitor limits pulse-wave velocity and aortic calcification in a rat model of cystic renal disease.

The effect of angiotensin-converting enzyme inhibition on function and structure of the aorta was studied in the Lewis polycystic kidney (LPK) rat model of cystic renal disease and Lewis controls. Pulse-wave velocity (PWV) was recorded under urethane anesthesia (1.3 g/kg ip) in mixed-sex animals aged 6 and 12 wk and in 12-wk-old animals treated with perindopril (3 mg·kg(-1)·day(-1) po) from age 6-12 wk. Tail-cuff systolic pressures were recorded over the treatment period. After PWV measurements, animals were euthanized and the aorta was removed for histomorphological and calcium analysis. Hypertension in LPK at 6 and 12 wk was associated with a shift of the PWV curve upward and to the right, indicating a decrease in aortic compliance, which was significantly reduced by perindopril. LPK demonstrated greater aortic calcification (6 wk: 123 ± 19 vs. 65 ± 7 and 12 wk: 406 ± 6 vs. 67 ± 6 µmol/g, P < 0.001, LPK vs. Lewis, respectively). This was reduced by treatment with perindopril (172 ± 48 µmol/g, 12 wk LPK P < 0.001). Medial cross-sectional area and elastic modulus/wall stress of the aorta were greater in LPK vs. Lewis control animals at 6 and 12 wk of age and showed an age-related increase that was prevented by treatment with perindopril (P < 0.001). Perindopril also ameliorated the degradation of elastin, increase in collagen content, and medial elastocalcinosis seen in 12-wk LPK. Overall, perindopril improved the structural and functional indices of aortic stiffness in the LPK rats, demonstrating a capacity for angiotensin-converting enzyme inhibition to limit vascular remodeling in chronic kidney disease.

Aortic stiffness is associated with vascular calcification and remodeling in a chronic kidney disease rat model.

Increased aortic pulse-wave velocity (PWV) reflects increased arterial stiffness and is a strong predictor of cardiovascular risk in chronic kidney disease (CKD). We examined functional and structural correlations among PWV, aortic calcification, and vascular remodeling in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Hemodynamic parameters and beat-to-beat aortic PWV were recorded in urethane-anesthetized animals [12-wk-old hypertensive female LPK rats (n = 5)] before the onset of end-stage renal disease and their age- and sex-matched normotensive controls (Lewis, n = 6). Animals were euthanized, and the aorta was collected to measure calcium content by atomic absorption spectrophotometry. A separate cohort of animals (n = 5/group) were anesthetized with pentobarbitone sodium and pressure perfused with formalin, and the aorta was collected for histomorphometry, which allowed calculation of aortic wall thickness, medial cross-sectional area (MCSA), elastic modulus (EM), and wall stress (WS), size and density of smooth muscle nuclei, and relative content of lamellae, interlamellae elastin, and collagen. Mean arterial pressure (MAP) and PWV were significantly greater in the LPK compared with Lewis (72 and 33%, respectively) animals. The LPK group had 6.8-fold greater aortic calcification, 38% greater aortic MCSA, 56% greater EM/WS, 13% greater aortic wall thickness, 21% smaller smooth muscle cell area, and 20% less elastin density with no difference in collagen fiber density. These findings demonstrate vascular remodeling and increased calcification with a functional increase in PWV and therefore aortic stiffness in hypertensive LPK rats.