We respond to recent correspondence relating to the Conduit Artery Function Evaluation study (CAFE), 1 published in Circulation earlier this year.We thank Drs Nieminen, Kahonen, and Kobie for their remarks and suggestions. We agree that increased stroke volume at lower heart rates should be considered as a contributor to the elevated pulse pressure (PP) seen with atenolol-based treatment in the CAFE study. We did not assess stroke volume, and further studies are required to define the impact of blood pressure (BP)-lowering therapies on stroke volume and its contribution to central aortic pressures. Nevertheless, our data do suggest an important role for increased wave reflections in determining higher central aortic pressures with atenolol-based when compared with amlodipine-based treatment. Indeed, the higher central but not brachial PP with atenolol-based therapy in the CAFE study supports the hypothesis that the main driver of differential central aortic pressures was drug effects on pressure wave reflections rather than changes in stroke volume.We agree with Drs Safar and Fournier that the findings of the CAFE study are consistent with their report of differential drug effects on central aortic pressures in the Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind Study (REA-SON). 2 We concur with the view that vascular structural changes are likely to make an important contribution to the long-term hemodynamic effects of BP-lowering therapy, especially wave reflection, and we suggested in our article that different BPlowering treatments may modify central aortic pressures and hemodynamics through differential effects on vascular structure. 1 The fact that the most beneficial effects on central aortic pressure have been observed with vasodilator therapy, in contrast to ␤-blockade, supports the view that a reduction in vascular resistance, by vasodilation and subsequent vascular remodeling, is an important determinant of reduced wave reflection and central aortic pressure, thereby defining the characteristics of optimal BP-lowering therapy.Cameron and colleagues are concerned that the data in their article 3 may have been misinterpreted. We clarify that our reference to their work related to the accuracy and validation of the transfer function rather than the derivation of central aortic pressures, which are prone to and dependent on the same level of inaccuracy as the measurement of brachial BP by cuff sphygmomanometry.We thank Dr Dart et al for their comments and interest in our study but would like to point out fundamental differences between the design and objectives of the CAFE study and The Australian National Blood Pressure Study 2 (ANBP2). substudy of central aortic pressures. 4 The prespecified primary objective 5 of the CAFE study was to examine the hypothesis that 2 different BP-lowering regimens would have different effects on derived central arterial pressures and hemodynamics despite similar effects on brachial pressures. This was convincingly demonstrated by the findings of ...

Societies CVD risk-assessment programme/chart. Optimal cholesterol lowering should reduce the total cholesterol by 25% or LDL-cholesterol by 30% or achieve a total cholesterol of o4.0 mmol/l or LDL-cholesterol of o2.0 mmol/l, whichever is the greatest reduction (A). Glycaemic control should be optimised in people with diabetes, for example, HbA1c o7% (A). Advice is provided on the clinical management of hypertension in specific patient groups, that is, the elderly, ethnic minorities, people with diabetes mellitus, chronic renal disease, and in women (pregnancy, oral contraceptive use and hormone-replacement therapy). Suggestions for the improved implementation and audit of these guidelines in primary care are provided.

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BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.

for the UMPIRE Collaborative Group IMPORTANCE Most patients with cardiovascular disease (CVD) do not take recommended medications long-term. The use of fixed-dose combinations (FDCs) improves adherence in several clinical areas. Previous trials of cardiovascular FDCs have assessed short-term effects compared with placebo or no treatment. OBJECTIVE To assess whether FDC delivery of aspirin, statin, and 2 blood pressure-lowering agents vs usual care improves long-term adherence to indicated therapy and 2 major CVD risk factors, systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C). DESIGN, SETTING, AND PARTICIPANTS The UMPIRE trial, a randomized, open-label, blinded-end-point trial among 2004 participants with established CVD or at risk of CVD enrolled July 2010-July 2011 in India and Europe. The trial follow-up concluded in July 2012.INTERVENTIONS Participants were randomly assigned (1:1) to an FDC-based strategy (n=1002) containing either (1) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol or (2) 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide or to usual care (n=1002). MAIN OUTCOMES AND MEASURESAdherence to medication (defined as self-reported use of antiplatelet, statin, and Ն2 BP-lowering medications) and changes in SBP and LDL-C from baseline.RESULTS At baseline, mean BP was 137/78 mm Hg, LDL-C was 91.5 mg/dL, and 1233 (61.5%) of 2004 participants reported use of antiplatelet, statin, and 2 or more BP-lowering medications. Median follow-up was 15 months (interquartile range, 12-18 months). The FDC group had improved adherence vs usual care (86% vs 65%; relative risk [RR] of being adherent, 1.33; 95% CI, 1.26-1.41; P < .001) with concurrent reductions in SBP (−2.6 mm Hg; 95% CI, −4.0 to −1.1 mm Hg; P < .001) and LDL-C (−4.2 mg/dL; 95% CI, −6.6 to −1.9 mg/dL; P < .001) at the end of the study. Although there was consistency of effects across predefined subgroups, evidence existed of larger benefits in patients with lower adherence at baseline. In this subgroup of 727 participants (36%), adherence at the end of study was 77% vs 23% (RR, 3.35; 95% CI, 2.74-4.09; P < .001 for interaction), SBP was reduced by 4.9 mm Hg (95% CI 7.3-2.6 mm Hg; P = .01 for interaction), and LDL-C was reduced by 6.7 mg/dL (95% CI, 10.5-2.8 mg/dL; P = .11 for interaction). There were no significant differences in serious adverse events or cardiovascular events (50 [5%] in the FDC group and 35 [3.5%] in the usual care group; RR, 1.45; 95% CI, 0.94-2.24; P=.09) between the groups.CONCLUSIONS AND RELEVANCE Among patients with or at high risk of CVD, use of an FDC strategy for blood pressure, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in SBP and LDL-C.

Abstract-Abnormalities of the retinal microcirculation are found in hypertension and diabetes and predict cardiovascular mortality. This study examined the relationship between abnormalities of the retinal microvasculature and death from ischemic heart disease (IHD) and stroke. A population-based, nested case-control study was undertaken within the Beaver Dam Eye Study. Subjects (43 to 74 years) who died of IHD (nϭ126) or stroke (nϭ28) over a 10-year period were age and gender matched with controls subjects (nϭ528; case:control matching, Ϸ1:4). Retinal photographs of cases and controls were digitized and analyzed using a computer-based technique. Increased risk of IHD death was associated with a suboptimal relationship of arteriolar diameters at bifurcation (Pϭ0.02 unadjusted) and decreased retinal arteriolar tortuosity (Pϭ0.011 unadjusted). These associations remained significant after adjustment for age, sex, past history of cardiovascular disease, and other known cardiovascular risk factors. Increased arteriolar length:diameter ratio, a measure of generalized arteriolar narrowing, was associated with increased stroke mortality (Pϭ0.02 unadjusted). This association was independent of age and gender but was attenuated by adjustment for systolic blood pressure (Pϭ0.15). Other quantitative measures of the retinal microvascular network (eg, venular tortuosity and arteriolar and venular bifurcation angle) were not associated with death from IHD or stroke. Retinal microvascular abnormalities are predictive of death from IHD and stroke. A detailed assessment of the retinal microvascular network from digitized photographs may be useful in the noninvasive assessment of target organ damage and cardiovascular risk.

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