Cardiometabolic determinants of mortality in a geriatric population: is there a "reverse metabolic syndrome"?

AIMS: Diabetes or insulin resistance, overweight, arterial hypertension, and dyslipidaemia are recognized risk factors for cardiovascular (CV) disease. However, their predictive value and hierarchy in elderly subjects remain uncertain. METHODS: We investigated the impact of cardiometabolic risk factors on mortality in a prospective cohort study of 331 elderly high-risk subjects (mean age+/-SD: 85+/-7 years). RESULTS: Two-year total mortality was predicted by age, diabetes, low BMI, low diastolic blood pressure (DBP), low total and HDL cholesterol, and previous CV events. The effect of diabetes was explained by previous CV events. In non-diabetic subjects, mortality was predicted by high insulin sensitivity, determined by HOMA-IR and QUICKI indices. In multivariate analyses, the strongest mortality predictors were low BMI, low HDL cholesterol and previous myocardial infarction. Albumin, a marker of malnutrition, was associated with blood pressure, total and HDL cholesterol, and HOMA-IR. The inflammation marker CRP was associated with low total and HDL cholesterol, and high HOMA-IR. CONCLUSION: In very old patients, low BMI, low DBP, low total and HDL cholesterol, and high insulin sensitivity predict total mortality, indicating a "reverse metabolic syndrome" that is probably attributable to malnutrition and/or chronic disorders. These inverse associations limit the relevance of conventional risk factors. Previous CV events and HDL cholesterol remain strong predictors of mortality. Future studies should determine if and when the prevention and treatment of malnutrition in the elderly should be incorporated into conventional CV prevention.

[Unusual cause of Takotsubo cardiomyopathy after pacemaker implantation]. / Un cas inhabituel de cardiomyopathie de Takotsubo après implantation de pacemaker.

Since its first description in Japan in 1990, Takotsubo (stress) cardiomyopathy has gained worldwide recognition. The disease is characterized by transient systolic and diastolic left ventricular dysfunction with a variety of wall-motion abnormalities. She predominantly affects elderly women and she is often preceded by an emotional or physical trigger. In the acute phase, the clinical presentation, electrocardiographic findings and biomarker profiles are often similar to those of an acute coronary syndrome. Although, the cause of Takotsubo cardiomyopathy remains unknown, the role of the brain-heart axis in the pathogenesis of the disease has been described. The potential role of catecholamine excess in the pathogenesis of Takotsubo cardiomyopathy has been long debated, and as such beta-blockers have been proposed as a therapeutic strategy. Currently, the treatment is not codified and it adapts according to clinical symptomatology. It seems difficult to summarize all the factors to provoque the cardiomyopathy, we describe a case of Takotsubo after a pacemaker (PM) implantation and to give a recent progress on this heart disease.

[Unusual cause of acute coronary syndrome: Horton's disease]. / Un syndrome coronaire aigu particulier : maladie de Horton.

The pathophysiology of acute coronary syndromes is in most cases due to the erosion or rupture of a plaque with consequent thrombotic obstruction of coronary artery. In a few cases, the mechanism is different, this not modifying the initial management but imposing special techniques for diagnosis and therapeutic management. We report a clinical case of a patient supported for an acute coronary syndrome, in a context of impaired general condition and biological inflammatory syndrome revealing a Horton's disease.

[Coronary artery fistulas, a current problem: Clinical and therapeutic considerations]. / Les fistules coronaires, un problème d'actualité : approche clinique et considérations thérapeutiques.

The coronary fistula is a link between one or more of the coronary arteries and cardiac cavity or great vessel. The exact occurrence is unknown. The majority of these fistulas are congenital in origin. However, they may occasionally be detected after cardiac surgery. For a long time, fistulas are asymptomatic, especially if they are small; the frequency of the symptoms and especially the complications rise with age. The potential complications are: cardiac failure, endocarditis, endarteritis, atrial fibrillation, ventricular arrhythmias, rupture, and thrombosis. The main differential diagnosis is patent arterial duct, while other congenital arteriovenous shunts need to be excluded. Even though echocardiography Doppler can help to differentiate shunts, the coronary angiography remains the main diagnostic tool for the description of the anatomy. For a long time, the surgery was the only therapeutic means, up till now, percutaneous occlusion is the first line therapy of coronary fistulas and that the different devices can be tailored to meet different anatomic and functional characteristics.

[Evaluation of the individual absolute cardiovascular risk. A mathematical equation and/or arterial measurement?]. / Evaluation du risque cardiovasculaire absolu individuel. Equation mathématique et (ou) mesure artérielle?

The latest recommendations about the management of cardiovascular risk factors take into account not only the level of risk factor but also the global risk profile of the patient. The reference for the calculated estimation of absolute cardiovascular risk remains the Framingham equation. Nevertheless, this estimation has a number of operational and conceptual limitations such as geographical and historical validity and its application to individual cases. Different results in the medical literature suggest that parameters of arterial structure or function measured simply, such as arterial rigidity, could be closely related to the level of individual cardiovascular risk by the integration of the deleterious effects of different vascular risk factors over decades of exposition. They could then be better predict cardiovascular effects than the result of a mathematical equation which only integrates some of the risk factors at a given point in time. These simple, rapid and non-invasive measurements could help identify subjects at high cardiovascular risk and also help the clinician in the orientation of preventive measures in subjects with cardiovascular risk factors.

[A new cause of resistant arterial hypertension: coprescription with anticonvulsant treatments]. / Une nouvelle cause d'hypertension artérielle résistante: la coprescription avec des traitements anticomitiaux.

UNLABELLED: This article provides two case reports about pharmacokinetic interactions with hypertensive drug therapy and anticonvulsive treatment. First, a 49-year-old patient presenting severe hypertension had a non-traumatic cerebral hemorrhage with convulsions. Extensive etiologic investigations did not find any cause of secondary hypertension. Under an association of four antihypertensive drugs regimen, associated with carbamazepine blood pressure was not controlled. Finally, blood pressure was well controlled after replacement of carbamazepine with vigabatrin. The second case reports a 64-year-old treatment-resistant essential hypertensive patient, carbamazepine was associated with antihypertensive treatment because of aggressivity attributed to Alzheimer's disease. After withdrawal of carbamazepine treatment, blood pressure reached normal values with the same antihypertensive regimen. Those case reports suggest drug-drug interactions between antihypertensive and anticonvulsive drug therapies. Following explanation can be hypothesis: several antihypertensive drugs are liver-metabolised by microsomal cytochrome P450 3A4 isoform that could explain a significantly decreased half-life in association with enzymatic inducers, such as rifampicine or antiepileptic drugs (phenobarbital, phenytoin or carbamazepine). CONCLUSION: When blood pressure is not controlled without cause of secondary hypertension, physicians must be careful with drug-drug interactions.

[Blood pressure self-monitoring contributes to improved patient education among hypertensive subjects]. / La possession d'un appareil d'automesure tensionnelle contribue à améliorer l'éducation des patients hypertendus.

UNLABELLED: Education of hypertensive subject must sensitize the patient to its pathway and to the prescribed treatment. Self-measurement of blood pressure, which directly implicates the patient, should ameliorate the education of hypertensive subject. OBJECTIVES: To evaluate if the possession of a self-measurement blood pressure device improves patients' knowledge of hypertension. METHODS: In 484 treated hypertensive subjects referred to hypertension specialists, a questionnaire evaluating patients knowledge of hypertension and its treatment was given before the consultation. During this consultation, the practitioner evaluated the concordance between antihypertensive treatments declared by the patient and those effectively prescribed. RESULTS: In this population, aged 61 +/- 12 years, with 55% of men, a self-measurement blood pressure device was possessed by 165 subjects (34%). These devices have been bought without medical advice by 83 patients. For a minority of subjects (n = 41), self-measurements of blood pressure were made at the wrist. Blood pressure level was similar in subjects with (141 +/- 19/80 +/- 10 mmHg) or without (140 +/- 19/80 +/- 10 mmHg) self-measurement devices. Subjects possessing a self measurement device had a better knowledge of their usual blood pressure level and of the normal blood pressure values (< 140/90 mmHg), than subjects without self measurement device (93% vs 77%, p < 0.01, and 56% vs 33%, p < 0.01, respectively). Moreover, subjects in possession of self-measurement devices had a better knowledge of their antihypertensive treatment than those without device (83% vs 70%, p < 0.05). Logistic regression analysis including age, sex, smoking, education level, blood pressure level and the number of antihypertensive tablets confirm the statistical differences observed. CONCLUSION: Hypertensive subjects who possess a self-measurement blood pressure device have a better knowledge of their hypertension. These results indicate that the possession of a self-measurement device contributes to the education of hypertensive patients.

[Rational choice for second antihypertensive agent after failure of the first monotherapy: therapeutic strategy]. / Choix raisonné du deuxième antihypertenseur après l'échec d'une première monothérapie: la stratégie des paniers thérapeutiques.

This study evaluated a strategy to treat naive hypertensive patients, based on a single monotherapy followed, in uncontrolled patients, by a rationale choice for the second antihypertensive treatment. Subjects with essential hypertension, entered into the study if their BP measured with an OMRON 705CP was > 140/90 mmHg on two separate visits. Patients were allocated to single treatment in a balanced randomized design to receive either a "group 1" treatment (ACE inhibitor, beta-blocking drug or ARB) or a "group 2" treatment (calcium channel-blocking drug or thiazide diuretic). After one month of treatment at a standard dose, if BP was > 140/90 mmHg, first adaptation was a fixed combination therapy with one drug from "group 1" and one drug from "group 2". At 3 months, patients with BP < 140/90 mmHg were considered to have reached BP goal. Forty-eight patients entered the study with a mean age of 53 +/- 11 years. Initial SBP/DBP (mmHg) was 164 +/- 16/97 +/- 8. After 1 month, 40% achieved the target BP, 52% were uncontrolled with no side effects and 8% were uncontrolled and had side effects. After 3 months, 84% achieved BP goal and a fixed combination therapy was prescribed in 52% of the controlled patients. The initial monotherapy was maintained alone or in combination in 70% of the controlled patients. A strategy based on a single monotherapy followed, if necessary, by a rational choice for the second treatment in a fixed combination therapy is effective to achieve BP control in 84% of naive hypertensive patients.

[Structure and function of the arteries of very elderly people. The PROTEGER Study (Cardiovascular Prognosis and Therapeutic Optimization in Geriatrics)]. / Structure et fonction des artères des sujets très âgés-l'étude PROTEGER. (PRonostic cardio-vasculaire et Optimisation Thérapeutique En GERiatrie).

The purpose of PROTEGER, a multicenter prospective observational study, was to determine the contribution of hemodynamic, arterial, echocardiographic and biological parameters to the evaluation of individual cardiovascular risk in the elderly. The study included patients aged over 70 years hospitalized in geriatric units with overt cardiovascular disease. Cross sectional analysis of the first 194 subjects included in the study demonstrated a high rate of arterial alterations involving both structure and function. The principal alterations observed were: high pulse pressure despite normal mean systolic and diastolic pressures, frequent and diffuse arterial calcifications, reduced compliance and distensibility, increased thickness, diameter and incremental elastic modulus of the carotid and increased pulse wave velocity. Analysis of monitoring results in the PROTEGER study will demonstrate the role of hemodynamic measurements and arterial alterations in the prediction of cardiovascular risk in hospitalized elderly.

[Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk of ventricular arrhythmia]. / Antipsychotiques et sécurité cardio-vasculaire: données actuelles sur les allongements de l'intervalle QT et le risque d'arythmies ventriculaires.

Cardiovascular mortality is higher among schizophrenic patients than in the general population, and it is possible that most unexplained sudden deaths among these patients are due to ventricular arrhythmias for which antipsychotic drugs are either the cause or a predisposing factor. Most antipsychotic agents show electrophysiological effects resembling those of class 1a antiarrhythmic agents, and may be responsible for prolonging the QT interval, potentially going on to cause torsades de pointes. Some of the antipsychotic agents carry a high risk of arrhythmias, related to their effects on the QT interval. These include thioridazine, pimozide, sultopride, droperidol, and to a lesser extent haloperidol and chlorpromazine. In the case of the new atypical antipsychotic agents, it is possible to rank the risks of different drugs, with sertindole (now withdrawn from sale) having the highest risk, and ziprasidone somewhat lower, followed by risperidone and finally by quetiapine, clozapine and olanzapine which have negligible effects on the QT interval. A number of risk factors have been demonstrated, particularly: hypokalaemia and hypomagnesaemia, bradycardia, congenital long QT syndrome, and any underlying cardiac pathology. Lastly, the risk associated with any given antipsychotic agent is increased if it is combined either with any other drug known to prolong the QT interval and provoke torsades de pointes, or with any drug capable of inhibiting the hepatic metabolism of the antipsychotic agent. A list of such drugs is provided, together with advice on the action to be taken when prescribing an antipsychotic agent to a patient with a long QT interval.

[Measurement of the carotid intima-media thickness. An innovative technique for assessing cardiovascular risk]. / La mesure de l'épaisseur intima-média carotidienne. Une technique innovante d'appréciation du risque cardio-vasculaire.

ASSESSMENT OF CARDIOVASCULAR RISK: Measurement of the intima-media thickness in the carotid artery is optimized by coupling high-resolution ultrasonography with automatic data processing systems, allowing improved precision. Although the optimal site of measurement remains controversial (common carotid, bifurcation, internal carotid), there appears to be a consensus on need for bilateral automatic measurement. The intima-media thickness is considered a marker of atheromatous disease and its diffusion. This parameter probably integrates the deleterious effect of different cardiovascular risk factors accumulated over decades. In addition, several prospective observation studies have reported a positive relationship between measurement of the intima-media thickness of the carotid artery and risk of cardiovascular events (myocardial infarction and stroke). DETECTION AID: Although the results issuing from epidemiology observation studies are still too preliminary, to evaluate the positive and negative predictive value for occurrence of clinical events in relation to different levels of thickness, this simple rapid and noninvasive measurement could be a useful tool for subjects with high cardiovascular risk. PERSPECTIVES: Measurement of arterial parameters, determined by high-resolution ultrasonography, will probably shortly become an integral part of the evaluation strategies for cardiovascular risk. Future comparative studies will provide an assessment of the comparative predictive value of these different parameters (quantitative structural analysis versus quantitative and qualitative analysis of the structure versus structural and functional analysis of the arteries).

Aortic stiffness, inflammation, denutrition and prognosis in the oldest people.

Observational studies have shown that some of the classic CV risk factors, namely hypertension or hypercholesterolemia, become nebulous, or even act in the reverse direction, in the oldest people. We investigated whether in the elderly, increased aortic stiffness was associated with higher mortality risk, before and after adjustments on common geriatric confounders. In a cohort of 331 (86 men) subjects aged >70 years (mean age (± s.d.): 85 ± 7 years), aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Classical CV risk factors were determined simultaneously, in association with inflammation and denutrition parameters. One hundred and ten subjects died during a 2-year follow-up period. In crude analysis, a positive non-significant trend was observed between PWV and mortality risk. Multivariate Cox regression analysis showed that five parameters entered the prediction model: two were positively related to mortality risk, PWV (P = 0.008) and orosomucoide (P = 0.045), and three were related negatively, total cholesterol (P = 0.006), albumin (P = 0.026) and body weight (P = 0.035). Interaction analysis revealed that the effect of PWV on mortality was increased in the presence of renal dysfunction and increased inflammation. In conclusion, although marginally significant in crude analysis, PWV is a powerful determinant of prognosis in the oldest people taking into account inflammation and denutrition.

Aortic stiffness, inflammation, denutrition and type 2 diabetes in the elderly.

AIM: Observational studies in the elderly have shown that some of the classical cardiovascular (CV) risk factors are difficult to interpret. Thus, our study investigated whether increased aortic stiffness is associated with higher mortality risk in both the diabetic and non-diabetic elderly before and after adjusting for geriatric confounders such as inflammation (sedimentation rate, C-reactive protein, orosomucoid levels, leukocyte count) and denutrition parameters (body weight, body mass index [BMI], plasma albumin and prealbumin). METHODS: In a cohort of 324 (84 men) hospitalized elderly subjects, including 255 non-diabetic and 69 diabetic subjects, aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) together with CV risk factors. Subjects were studied over a 2-year mean follow-up period, thus enabling evaluation of long-term all-cause mortality. RESULTS: A total of 105 subjects died during the follow-up. Kaplan-Meier curves showed a significantly higher mortality in the diabetics (P=0.024). Multivariate Cox analyses differed for non-diabetic subjects and diabetics. In the former, the hazard ratio (HR) for an increase of 1 SD (with confidence intervals) was 1.36 (1.07-1.72) for PWV, 0.73 (0.52-1.01) for plasma albumin and 0.63 (0.45-0.89) for BMI. In diabetic patients, the HR was 1.60 (1.02-2.50) for leukocyte count, 1.75 (1.03-2.96) for orosomucoid levels and 0.32 (0.15-0.68) for BMI. CONCLUSION: In this very elderly population, although marginally significant on crude analysis, PWV, but not systolic or pulse pressure, was a powerful determinant of total mortality after taking into account the important role of type 2 diabetes. In diabetics, inflammation and denutrition predominated over mechanical factors.