Valvular heart disease and calcification in CKD: more common than appreciated.

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10-20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.

Aortic wave reflection in women and men.

Augmentation index (AIx), a marker of the number of aortic wave reflections (AWRs), is influenced not only by the magnitude of incident and reflected pressure waves but also by the time of return. A new triangulation method has been developed, enabling us to better quantify AWRs and to determine their sex differences, which may relate to body size or pulse pressure (PP) amplification, measured from the brachial PP-to-carotid PP (B/C) ratio. With the use of pulse wave analysis, AWRs were evaluated in 51 women and 72 men treated for hypertension and studied in relationship to age, blood pressure, and pulse wave velocity. When women were compared with men, AIx (expressed in %PP and adjusted to heart rate) was significantly higher, together with a significant decrease of the B/C ratio and an increase of the reflection magnitude and of the amplitude (but not the timing) of the backward pressure wave. The significance of the amplitude difference between men and women was enhanced after an adjustment to heart rate or pulse wave velocity but was abolished after an adjustment to body height or the B/C ratio. In the overall population, AIx and the reflection magnitude index were positively (r(2) = 0.39) and independently associated, after excluding confounding factors such as drug treatment. In conclusion, when compared with men, women treated for hypertension have increased AIx, related to the increased amplitude, and not timing, of backward pressure waves. This finding relates to sex differences in body size and mostly brachial-carotid PP amplification, a parameter highly related to the sex difference of cardiovascular risk.

Hypertension, Diabetes Type II, and Their Association: Role of Arterial Stiffness.

In patients with both hypertension and type II diabetes, the systolic blood pressure (SBP) increases linearly with age, while that of diastolic blood pressure (DBP) declines curvilinearly as early as age 45, all suggesting the development of increased arterial stiffness. Increased stiffness is an important, independent, and significant risk predictor in subjects with hypertension and diabetes. In patients with both diseases, stiffness assessed at the same mean arterial pressure (MAP) was significantly higher in diabetic patients. Arterial stiffness is related to age, heart rate (HR), and MAP, but in diabetic patients, it also related to diabetes duration and insulin treatment (IT). In the metabolic syndrome (MetSyn), diabetes also acts on the small arteries through capillary rarefaction to reduce the effective length of the arterial tree, increases the reflected pulse wave and thus the pulse pressure (PP). These studies indicate that diabetes and hypertension additively contribute to increased pulsatility and suggest that any means to reduce stiffness would be beneficial in these conditions.

Central hemodynamic modifications in diabetes mellitus.

Arterial stiffness in hypertension is markedly influenced by age, mean arterial pressure (MAP) and heart rate, whereas factors influencing this parameter in diabetes mellitus are not yet fully understood. The aim of our study was to compare central hemodynamics in diabetics (n = 126) versus non-diabetic controls (n = 203), most of whom were hypertensive, and with similar MAP. Anthropometric, laboratory and clinical measurements were collected. Hemodynamic parameters (central blood pressure, aortic pulse wave velocity [PWV], augmentation index [AIx] and pulse pressure amplification [PPA]) were measured using applanation tonometry. PWV and AIx were significantly higher in diabetics, after adjustment for age, gender, MAP, and heart rate. After further adjustment for metabolic syndrome, only the difference in PWV persisted (P < 0.0001). PPA was marginally altered though not significantly. In diabetics, PWV did not correlate with MAP, suggesting that other structural alterations, resulting from insulin resistance, may account for diabetic arterial stiffening to a greater extent than, and independently of, blood pressure. Chronic treatment with insulin was associated with increased PWV, independently of blood pressure, diabetes control and duration, or other common confounding variables. In conclusion, hypertensive diabetics had greater arterial stiffness than hypertensive controls. In diabetes, multiple factors affect arterial stiffening independently of hemodynamic status. Notably, insulin therapy (IT) is associated with more severe arterial stiffness, suggesting a consistent relationship between these parameters. It remains to be determined whether IT should be considered as a marker of diabetes severity that leads to increased arterial stiffness, or whether it has a direct/indirect effect on arterial wall modifications.

Cardiac and arterial calcifications and all-cause mortality in the elderly: the PROTEGER Study.

OBJECTIVE: To investigate the association of overall mortality with the presence and extent of cardiovascular calcifications. METHODS: We investigated the association of cardiac (mitral annulus, aortic valve) and arterial calcifications (abdominal aorta, carotid and femoral arteries) by ultrasonography, with all-cause mortality in a population of 331 high-risk elderly subjects (86.8 ± 6.9 years). After a mean follow-up of 378 days, 110 deaths occurred. RESULTS: A simple calcification score, defined by the presence of cardiac and arterial calcifications, was significantly associated with all-cause mortality (HR=1.47, 95% CI: 1.08-1.99), independent of low plasma albumin, increased plasma glucose and creatinine, as well as low diastolic blood pressure. Moreover, arterial calcifications showed negligible prognostic value with a high prevalence >89%, while cardiac calcifications significantly predicted overall mortality (HR=1.92, 95% CI: 1.28-2.87) at a prevalence of 36%. In another Cox regression, mitral annular calcification was proved to be a significant predictor of total mortality (HR=1.61, 95% CI: 1.02-2.54). CONCLUSION: The independent association between the extent of calcification and all-cause mortality is consistently significant in this frail elderly population. Arterial calcification presents a very high prevalence but a low predictive value, whereas in cardiac calcification, prevalence is lower but predictive value is much higher.

[Anthracycline-induced cardiomyopathy]. / Cardiopathie aux anthracyclines.

Anthracycline-based antineoplastic therapy is the standard of care for various cancers today and represents a breakthrough in this area. The cardiac toxicity of anthracyclines is well established. The acute form is often reversible and has no predictive value for the future. This early form does not prevent continuation of chemotherapy. Late cardiac toxicity due to anthracycline is the leading limiting factor in its use. In adults, this resembles dilated cardiomyopathy, while in children it may be expressed as restrictive cardiomyopathy. The discovery of modifiable risk factors has made it possible to identify patients at high risk of developing late cardiac toxicity and heart failure. Because left ventricular dysfunction and heart failure may develop long after anthracycline treatment ends, prolonged close follow-up is mandatory in asymptomatic subjects. Follow-up of asymptomatic patients requires serial echocardiography (M-mode, 2D echo, Doppler, tissue Doppler, speckle tracking, etc.). Anthracycline-induced cardiomyopathy must be treated according to the standard guidelines for chronic heart failure with left ventricular dysfunction, by angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Lifestyle changes may reduce the long-term risk. Close collaboration between cardiologists and oncologists is highly desirable for optimizing management of these patients.

Predictive factors for all-cause mortality in the hospitalized elderly subject: the importance of arrhythmia.

BACKGROUND: In elderly patients traditional cardiovascular (CV) risk factors are poorly correlated with mortality and few data are available on determinants and consequences of supra-ventricular arrhythmia. In a cohort of 331 hospitalized elderly patients (mean age+/-SD=85+/-7 years), we assessed which CV characteristics were associated with all-cause mortality. AIM OF THE STUDY: We wished to determine whether the presence of arrhythmia was associated with an increase of overall mortality in the hospitalized elderly population, and to ascertain which factors were associated with arrhythmia, in order to better understand the underlying mechanisms of both arrhythmia and arrhythmia-related mortality in these patients. RESULTS: The relative hazard for overall mortality in the presence of arrhythmia was 2.40 (95% CI: 1.41-4.07; p<0.001), independent of major confounding factors, compared to sinus rhythm. Both arrhythmia and low DBP were independent predictors of mortality but no association or interaction between arrhythmia and DBP was observed. The left atrium diameter was found to be a predictor of arrhythmia, and when entered in the Cox regression analysis, it suppressed arrhythmia from the model predicting all-cause mortality. CONCLUSION: In the hospitalized elderly, arrhythmia is an independent predictor of all-cause mortality, and left atrium size is an independent predictor of both arrhythmia and mortality, suggesting that links exist. Therapeutic management could therefore focus more on prevention of heart structure remodelling than on traditional risk factors.