Effect of Blood Pressure Control on Diabetic Microvascular Complications in Patiens With Hypertension and Type 2 Diabetes

WSTĘP. Badanie The Appropriate Blood Pressure Control in Diabetes (ABCD) jest prospektywnym, randomizowanym, prowadzonym metodą ślepej próby badaniem klinicznym, w którym porównywano wpływ intensywnej i umiarkowanej kontroli ciśnienia tętniczego krwi na występowanie i progresję powikłań cukrzycy typu 2. W niniejszym artykule omawiane są wyniki trwającej 5,3 roku obserwacji 470 pacjentów z nadciśnieniem tętniczym oraz wpływ intensywnego i umiarkowanego leczenia nisoldypiną w porównaniu z enalaprylem, stosowanym jako lek pierwszego wyboru w celu obniżenia ciśnienia tętniczego w nefropatii, retinopatii i w neuropatii. MATERIAŁ I METODY. 470 pacjentów, u których stwierdzono nadciśnienie tętnicze definiowane jako ciśnienie rozkurczowe o wartości wyjściowej przekraczającej 90 mm Hg, przydzielono losowo do grupy, w której nadciśnienie tętnicze leczono intensywnie, a celem terapii było osiągnięcie wartości ciśnienia rozkurczowego na poziomie 75 mm Hg albo do grupy, w której celem leczenia było uzyskanie wartości ciśnienia rozkurczowego w granicach 80–89 mm Hg. WYNIKI. W grupie leczonej intensywnie uzyskano średnią wartość ciśnienia tętniczego na poziomie 132/78 mm Hg, a w grupie leczonej w sposób konwencjonalny — 138/86 mm Hg. W ciągu 5 lat obserwacji nie stwierdzono różnic w odniesieniu do klirensu kreatyniny pomiędzy obiema grupami, a także pomiędzy grupą leczoną enalaprylem a grupą otrzymującą nisoldypinę. Po pierwszym roku leczenia hipotensyjnego klirens kreatyniny ustabilizował się zarówno u chorych leczonych intensywnie, jak i u chorych leczonych w sposób konwencjonalny, u których na początku badania stwierdzono prawidłowe wydalanie albumin z moczem lub mikroalbuminurię. Natomiast w wypadku badanych, u których występowała jawna albuminuria, obserwowano stałe obniżanie klirensu kreatyniny o 5–6 ml/min/1,73/m2 na rok przez cały czas trwania badania, niezależnie od tego, czy byli leczeni w sposób intensywny czy konwencjonalny. Nie stwierdzono też różnic pomiędzy sposobami leczenia w odniesieniu do osób, u których nastąpiła progresja z fazy normoalbuminurii do mikroalbumunurii (25% w grupie leczonej intensywnie vs 18% w grupie leczonej konwencjonalnie, p = 0,20) lub z fazy mikroalbuminurii do jawnej albuminurii (16% w grupie leczonej intensywnie vs 23% w grupie leczonej konwencjonalnie, p = 0,28). Wśród chorych leczonych intensywnie częstość zgonów była mniejsza (5,5 % vs 10,7%, p = 0,037). W ciągu 5 lat obserwacji nie stwierdzono różnic w progresji retinopatii cukrzycowej i neuropatii pomiędzy obiema grupami. Ponadto nie wykazano różnic we wpływie na retinopatię ani neuropatię pomiędzy pacjentami leczonymi nisoldypiną a chorymi otrzymującymi enalapryl. WNIOSKI. Obniżenie ciśnienia tętniczego do wartości 138/86 lub 132/78 mm Hg za pomocą nisoldypiny lub enalaprylu wpływało na stabilizację funkcjonowanie nerek u chorych na nadciśnienie tętnicze i cukrzycę typu 2, u których nie stwierdzano jawnej albuminurii podczas 5-letniej obserwacji. Bardziej intensywne leczenie nadciśnienia tętniczego powodowało zmniejszenie całkowitej śmiertelności.OBJEVTIVE. The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy. RESEARCH DESIGN AND METHODS. The 470 hypertensive subjects, defined as having a baseline diastolic blood pressure of l 90 mmHg, were randomized to intensive blood pressure control (diastolic blood pressure goal of 75 mmHg) versus moderate blood pressure control (diastolic blood pressure goal of 80–89 mmHg). RESULTS. The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group. During the 5-year follow-up period, no difference was observed between intensive versus moderate blood pressure control and those randomized to nisoldipine versus enalapril with regard to the change in creatinine clearance. After the first year of antihypertensive treatment, creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria. In contrast, patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5–6 ml · min–1 · 1.73 m–2 per year throughout the follow-up period whether they were on intensive or moderate therapy. There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria (25% intensive therapy vs. 18% moderate therapy, P = 0.20) or microalbuminuria to overt albuminuria (16% intensive therapy vs. 23% moderate therapy, P = 0.28). Intensive therapy demonstrated a lower overall incidence of deaths, 5.5 vs. 10.7%, P = 0.037. Over a 5-year follow-up period, there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy. In addition, the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy. CONCLUSIONS. Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period. The more intensive blood pressure control decreased all-cause mortality

Pulse wave velocity and carotid atherosclerosis in White and Latino patients with hypertension

<p>Abstract</p> <p>Background</p> <p>Preventive cardiology has expanded beyond coronary heart disease towards prevention of a broader spectrum of cardiovascular diseases. Ethnic minorities are at proportionately greater risk for developing extracoronary vascular disease including heart failure and cerebrovascular disease.</p> <p>Methods</p> <p>We performed a cross sectional study of Latino and White hypertension patients in a safety-net healthcare system. Framingham risk factors, markers of inflammation (hsCRP, LPpLA2), arterial stiffness (Pulse wave velocity, augmentation index, and central aortic pressure), and endothelial function (brachial artery flow-mediated dilatation) were measured. Univariate and multivariable associations between these parameters and an index of extracoronary atherosclerosis (carotid intima media thickness) was performed.</p> <p>Results</p> <p>Among 177 subjects, mean age was 62 years, 67% were female, and 67% were Latino. In univariate analysis, markers associated with carotid intima media thickness (IMT) at p < 0.25 included pulse wave velocity (PWV), augmentation index (AIx), central aortic pressure (cAP), and LpPLA₂activity rank. However, AIx, cAP, and LpPLA2 activity were not significantly associated with carotid IMT after adjusting for Framingham risk factors (all p > .10). Only PWV retained a significant association with carotid IMT independent of the Framingham general risk profile parameters (p = .016). No statistically significant interactions between Framingham and other independent variables with ethnicity (all p > .05) were observed.</p> <p>Conclusion</p> <p>In this safety net cohort, PWV is a potentially useful adjunctive atherosclerotic risk marker independent of traditional risk factors and irrespective of ethnicity.</p

Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure:Implications for Phase 2 Clinical Trials in CKD

Significance Statement: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years. These findings may help inform design of clinical trials for interventions aimed at slowing CKD progression.Background Changes in log urinary albumin-To-creatinine ratio (UACR) and GFR slope are individually used as surrogate end points in clinical trials of CKD progression. Whether combining these surrogate end points might strengthen inferences about clinical benefit is unknown.Methods Using Bayesian meta-regressions across 41 randomized trials of CKD progression, we characterized the combined relationship between the treatment effects on the clinical end point (sustained doubling of serum creatinine, GFR &lt;15 ml/min per 1.73 m2, or kidney failure) and treatment effects on UACR change and chronic GFR slope after 3 months. We applied the results to the design of Phase 2 trials on the basis of UACR change and chronic GFR slope in combination.Results Treatment effects on the clinical end point were strongly associated with the combination of treatment effects on UACR change and chronic slope. The posterior median meta-regression coefficients for treatment effects were-0.41 (95% Bayesian Credible Interval,-0.64 to-0.17) per 1 ml/min per 1.73 m2per year for the treatment effect on GFR slope and-0.06 (95% Bayesian Credible Interval,-0.90 to 0.77) for the treatment effect on UACR change. The predicted probability of clinical benefit when considering both surrogates was determined primarily by estimated treatment effects on UACR when sample size was small (approximately 60 patients per treatment arm) and follow-up brief (approximately 1 year), with the importance of GFR slope increasing for larger sample sizes and longer follow-up.Conclusions In Phase 2 trials of CKD with sample sizes of 100-200 patients per arm and follow-up between 1 and 2 years, combining information from treatment effects on UACR change and GFR slope improved the prediction of treatment effects on clinical end points.</p

Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy

Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy. Previous studies have shown that the angiotensin-converting enzyme (ACE) gene polymorphism is associated with an increased risk of vascular disease in non-diabetic patients. The present study was conducted on 509 NIDDM patients who underwent a screening test to determine their ACE genotype for the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Various baseline indices were correlated with the three ACE polymorphisms. The genotype was determined through polymerase chain reaction amplification of the angiotensin-converting enzyme polymorphism. The univariate relationship between the presence of the DD genotype with nephropathy as measured by urinary albumin excretion (UAE), and a history coronary artery disease (CAD) was then examined. Finally, a multiple model for each UAE and CAD was created so as to determine the independent effects of the presence of the DD genotype on each diabetic complication. Univariately, the presence of the DD genotype was associated with diabetic nephropathy. Furthermore, in a multiple model predicting diabetic nephropathy, the presence of the DD genotype was independently associated with diabetic nephropathy (odds ratio = 2.8, 95% confidence interval 1.4 to 5.5) but not CAD. Thus, the ACE DD genotype in 509 non-Hispanic white NIDDM patients in a metropolitan area in the U.S. was independently associated with the presence of diabetic nephropathy and, therefore, may be potentially used as a marker for NIDDM patients at risk for developing diabetic nephropathy

A Controlled Trial of Mobile Short Message Service among Participants in a Rural Cardiovascular Disease Prevention Program

The statewide Colorado Healthy Heart Solutions (CHHS) program provides cardiovascular disease (CVD) risk factor screening and education to the medically underserved and has been shown to improve CVD risk profiles. We aimed to enhance its effectiveness through addition of a mobile health (mHealth) intervention using SMS messaging (termed Cardio SMS). We conducted a prospective, non-randomized controlled pilot trial of this intervention implemented at 5 rural program sites (number of participants N = 204) compared with a contemporaneous propensity-score matched control group from 14 CHHS sites not receiving the intervention (N = 408) between 2012 and 2014. All participants were free of CVD at baseline, and follow-up time was 12-months. The primary outcome was program engagement, defined as the number of completed interactions with the program during the entire follow-up period. Secondary outcomes were program retention, defined as any interaction during the last two months of the study; change in self-reported healthy behaviors (physical activity, weight loss, smoking cessation, fat intake); and change in CVD risk factors. There were trends for differences between groups across multiple outcomes, but most did not reach statistical significance, except for a greater decrease in self-reported fat intake in the intervention vs. control groups (26.3% vs 10.6%, P = 0.001). In addition, a subset of surveyed participants who viewed the SMS messages as motivating showed greater program retention (P = 0.03). Given the relative ease and scalability of SMS interventions in rural underserved communities, further study of SMS as part of multicomponent strategies for CVD prevention is warranted

Pulse wave velocity and carotid atherosclerosis in white and Latino patients with hypertension.

BackgroundPreventive cardiology has expanded beyond coronary heart disease towards prevention of a broader spectrum of cardiovascular diseases. Ethnic minorities are at proportionately greater risk for developing extracoronary vascular disease including heart failure and cerebrovascular disease.MethodsWe performed a cross sectional study of Latino and White hypertension patients in a safety-net healthcare system. Framingham risk factors, markers of inflammation (hsCRP, LPpLA2), arterial stiffness (Pulse wave velocity, augmentation index, and central aortic pressure), and endothelial function (brachial artery flow-mediated dilatation) were measured. Univariate and multivariable associations between these parameters and an index of extracoronary atherosclerosis (carotid intima media thickness) was performed.ResultsAmong 177 subjects, mean age was 62 years, 67% were female, and 67% were Latino. In univariate analysis, markers associated with carotid intima media thickness (IMT) at p&lt;0.25 included pulse wave velocity (PWV), augmentation index (AIx), central aortic pressure (cAP), and LpPLA2 activity rank. However, AIx, cAP, and LpPLA2 activity were not significantly associated with carotid IMT after adjusting for Framingham risk factors (all p&gt;.10). Only PWV retained a significant association with carotid IMT independent of the Framingham general risk profile parameters (p=.016). No statistically significant interactions between Framingham and other independent variables with ethnicity (all p&gt;.05) were observed.ConclusionIn this safety net cohort, PWV is a potentially useful adjunctive atherosclerotic risk marker independent of traditional risk factors and irrespective of ethnicity