Framingham score and micro albuminuria: Combined future targets for primary prevention?:Combined future targets for primary prevention?

Framingham score and microalbuminuria: Combined future targets for primary prevention?BackgroundRisk assessment is the cornerstone of primary prevention of cardiovascular disease. Our objective was to evaluate the prognostic value of the Framingham score in microalbuminuric subjects without a history of cardiovascular disease and whether this risk score can predict the benefit of treatment with fosinopril or pravastatin.MethodsSubjects were randomized to fosinopril 20 mg or matching placebo, and to pravastatin 40 mg or matching placebo (mean age 51 ± 12 years, 65% men, N=830). Prediction of 10-year risk for coronary heart disease by the Framingham score was performed using the risk factor categories with LDL cholesterol.ResultsAlbuminuria was correlated with Framingham score at baseline (P < 0.001). In the population with a Framingham risk score <20%, both albuminuria and Framingham risk score were independent predictors of the primary end point. A two-fold increase of albuminuria or the Framingham risk score was associated with a hazard ratio of 1.60 (95% CI 1.10–2.31), P=0.013 and 3.00 (95% CI 1.40–6.44), P=0.005, respectively. In contrast to fosinopril, pravastatin showed a significant beneficial effect on Framingham risk score after 4 years of follow-up (P < 0.001). Furthermore, the observed absolute risk reduction in cardiovascular events was greater than calculated by the Framingham risk score.ConclusionThe Framingham score is useful in microalbuminuric subjects as a prognostic tool. In addition, when considering the risk score as a target of intervention, the beneficial effects of therapies might be underestimated. Combining the Framingham score with the level of urinary albumin excretion is suggested as a primary prevention strategy with higher efficiency

Attenuation of Renovascular Damage in Zucker Diabetic Fatty Rat by NWT-03, an Egg Protein Hydrolysate with ACE- and DPP4-Inhibitory Activity

Background Dipeptidyl peptidase 4 (DPP4) and angiotensin-converting enzyme (ACE) are important target enzymes in glycemic control and renovascular protection. Here, we studied the effect of NWT-03, an egg protein hydrolysate with DPP4- and ACE-inhibitory activity, on renovascular damage in Zucker diabetic fatty (ZDF) rats. Comparisons were made to rats treated with vildagliptin (VIL), included as a positive control for the effect of DPP4 inhibition. Methods ZDF rats received NWT-03 (1 g/kg/day) or VIL (3 mg/kg/day) from 10 to 25 weeks of age. Metabolic and renal functions were assessed; the kidney was removed for histological analysis of glomerulosclerosis and expression of pro-inflammatory/fibrotic markers (RT-PCR and Western blotting); and the aorta was removed for studies of endothelium-dependent relaxation (EDR). Findings Hyperinsulinemic ZDF rats typically developed signs of type-2 diabetes and renovascular damage, as evidenced by albuminuria, glomerulosclerosis, and impaired EDR. Neither NWT-03 nor VIL improved metabolic parameters; for VIL, this was despite a 5-fold increase in glucagon-like peptide (GLP)-1 levels. NWT-03 and VIL both reduced renal interleukin (Il)-1ß/Il-13 mRNA expression and glomerulosclerosis. However, only NWT-03 additionally decreased renal tumor necrosis factor (TNF)-a mRNA and P22phox protein expression, reduced albuminuria, and restored aortic EDR. Indomethacin added to the organ bath instantly improved aortic EDR, indicating a role for cyclooxygenase (COX)-derived contractile prostanoids in opposing relaxation in ZDF rats. This indomethacin effect was reduced by NWT-03, but not by VIL, and coincided with decreased renal COX-1/2 protein expression. Conclusion and Interpretation Long-term supplementation with the egg protein hydrolysate NWT-03 attenuated renovascular damage in this preclinical rat model of type 2 diabetes. A comparison to the DPP4-inhibitor VIL suggests that the effects of NWT-03 were related to both ACE- and DPP4-inhibitory properties. The development of protein hydrolysates with a multiple-targeting strategy may be of benefit to functional food formulations

Waarde van lichte en intensieve begeleiding van patienten met hartfalen; resultaten van het COACH-onderzoek.

OBJECTIVE: To determine the efficacy of 2 nurse-directed programmes of different intensity for the counselling and follow-up of patients hospitalised for heart failure, compared with standard care by a cardiologist. DESIGN: Multicentre randomised clinical trial (www.trialregister.nl: NCT 98675639). METHOD: A total of 1023 patients were randomized after hospitalisation for heart failure to 1 of 3 treatment strategies: standard care provided by a cardiologist, follow-up care from a cardiologist with basic counselling and support by a nurse specialising in heart failure, or follow-up care from a cardiologist with intensive counselling and support by a nurse specialising in heart failure. Primary end points were the time to rehospitalisation due to heart failure or death and the number of days lost to rehospitalisation or death during the 18-month study period. Data were analysed on an intent-to-treat basis. RESULTS: Mean patient age was 71 years, 38% were women, 50% had mild heart failure and 50% had severe heart failure. During the study, 411 patients (40%) were rehospitalised due to heart failure or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (differences not significant). The time to rehospitalisation or death was similar in the 3 groups: hazard ratios for the basic and intensive support groups versus the control group were 0.96 (95% CI: 0.76-1.21; p = 0.73) and 0.93 (95% CI: 0.73-1.17; p = 0.53), respectively. The number of days lost to rehospitalisation or death was 39,960 in the control group; this number was 15% less in the intervention groups, but the difference was not significant. However, there was a trend toward lower mortality in the intervention groups. In all 3 groups, more visits occurred than planned, which may have had a considerable effect on care, notably in the control group. CONCLUSION: The results of this study indicated that the provision of additional counselling and support by a nurse specialising in heart failure as an adjuvant to intensive follow-up care provided by a cardiologist does not always lead to a reduction in rehospitalisation frequenc

Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram

The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 &times; 10-11 to 5.0 &times; 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 &times; 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation