Selection bias of elderly patients with chronic angina referred for catheterization.

BACKGROUND: Registry patients are generally older and more sick than patients enrolled in trials questioning the generalizability of trial results. We assessed whether such a selection bias also exists in elderly patients with chronic angina referred for catheterization. METHODS AND RESULTS: All 119 patients age>or=75 years with Trial of Invasive versus Medical Therapy in the Elderly (TIME) inclusion but no major exclusion criteria referred for catheterization during the TIME trial inclusion period in four TIME centers were registered and followed-up for one year. Registry patients differed from the 188 trial patients in the same hospitals in that they were younger, somewhat more frequently male, with less antianginal drugs and studied more often after acute chest pain at rest but with more comorbidities than study patients. Left ventricular ejection fraction and vessel disease were similar. One year mortality was 11.4% in registry and 9.6% in invasive TIME patients but differences disappeared after adjustment for baseline differences. Symptomatic status after one year was similar too. CONCLUSIONS: In elderly patients with chronic angina, a bias in the selection for invasive management exists which seems different from that reported in younger patient settings. After adjustment for these selection factors, however, one-year outcome was remarkably similar in registry and trial patients.

Relation of cyclosporine blood levels to adverse effects on lipoproteins.

Hyperlipidemia is common in renal allograft recipients. To elucidate the role of cyclosporine in posttransplant hyperlipidemia, we measured lipids, lipoprotein lipids, and apolipoproteins of thirty-five renal allograft recipients and evaluated their relation to trough cyclosporine blood levels. All patients were on a triple immunosuppressive regimen with equal doses of prednisone and azathioprine, and had stable graft function. Cyclosporine blood levels were significantly correlated to total plasma cholesterol (P = 0.028), low-density lipoprotein cholesterol (P = 0.022), apolipoprotein B (P = 0.017), and the cholesterol/high-density lipoprotein cholesterol ratio (P < 0.002), but not to plasma triglycerides. Significant inverse correlations were found between cyclosporine blood levels and high-density lipoprotein cholesterol (P = 0.034), high-density lipoprotein3 cholesterol (P = 0.025), and apolipoprotein A-1 (P = 0.047), but not high-density lipoprotein2 cholesterol. The independent relation of cyclosporine blood levels to each of the measured lipid parameters was investigated by a stepwise regression model including age, body mass index, interval from transplantation, diabetes mellitus, plasma creatinine, and intake of diuretics and beta-blockers. After correction for these 7 variables, cyclosporine blood levels remained significantly associated with high-density lipoprotein cholesterol, high-density lipoprotein3 cholesterol, apolipoprotein A-1, apolipoprotein B, low-density lipoprotein cholesterol, and the cholesterol/high-density lipoprotein cholesterol ratio. These data suggest that cyclosporine causes atherogenic dyslipidemia.

Role of RAS inhibition in the regulation of Cu/Zn-SOD in the cardiac and peripheral arterial beds in humans.

Inhibition of the renin-angiotensin system (RAS) improves hemodynamics and may ameliorate oxidative stress in heart failure (HF). Through activation of nicotinamide adenine dinucleotide phosphate oxidase, angiotensin II induces superoxide, which is primarily cleared by cytosolic copper-zinc superoxide dismutase (Cu/Zn-SOD). We examined the interdependency of hemodynamics and levels of Cu/Zn-SOD and oxidized low-density lipoprotein (oxLDL) in HF patients, using a randomized, double-blinded, crossover design to compare (i) the outcomes of single-agent therapy with either benazepril or valsartan alone vs. the combination thereof and (ii) the outcome of single-agent treatment with benazepril vs. single-agent treatment with valsartan. After each treatment, arterial (ART) and coronary sinus (CS) blood samples were collected. Cu/Zn-SOD and oxLDL levels were higher in CS samples than in ART samples. Furthermore, patients under combined treatment exhibited the highest CS levels of Cu/Zn-SOD, whereas there was no significant difference between the groups on either benazepril or valsartan alone. This finding suggests an augmentation of the cardiac antioxidative potential under more complete RAS inhibition. Cu/Zn-SOD and oxLDL levels correlated with measures of afterload rather than preload, which in turn suggests a beneficial effect of afterload reduction on oxidative stress in HF.

Improvements in physical and mental domains of quality of life by anti-ischaemic drug and revascularisation treatment in elderly men and women with chronic angina.

BACKGROUND: The severity of angina is related to a reduction in global quality of life (QoL), which may be improved by anti-ischaemic treatment. It is not known, however, whether improvements relate only to physical or also to mental and social domains of QoL and whether women benefit in a similar way to men. OBJECTIVES: To relate improvements in angina severity through anti-ischaemic treatment to physical and mental domains of QoL in elderly men and women and to assess differences in this relation between the sexes. METHODS: Angina severity and full assessment of QoL by structured, self-administered and validated questionnaires were measured prospectively at baseline and after 6 months' optimal drug or revascularisation treatment in all 301 patients of the Trial of Invasive versus Medical therapy in Elderly (TIME) patients with chronic angina. RESULTS: At baseline, angina severity correlated significantly with physical domains of QoL (trend test at least p<0.02) and daily activities (p = 0.05). At similar angina levels, women had significantly lower QoL scores than men. With anti-ischaemic treatment, physical as well as mental and social QoL domains and daily activities improved, together with a relief in angina (trend tests at least p<0.02). This was true for women and men and was more pronounced after revascularisation than with medical treatment. CONCLUSIONS: These findings confirm the relation between angina severity and physical limitation. In addition, they show that anti-ischaemic treatment not only relieves angina and improves physical components of QoL but also improves mental and social domains. This is true for women as well as for men despite the lower overall scores for women.

[An uncommon case of lupus]. / Ein aussergewöhnlicher Fall von Lupus.

A 44-year-old patient was referred with weight loss of some 6 kg in two months, weakness and diarrhoea. According to the criteria of the American College of Rheumatology (ACR), systemic lupus erythematosus (SLE) was diagnosed: photodermatosis, nephropathy, and pancytopenia with positive antinuclear antibodies and antibodies against native DNA. In addition, adrenal failure was diagnosed with hyponatraemia, relapsing fever, low baseline cortisol and impaired response to ACTH stimulation. Clinical features of SLE may obscure signs of adrenal insufficiency, and hence, diagnosis is jeopardized. SLE combined with Addition's disease is rare. In some patients with both disorders, antiphospholipid antibodies, as found in our patient, are considered responsible for the development of Addison's disease. Possible pathogenetic mechanisms such as adrenal haemorrhage or (micro)thrombosis are discussed. The patient's condition significantly improved under steroid therapy. The progression of renal insufficiency (histology: mesangioproliferative glomerulonephritis), however, required additional immunosuppression with cyclophosphamide.