Showing papers by "Suzanne Oparil published in 2013"

Prevalence of apparent treatment-resistant hypertension among individuals with CKD.

Abstract: Summary Background and objectives Apparent treatment-resistant hypertension is defined as systolic/diastolic BP≥140/90 mmHg with concurrent use of three or more antihypertensive medication classes or use of four or more antihypertensive medication classes regardless of BP level. Design, setting, participants, & measurements The prevalence of apparent treatment-resistant hypertension among Reasons for Geographic and Racial Differences in Stroke study participants treated for hypertension ( n =10,700) was determined by level of estimated GFR and albumin-to-creatinine ratio, and correlates of apparent treatment-resistant hypertension among those participants with CKD were evaluated. CKD was defined as an albumin-to-creatinine ratio≥30 mg/g or estimated GFR 2 . Results The prevalence of apparent treatment-resistant hypertension was 15.8%, 24.9%, and 33.4% for those participants with estimated GFR≥60, 45–59, and 2 , respectively, and 12.1%, 20.8%, 27.7%, and 48.3% for albumin-to-creatinine ratio 2 , respectively, versus ≥60 ml/min per 1.73 m 2 and 1.54 (1.39 to 1.71), 1.76 (1.57 to 1.97), and 2.44 (2.12 to 2.81) for albumin-to-creatinine ratio levels of 10–29, 30–299, and ≥300 mg/g, respectively, versus albumin-to-creatinine ratio Conclusions This study highlights the high prevalence of apparent treatment-resistant hypertension among individuals with CKD.

Relationships between metrics of visit-to-visit variability of blood pressure

Abstract: This paper examines relationships between metrics of visit-to-visit variability (VVV) of blood pressure (BP) to determine which metrics should be calculated in studies of the association of VVV with health outcomes. We examined correlation and agreement between quintiles for standard deviation (s.d.), standard deviation independent of the mean (SDIM), coefficient of variation (CV), successive variation (SV), average real variability (ARV), range, maximum, peak size and trough size of systolic BP in the Trial of Preventing Hypertension placebo arm (n=288). The average age of participants was 48 years. Mean systolic BP was 133.5 mm Hg. VVV metrics were all significantly correlated (P<0.001). Correlations between s.d., SDIM, CV and range and between ARV and SV were⩾0.90. Kappa statistics between quintiles of SD, SDIM, CV and range and between ARV and SV were ⩾0.80. In studies of the relationship of VVV with health outcomes, we recommend reporting results for one of the metrics of overall variability (s.d., SDIM, CV), one of the metrics of variability between consecutive visits (SV, ARV), and one or more of the metrics of extreme values at a single visit (maximum, peak size, trough size).

Association Between Antihypertensive Medication Adherence and Visit-to-Visit Variability of Blood Pressure

Abstract: It has been hypothesized that high visit-to-visit variability (VVV) of systolic blood pressure (SBP) may be the result of poor antihypertensive medication adherence. The authors studied this association using data from 1391 individuals taking antihypertensive medication selected from a large managed care organization. The 8-item Morisky Medication Adherence Scale, administered during 3 annual surveys, captured self-report adherence, with scores<6, 6 to <8, and 8 representing low, medium. and high adherence, respectively. The mean (standard deviation [SD]) for SD of SBP across study visits was 12.9 (4.4), 13.5 (4.8), and 14.1 (4.5) mm Hg in participants with high, medium, and low self-reported adherence, respectively. After multivariable adjustment and compared with those with high self-report adherence, SD of SBP was 0.60 (95% confidence interval, 0.13-1.07) and 1.08 (95% confidence interval, 0.29-1.87) mm Hg higher among participants with medium and low self-report adherence, respectively. Results were consistent when pharmacy fill was used to define adherence. These data suggest that low antihypertensive medication adherence explains only a small proportion of VVV of SBP.

Effect of antihypertensive therapy on ventricular-arterial mechanics, coupling, and efficiency

Abstract: Aims To investigate the effect of antihypertensive therapy on ventricular–arterial mechanics, coupling, and efficiency in early-stage hypertension. Methods and results We studied 527 participants from two clinical trials assessing the effect of blood pressure lowering on diastolic function. Participants were aged ≥45 years with early-stage hypertension, no heart failure, ejection fraction (EF) ≥50%, and diastolic dysfunction using Doppler echocardiography. Effective arterial afterload and its components were assessed along with measures of left ventricular (LV) structure and function prior to and after 24–38 weeks of antihypertensive therapy. Systolic blood pressure decreased from 154 ± 18 to 137 ± 15 mmHg at follow-up. Blood pressure reduction was associated with decreases in ventricular and arterial stiffness, improvements in systemic arterial compliance and resistance, enhanced LV ejection, and reduction in cardiac work (all P < 0.001). Changes in Ea/Ees ratio were inversely correlated with those in EF ( r = −0.25; P < 0.001), stroke work index ( r = −0.13; P = 0.007), and LV efficiency ( r = −0.98; P < 0.001); and directly related to changes in mitral E / e ′ ( r = 0.12; P = 0.01). Adjusting for age and blood pressure change, women and obese individuals had less enhancement in ventricular–arterial coupling and efficiency compared with men and non-obese individuals ( P = 0.04 and 0.007, respectively). Conclusion Antihypertensive therapy reduces arterial and ventricular stiffness, enhances ventricular–arterial coupling, reduces cardiac work, and improves LV efficiency, systolic, and diastolic function. Attenuated responses in women and among obese subjects suggest that structure–function changes may be less reversible in these groups, possibly explaining their greater susceptibility to ultimately develop heart failure.

The contributions of unhealthy lifestyle factors to apparent resistant hypertension: findings from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Abstract: Objectives:Unhealthy lifestyle factors may contribute to apparent treatment resistant hypertension (aTRH). We examined associations of unhealthy lifestyle factors with aTRH in individuals taking antihypertensive medications from three or more classes.Methods:Participants (n = 2602) taking three or m

Mortality and Morbidity During and After Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Results by Sex

Abstract: To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women There were no significant treatment sex interactions These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men Clinical Trial Registration- clinicaltrialsgov; Identifier: NCT00000542

2013 European Society of Hypertension/European Society of Cardiology Hypertension Guidelines

Abstract: The first European Guidelines on Hypertension were issue in 2003 and published in the Journal of Hypertension. The publication became the most cited paper in medical literature in 2003 and 2004. Th...

Long‐Term Follow‐Up of Moderately Hypercholesterolemic Hypertensive Patients Following Randomization to Pravastatin vs Usual Care: The Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT‐LLT)

Abstract: The Lipid Lowering Trial component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT) was a multi-center randomized trial comparing usual care versus treatment with an HMG CoA-reductase inhibitor (pravastatin) in a moderately hypercholesterolemic treated hypertensive cohort with other coronary heart disease (CHD) risk factors, including preexisting cardiovascular disease (CVD).1 After an average of 4.8 years of follow-up, there was no difference in the primary endpoint of all-cause mortality (HR 0.99; 95% confidence interval [CI], 0.89-1.11; P=.88), and a non-significant lowering of secondary CHD endpoints of nonfatal myocardial infarction (MI) and CHD death (HR 0.91; 95% CI, 0.79-1.04; P=.16).2 Fatal and nonfatal stroke was also non-significantly reduced in the pravastatin group (HR 0.91; 95% CI, 0.75-1.09; P=.31). These results, which contrasted with those of most statin trials,3 were attributed to the diminished power resulting from treatment crossovers and a consequently smaller than expected differential reduction in cholesterol levels. There was no heterogeneity of ALLHAT-LLT primary and secondary outcomes by age, sex, previous history of CHD, history of diabetes or baseline level of cholesterol.2 However, significant differences were observed between Blacks and non-Blacks for secondary outcomes of CHD and stroke. For stroke, pravastatin showed no benefit in Blacks but was protective in non-Blacks (HR 1.12; 95% CI 0.86-1.48; vs. 0.74; 95% CI 0.57-0.96; P for interaction=.03);4 whereas for CHD events pravastatin was protective in Blacks but not in non-Blacks (HR 0.71; 95% CI 0.57-0.90; P=.005 vs. 1.00; 95% CI 0.85-1.19; P=.095, P for interaction=.02).4,5 For CHD events, in-depth analyses have shown that these differences were not accounted for by baseline differences in risk factors, adherence during trial, or achieved blood pressure (BP) and lipid lowering.5 Because Blacks have been under-represented in statin trials and ALLHAT-LLT remains one of the largest statin trials with a substantial proportion of Black participants (38%), further exploration of these unexplained findings is of great scientific interest. The purpose of this paper is to report 10-year mortality and morbidity of ALLHAT-LLT participants using in-trial data, plus post-trial data from administrative databases (National Death Index, Social Security Administration, Center for Medicare and Medicaid Services, and United States Renal Data System)4,6 in order to assess long-term effects of treatment with pravastatin versus usual care. We will focus in particular on whether Black vs. non-Black racial differences in CHD and stroke observed during trial persisted or attenuated. Further, we will examine whether differences emerge for outcomes that were not statistically different at trial's end.

Changes in Cardiovascular Risk Associated With Phentermine and Topiramate Extended-Release in Participants With Comorbidities and a Body Mass Index ≥27 kg/m2

Abstract: The aim of this analysis was to evaluate changes in cardiovascular risk factors in obese patients with dyslipidemia and/or hypertension receiving phentermine (PHEN) and topiramate extended-release (TPM ER). In the 56-week, randomized, double-blind, placebo-controlled, multicenter CONQUER trial, PHEN/TPM ER demonstrated significant weight loss compared with placebo in overweight or obese participants with ≥2 weight-related co-morbidities. Participants with body mass indexes of 27 to 45 kg/m 2 were randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg, or PHEN 15 mg/TPM ER 92 mg; participants also received lifestyle modification counseling. Primary end points were percentage weight loss and the proportion of participants achieving ≥5% weight loss. Additional end points were changes in lipid variables in the dyslipidemia population and blood pressure in the hypertensive population, stratified by treatment and magnitude of weight loss. PHEN/TPM ER produced significantly greater dose-related mean percentage weight loss compared with placebo in the subgroups of participants with dyslipidemia and those with hypertension. Regardless of treatment group assignment, participants with dyslipidemia who lost ≥5% of their baseline weight experienced significantly greater reductions in triglycerides (−14.5% to −39.8%), and in non–high-density lipoprotein cholesterol (−9.4% to −14.8%) than those losing

Randomized Study of Antihypertensive Efficacy and Safety of Combination Aliskiren/Valsartan vs Valsartan Monotherapy in Hypertensive Participants With Type 2 Diabetes Mellitus

Abstract: In this double-blind study, 1143 hypertensive participants with type 2 diabetes and stage 1 or 2 chronic kidney disease (CKD) were randomized to receive combination aliskiren/valsartan 150/160 mg or valsartan 160 mg monotherapy for 2 weeks, with force-titration to 300/320 mg and 320 mg, respectively, for another 6 weeks. Ambulatory blood pressure (ABP), the primary outcome, was available for 665 participants. Reductions from baseline to week 8 in 24-hour ABP were -14.1/-8.7 mm Hg with aliskiren/valsartan vs -10.2/-6.3 mm Hg with valsartan (P 40 mg/dL or serum creatinine values>2.0 mg/dL. There were no confirmed cases of serum potassium values≥6.0 mEq/L. Combination aliskiren/valsartan has additive effects on blood pressure reduction and tolerability similar to valsartan in hypertensive/diabetic participants with early-stage (stages 1 and 2) CKD.

Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction

Abstract: The endothelium is a dynamic component of the cardiovascular system that plays an important role in health and disease. This study tested the hypothesis that targeted delivery of endothelial cells ...

Ovarian hormones and vascular disease.

Abstract: Purpose of review Observational studies have shown benefit of hormone therapy, particularly estrogen, in women who begin treatment in the perimenopausal/early postmenopausal period, whereas randomized controlled trials of such therapy in older postmenopausal women have reported harm. These apparently paradoxical findings have led to the 'timing hypothesis' which proposes that estrogen signaling is altered in older women, converting vasoprotective to vasotoxic effects. We reviewed recent literature on age-dependent effects of hormones (particularly estrogen) on the vasculature of women and the fundamental cellular/molecular mechanisms responsible for those effects. Recent findings Observational studies have shown that early menopause is associated with adverse cardiovascular disease outcomes and that starting hormone therapy in the perimenopausal period reduces these outcomes. Mechanistic studies have shown that estrogen modulates injury-induced inflammation, growth factor expression, and oxidative stress in arteries and vascular smooth muscle cells isolated from young women but that these vasoprotective mechanisms are lost in women who are aged and/or deprived of estrogen for prolonged periods of time. Summary The vasoprotective effects of estrogen are age-dependent and disappear with aging and/or estrogen deprivation. Future studies designed to preserve the vasoprotective effects of estrogen in older women are needed and may lead to innovative approaches to improving women's cardiovascular health.

Olmesartan/Amlodipine/Hydrochlorothiazide in Obese Participants With Hypertension: A TRINITY Subanalysis

Abstract: The objective of this prespecified TRINITY study subgroup analysis was to assess the efficacy and safety of triple-combination treatment with olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg vs the component dual-combination treatments in obese (body mass index [BMI] ≥30 kg/m2) and nonobese (BMI <30 kg/m2) hypertensive participants The double-blind treatment period primary end point was the least-squares (LS) mean reduction in seated diastolic BP (SeDBP) at week 12 (end of the double-blind period) Of the 2492 randomized participants, 1555 (624%) had BMI ≥30 kg/m2 Irrespective of BMI, triple-combination treatment resulted in greater LS mean reductions in seated BP (SeBP) (≥30 kg/m2, 67–105/45–73 mm Hg; <30 kg/m2, 51–86/25–60 mm Hg [P<005] vs dual-combination treatments for both subgroups) at week 12 Furthermore, triple-combination treatment enabled a greater proportion of participants to reach BP goal vs the dual-combination treatments (≥30 kg/m2, 62% vs 31%–46% [P<0001]; <30 kg/m2, 69% vs 41%–55% [P<005]) at week 12 SeBP reduction and goal attainment (≥30 kg/m2, 63%; <30 kg/m2, 67%) was maintained through week 52/early termination Triple-combination treatment was well tolerated in both BMI subgroups

Blood pressure lowering effect of renal sympathetic denervation or placebo? - building expectations for Symplicity-HTN 3

Abstract: More than 10% of patients treated for hypertension have persistently uncontrolled blood pressure (BP) despite prescription of antihypertensive drugs (1). Renal sympathetic denervation is an old concept that has been re-introduced as a new treatment for hypertension that is apparently resistant to drug treatment (2). Patients considered eligible for this procedure populate the high end of the BP spectrum, where, for whatever reason, pharmacologic treatment has failed to produce adequate BP control. Recent data suggest that patients suspected of having “ resistant hypertension ” in fact represent a mixed group that includes those with white coat hypertension, secondary forms of hypertension, inadequate dosing of medication, and poor adherence to prescribed antihypertensive treatment, as well as true resistant hypertension (3). In the study by Verloop and coworkers, 2 out of every 3 patients referred for renal denervation because of apparent resistant hypertension did not have true resistant hypertension and therefore were not considered eligible for the procedure. Nonand poor adherence to prescribed treatment occurred frequently in this referral population, leading the authors to recommend careful screening of patients with apparent resistant hypertension before undertaking renal denervation procedures. The main aim of such a screening program is to confi rm the persistence of uncontrolled hypertension despite adequate medical treatment and to exclude secondary forms of hypertension. The Symplicity HTN-2 study (4) is the only randomized controlled trial of renal sympathetic denervation that has been reported to date. Symplicity HTN-2 randomized 106 patients with apparent treatment resistant hypertension to renal sympathetic denervation or control and followed them for 6 months. Offi ce BPs were reduced by 32/12 mmHg in the intervention group at 6 months and remained unchanged in the control group. Reductions in ambulatory BP were much smaller, suggesting, a “ white coat ” effect. Further, drug adherence was not thoroughly investigated (4). Poor drug adherence is a common problem among patients with apparent treatment resistant hypertension (5,6). For example, a recent study of 84 patients taking on average 5 antihypertensive drugs found no detectable blood levels of any antihypertensive drug in 34.5% of the patients, and that 65.5% of the patients fulfi lled the criteria of nonadherence (7). It is not known to what extent the reduction in BP that is observed following renal denervation is caused by the denervation per se or by increased drug adherence. It is reasonable to postulate that patients with poor drug adherence who undergo renal denervation receive so much positive attention at follow-up that they become more adherent to their antihypertensive medications and thus have enhanced BP reductions. Some patients may even discontinue their antihypertensive drugs prior to qualifi cation procedures for renal denervation and then resume their medication after the procedure. This could not be detected by the methods employed in Symplicity HTN-2 (4), and these defi ciencies provided the impetus for the more tightly controlled Symplicity HTN-3 study in the USA, which includes a sham operated control group (8). Drug adherence may be assessed in several ways, e.g. by electronic pill boxes, blood and urine measurements of prescribed drugs or by written patient ’ s diaries. However, measurement of drugs in blood or Blood Pressure, 2013; 22: 279–281

Risk of hospitalized gastrointestinal bleeding in persons randomized to diuretic, ACE-inhibitor, or calcium-channel blocker in ALLHAT.

Abstract: Calcium channel blockers (CCBs) are an important class of medication useful in the treatment of hypertension. Several observational studies have suggested an association between CCB therapy and gastrointestinal (GI) hemorrhage. Using administrative databases, the authors re-examined in a post-hoc analysis whether the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants randomized to the CCB amlodipine had a greater risk of hospitalized GI bleeding (a prespecified outcome) compared with those randomized to the diuretic chlorthalidone or the angiotensin-converting enzyme inhibitor lisinopril. Participants randomized to chlorthalidone did not have a reduced risk for GI bleeding hospitalizations compared with participants randomized to amlodipine (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.92-1.28). Those randomized to lisinopril were at increased risk of GI bleeding compared with those randomized to chlorthalidone (HR, 1.16; 95% CI, 1.00-1.36). In a post-hoc comparison, participants assigned to lisinopril therapy had a higher risk of hospitalized GI hemorrhage (HR, 1.27; 95% CI, 1.06-1.51) vs those assigned to amlodipine. In-study use of atenolol prior to first GI hemorrhage was related to a lower incidence of GI bleeding (HR, 0.69; 95% CI, 0.57-0.83). Hypertensive patients on amlodipine do not have an increased risk of GI bleeding hospitalizations compared with those taking either chlorthalidone or lisinopril.

The Human Side of Failed Hypertension Treatment

Abstract: Although hypertension is usually not associated with physical symptoms, there is survey evidence that many patients, perhaps the majority, see this condition as a cause for worry and a threat to their overall health. It is a reasonable assumption that these concerns are most manifest in patients whose blood pressures (BPs) are not well controlled. As well, there is evidence derived from psychological testing that people with hypertension experience reductions in quality of life that are proportional to their BP elevations. A recent study of attitudes in patients with selfdescribed uncontrolled or treatment-resistant hypertension by Schmieder and colleagues has established that these individuals carry a heavy emotional burden. The authors of this work reported the results of a survey conducted by the professional polling organization, Harris Interactive (New York). The survey questions had been designed in collaboration with a steering committee of hypertension experts (see Acknowledgements Section for details). The work of Harris Interactive and the committee was supported by an unrestricted grant from Medtronic. Overall, 4574 patients from the United States, Brazil, Japan, and several Western European countries with self-reported uncontrolled or treatment-resistant hypertension were surveyed. In response to the question: “How would you describe your current overall health?” more than half of the respondents chose “poor” or “fair” rather than “good” or “excellent.” In addition, they indicated a sense of pessimism about the probability of their BPs ever being controlled. All aspects of health appeared to be compromised by their hypertension, including a fear by many patients for their future well-being. Even personal and family relationships were found to be adversely affected.

Reply to Visit‐to‐Visit Blood Pressure Variation: Time to Reanalyze All The Data From the TROPHY Study

Abstract: To the Editor: We are glad to see that 6 years after publication of the Trial of Preventing Hypertension (TROPHY), the results are still being debated. Only truly new and important findings can elicit such an interest. TROPHY reported more robust results in the first 2 than in the second 2 years of the study. Two years of treatment with candesartan produced a 66.3% relative risk reduction (RRR) of hypertension, and the treatment was well tolerated. At the end of year 4, the RRR in the group that had been switched from candesartan to placebo at year 2 was highly significant but clinically modest (15.6%). We stated that “we do not advocate treatment of 25 million people with prehypertension and that further studies are needed.” This call for action was a smashing success. The Short Treatment with the Angiotensin Receptor Blocker Candesartan Surveyed by Telemedicine (STAR CAST) study in Japan will analyze the reversal from stage 1 to prehypertension and is nearly completed. The CHINON study in China recruited 10,000 patients and will compare cardiovascular outcomes in active treatment and placebo groups. In Brazil the Hypertension Prevention in Pre-Hypertensive Individuals (PREVER) study evaluates the effect of diuretic treatment in patients with prehypertension who failed to respond to lifestyle modification. In the meantime, we responded to an early critique of TROPHY by reanalyzing data according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) definition of hypertension. In the reanalysis, all original findings were confirmed and the median time to hypertension as defined by JNC 7 was 4.0 years in the group previously randomized to candesartan. Thus, according to current standards for initiation of treatment, 50% of patients did not need to resume medication up to 2 years after cessation of a 2year course of candesartan. We are disappointed that this body of work had escaped Dr Schalkwyk’s and Turner’s attention. We have recently published a paper in this Journal on the measurement of visit-to-visit variability of blood pressure (BP) using data from the placebo arm of the TROPHY trial. This work was intended to investigate different approaches to the estimation of visit-to-visit variability, an active area of BP research. The authors of the letter note that the BP visit-to-visit variability is higher in treated compared with the untreated patients, referring to the results in Figure 1 of the article. Their observation is what one would expect when BP is treated; that is, the visit-to-visit variability for patients initiating treatment for hypertension will be higher than those not initiating treatment because of the effect of treatment. For example, if a patient has systolic BP readings of 143, 139, 145, and 146 mmHg at visits 1 through 4 without antihypertensive medication use (pretreatment: standard deviation=3.1 mm Hg) and 134, 128, 135, and 132 mm Hg at visits 5 through 8 following antihypertensive medication initiation (posttreatment: standard deviation=3.1 mm Hg), the overall standard deviation will be 6.5 mm Hg, which more than doubles from the actual value due to treatment effect. When the effect of treatment is excluded, that is, the post-treatment BP measures were censored, the variability in patients who initiated treatment vs patients always untreated was similar (Figure 1). TROPHY produced a rich set of data that we will continue to analyze according to our sense of priorities. We anticipate that ongoing trials will clarify many questions that TROPHY could not resolve. However, there is a need for additional studies. None of the ongoing trials of prehypertension will discontinue active treatment and thereafter evaluate incident hypertension. We invite Drs Schalkwyk and Turner to join the international community and design an AustralianNew Zealand study that could provide new insights and verify or disprove their assumptions.

Revisiting the pre-hypertension debate: Increasing evidence for treatment – or not?

Abstract: The editors of Blood Pressure , although accepting the paper by Reed et al. (1) for publication inasmuch as it is nicely reviewing many studies showing high cardiovascular risk associated with pre-hypertension and high normal blood pressure, would like to extend the reservation expressed by Gordon T. McInnes in his letter response to the editors. We herewith in the paragraph below repeat the abstract written by Gordon T. McInnes in 2009 (3).

Primary cardiovascular prevention by Mediterranean diet – The PREDIMED trial

Abstract: Traditionally, the Mediterranean diet is composed of olive oil, fruit, nuts, vegetables, and cereals. Fish and poultry intake is moderate and consumption of dairy products, red meat, processed meat...

Novel strategies for treatment of resistant

Abstract: Despite the availability of a large variety of pharmacologic agents that, alone and in combination, are highly effective in lowering blood pressure (BP), 410% of hypertensive patients cannot be controlled with drug treatment and lifestyle modification alone. 1 Resistant hypertension, defined as BP remaining above goal despite the use of three or more antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires four or more agents to achieve control, occurs in approximately 13% of treated hypertensive patients in the United States. 1,2 Further, patients with refractory hypertension, a subset of those with resistant hypertension, have BP that cannot be controlled with maximal medical therapy (X5 antihypertensive medications of different classes at maximal tolerated doses). 3 Refractory hypertension accounts for 2‐3% of all treated hypertensives and 6% of resistant hypertensives. 3 As patients with resistant hypertension and, in particular, those with refractory hypertension, are at greatly increased cardiovascular disease (CVD) risk, they are in urgent need of novel approaches for BP lowering.