Causes of death in women with breast cancer: a risks and rates study on a population-based cohort.

Introduction: The increasing survival of patients with breast cancer has prompted the assessment of mortality due to all causes of death in these patients. We estimated the absolute risks of death from different causes, useful for health-care planning and clinical prediction, as well as cause-specific hazards, useful for hypothesis generation on etiology and risk factors. Materials and methods: Using data from population-based cancer registries we performed a retrospective study on a cohort of women diagnosed with primary breast cancer. We carried out a competing-cause analysis computing cumulative incidence functions (CIFs) and cause-specific hazards (CSHs) in the whole cohort, separately by age, stage and registry area. Results: The study cohort comprised 12,742 women followed up for six years. Breast cancer showed the highest CIF, 13.71%, and cardiovascular disease was the second leading cause of death with a CIF of 3.60%. The contribution of breast cancer deaths to the CIF for all causes varied widely by age class: 89.25% in women diagnosed at age <50 years, 72.94% in women diagnosed at age 50-69 and 48.25% in women diagnosed at age ≥70. Greater CIF variations were observed according to stage: the contribution of causes other than breast cancer to CIF for all causes was 73.4% in women with stage I disease, 42.9% in stage II-III and only 13.2% in stage IV. CSH computation revealed temporal variations: in women diagnosed at age ≥70 the CSH for breast cancer was equaled by that for cardiovascular disease and "other diseases" in the sixth year following diagnosis, and an early peak for breast cancer was identified in the first year following diagnosis. Among women aged 50-69 we identified an early peak for breast cancer followed by a further peak near the second year of follow-up. Comparison by geographic area highlighted conspicuous variations: the highest CIF for cardiovascular disease was more than 70% higher than the lowest, while for breast cancer the highest CIF doubled the lowest. Conclusion: The integrated interpretation of absolute risks and hazards suggests the need for multidisciplinary surveillance and prevention using community-based, holistic and well-coordinated survivorship care models.

Effect of furosemide on left ventricular mass in non-dialysis chronic kidney disease patients: a randomized controlled trial.

BACKGROUND: In chronic kidney disease (CKD), loop diuretics correct volume-dependent hypertension, but their effect on left ventricular mass index (LVMI) is unknown. METHODS: Forty hypertensive CKD patients (estimated creatinine clearance 60-15 mL/min/1.73 m²), treated with renin-angiotensin system (RAS) inhibitors, were randomized to receive furosemide or non-diuretic antihypertensive treatment (control group). Office blood pressure (BP) < 130/80 mmHg was pursued in both groups. Primary end point was the reduction of LVMI after 52 weeks. Secondary aims were to verify safety related to furosemide treatment and its effects on ambulatory and clinic BP and body fluid volumes. RESULTS: Office BP similarly declined in the furosemide group (from 161 ± 14/80 ± 10 to 139 ± 14/74 ± 8 mmHg) and in controls (from 159 ± 16/81 ± 10 to 137 ± 16/75 ± 10 mmHg). We detected a greater reduction (P = 0.013) of LVMI in patients receiving furosemide (-7.9, IQR from -15.8 to -1.4 g/h(2.7)) than in controls (0.0, IQR from -6.2 to + 9.5 g/h(2.7), P = 0.013). Bio-impedance analysis-derived extracellular water (ECW) significantly decreased in furosemide-treated patients (from 18.7 ± 3.9 to 17.7 ± 3.3 L) while remained unchanged in the control group (from 19.5 ± 2.2 to 19.6 ± 1.9 L). Absolute change of LVMI correlated with changes of ECW in furosemide-treated patients (r = 0.458, P = 0.042) but not in controls. In the furosemide group, no patient experienced side effects requiring drug withdrawal. CONCLUSIONS: In hypertensive CKD patients treated with RAS inhibitors, add-on furosemide efficaciously reduces LVMI independently from BP changes. The effect is possibly mediated by better control of volume expansion.

Dietary sodium intake modulates myocardial relaxation responsiveness to angiotensin II.

Dietary sodium alters renovascular responsiveness to angiotensin II (Ang II) in normal subjects. Evidence supports a connection among dietary sodium, the rennin-angiotensin system, and myocardial function. The authors hypothesized that a similar relationship would exist in the heart, and that the pattern of responses would be qualitatively similar to the renal vasculature. Thirteen healthy volunteers (aged 38.6 +/- 4 years) entered a 2 week crossover design study (week 1, high sodium diet [HS] > 200 mmol Na/day; week 2, low sodium diet [LS], < 10 mmol Na/day) to investigate the influence of dietary sodium and Ang II on myocardial relaxation and renal blood flow (RBF). At the end of each study week, the authors assessed diastolic function (myocardial relaxation velocities [E'] using tissue Doppler imaging) and RBF (para-aminohippurate clearance) at baseline and after infusion of Ang II (3 ng/kg/min x 45 min). On HS diet, E' and RBF were higher than on LS diet (E' 14.0 +/- 1.2 vs 12.6 +/- 1.0 cm/s, P = 0.02; RBF 596 +/- 24 vs 563 +/- 26 mL/min, P = 0.02). Dietary sodium significantly modulated E' and RBF responsiveness to Ang II infusion in like manner. HS was associated with increased responsiveness compared with a blunted LS response (HS DeltaE' -1.4 +/- 0.4 cm/s vs LS DeltaE' -0.1 +/- 0.3 cm/s, P = 0.02; HS DeltaRBF -135.2 +/- 13.2 vs LS DeltaRBF -62.5 +/- 10.1 mL/min, P < 0.01). The authors describe for the first time that dietary sodium modulates myocardial relaxation and responsiveness to Ang II. It is important to consider dietary sodium intake when assessing diastolic function. Ang II may play a role in the interaction between dietary sodium and myocardial relaxation. Future research will investigate whether abnormalities in these mechanisms play a role in disorders of diastolic function.