Masked hypertension: understanding its complexity.

Masked hypertension, which is present when in-office normotension translates to out-of-office hypertension, is present in a surprisingly high percentage of untreated persons and an even higher percentage of patients after beginning antihypertensive medication. Not only are persons with prehypertension more likely to have masked hypertension than those with optimal blood pressure (BP), but also they frequently develop target organ damage prior to transitioning to sustained hypertension. Furthermore, the frequency of masked hypertension is high in individuals of African inheritance and in the presence of increased cardiovascular risk factors and disease states, such as diabetes and chronic renal failure. Nocturnal hypertension and non-dipping may be early markers of masked hypertension. Twenty-four hour ambulatory BP monitoring (ABPM), which can detect nighttime and 24 h elevated BP, remains the gold standard for diagnosing masked hypertension. Almost one-third of treated patients with masked hypertension remain as 'masked uncontrolled hypertension', and it becomes important, therefore, to use ABPM (and supplemental home BP monitoring) for the effective diagnosis and control of hypertension.

Central blood pressure: current evidence and clinical importance.

Pressure measured with a cuff and sphygmomanometer in the brachial artery is accepted as an important predictor of future cardiovascular risk. However, systolic pressure varies throughout the arterial tree, such that aortic (central) systolic pressure is actually lower than corresponding brachial values, although this difference is highly variable between individuals. Emerging evidence now suggests that central pressure is better related to future cardiovascular events than is brachial pressure. Moreover, anti-hypertensive drugs can exert differential effects on brachial and central pressure. Therefore, basing treatment decisions on central, rather than brachial pressure, is likely to have important implications for the future diagnosis and management of hypertension. Such a paradigm shift will, however, require further, direct evidence that selectively targeting central pressure, brings added benefit, over and above that already provided by brachial artery pressure.

The complexity of masked hypertension: diagnostic and management challenges.

Masked hypertension, defined as discordant in-office normotension versus out-of-office hypertension, is present in approximately 10 % to 40 % of patients not receiving antihypertensive treatment. Not only are persons with prehypertension more likely to have masked hypertension, but they also frequently develop target organ damage before transitioning to established sustained hypertension. Moreover, the percentage of persons with masked hypertension increases in the presence of cardiovascular disease, diabetes, or chronic renal failure. The gold standard for diagnosing masked hypertension is the 24-hour ambulatory BP monitor (ABPM), but home BP monitoring (HBPM) has also been a useful alternative procedure. Importantly, initiating antihypertensive treatment exclusively with the use of in-office BP monitoring may result in almost one-third of patients remaining with high-risk masked uncontrolled hypertension, which underscores the importance of HBPM and ABPM as supplements to in-office BP monitoring for the effective treatment of hypertension.

Blood pressure and pulse wave velocity as metrics for evaluating pathologic ageing of the cardiovascular system.

The influence of chronological ageing on the components of the cardiovascular system is of fundamental importance for understanding how hemodynamics change and the cardiovascular risk increases with age, the most important risk marker. An increase in peripheral vascular resistance associated with increased stiffness of central elastic arteries represents hallmarks of this ageing effect on the vasculature, referred to as early vascular ageing (EVA). In clinical practice, it translates into increased brachial and central systolic blood pressure and corresponding pulse pressure in subjects above 50 years of age, as well as increased carotid-femoral pulse wave velocity (c-f PWV)--a marker of arterial stiffness. A c-f PWV value ≥ 10 m/s is threshold for increased risk according. Improved lifestyle and control of risk factors via appropriate drug therapy are of importance in providing vascular protection related to EVA. One target group might be members of risk families including subjects with early onset cardiovascular disease.

How much effect of different antihypertensive medications on cardiovascular outcomes is attributable to their effects on blood pressure?

The debate over whether certain antihypertensive medications have benefits beyond what would be expected from their blood pressure lowering spurred the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, which randomized 42,418 participants to chlorthalidone (15,255), amlodipine (9048), lisinopril (9054), or doxazosin (9061). We compared chlorthalidone, the active control, with each of the other three agents with respect to the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, and several other clinical endpoints. The arms were similar with respect to the primary endpoint, although some differences were found for other endpoints, most notably heart failure. Although the desire was to achieve similar blood pressure reductions in the four arms, we found some systolic blood pressure and diastolic blood pressure differences. A natural question is to what degree can observed treatment group differences in cardiovascular outcomes be attributed to these blood pressure differences. The purpose of this paper was to delineate the problems inherent in attempting to answer this question, and to present analyses intended to overcome these problems.

Single versus combined blood pressure components and risk for cardiovascular disease: the Framingham Heart Study.

BACKGROUND: The utility of single versus combined blood pressure (BP) components in predicting cardiovascular disease (CVD) events is not established. We compared systolic BP (SBP) and diastolic BP (DBP) versus pulse pressure (PP) and mean arterial pressure (MAP) combined and each of these 4 BP components alone in predicting CVD events. METHODS AND RESULTS: In participants in the original (n=4760) and offspring (n=4897) Framingham Heart Study who were free of CVD events and BP-lowering therapy, 1439 CVD events occurred over serial 4-year intervals from 1952 to 2001. In pooled logistic regression with the use of BP categories, combining SBP with DBP and PP with MAP improved model fit compared with individual BP components (P<0.05 to P<0.0001). Significant interactions were noted between SBP and DBP (P=0.02) and between PP and MAP (P=0.01) in their respective multivariable models. Models with continuous variables for SBP+DBP and PP+MAP proved identical in predicting CVD events (Akaike Information Criteria=10 625 for both). Addition of a quadratic DBP(2) term to DBP and SBP further improved fit (P=0.0016). CONCLUSIONS: Combining PP with MAP and SBP with DBP produced models that were superior to single BP components for predicting CVD, and the extent of CVD risk varied with the level of each BP component. The combination of PP+MAP (unlike SBP+DBP) has a monotonic relation with risk and may provide greater insight into hemodynamics of altered arterial stiffness versus impaired peripheral resistance but is not superior to SBP+DBP in predicting CVD events.

Pulse pressure and risk of cardiovascular outcomes in patients with hypertension and coronary artery disease: an INternational VErapamil SR-trandolapril STudy (INVEST) analysis.

AIM: The purpose of this study was to assess the relationship between pulse pressure (PP) and cardiovascular outcomes in a large, elderly, coronary artery disease (CAD) population with hypertension, and compare the predictive power of PP with other blood pressure measures. METHODS AND RESULTS: In INternational VErapamil-trandolapril STudy, 22,576 CAD patients with hypertension (mean age 66 years) were randomized to verapamil-SR or atenolol-based strategies and followed for 2.7 years (mean). Primary outcome (PO) was time to first occurrence of death (all-cause), non-fatal myocardial infarction (MI), or non-fatal stroke. Mean follow-up PP was summarized by 5 mmHg subgroups for association with incidence of PO. Stepwise Cox proportional hazards models were used to estimate adjusted relative hazard ratios (HR) for the risk of PO with follow-up PP as a continuous variable, with linear and quadratic terms. Similar models were constructed for follow-up systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP). A -2 log-likelihood statistic was used to assess the predictive power of PP compared with SBP, DBP, and MAP. For follow-up PP, the incidence and adjusted HR for the PO formed a J- or U-shaped curve. After adjusting for baseline covariates, both linear and quadratic terms for PP were significant (P < 0.0001 for both), with a nadir of 54 mmHg (bootstrapping 95% CI 42-60 mmHg). Similar quadratic relationships were found between PP and all-cause mortality or MI; the relationship between PP and stroke was linear. Pulse pressure was a predictor of PO even after including SBP (P = 0.007 linear term) or DBP (P < 0.0001 for both linear and quadratic terms) or MAP (P < 0.01 for both liner and quadratic terms) in the model. Using -2 log-likelihood differences, SBP (-2 log-likelihood difference 77.1 vs. 7.3 for PP), DBP (-2 log-likelihood difference 138.5 vs. 44.6 for PP), and MAP (-2 log-likelihood difference 125.0 vs. 13.4 for PP) were stronger predictors of PO than PP. CONCLUSION: In CAD patients with hypertension, PP (on anti-hypertensive treatment) is a weaker predictor of cardiovascular outcomes than SBP, DBP, or MAP.

Pulse pressure, left ventricular function and cardiovascular events during antihypertensive treatment (the LIFE study).

BACKGROUND: Pulse pressure (PP) has been related to risk of cardiovascular events in hypertension. However, less is known about modification of this risk marker during antihypertensive treatment in patients with left ventricular (LV) hypertrophy. METHODS: Associations of in-treatment PP with LV systolic function and cardiovascular events was assessed in 883 patients with electrocardiographic LV hypertrophy during 4.8 years of randomized losartan- or atenolol-based treatment within the echocardiographic substudy of the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. RESULTS: PP was similarly reduced by both treatments. In different multiple regression models, lower in-treatment PP was independently associated with lower in-treatment LV ejection fraction (beta=0.16), stress-corrected midwall shortening (beta=0.20), stroke volume (beta=0.11) and cardiac index (beta=0.07, all p<0.05). In time-varying Cox regression models, 10 mmHg lower in-treatment PP was associated with a 28% higher rate of cardiovascular events [hazard ratio, HR = 1.28 (1.09 - 1.52), p<0.01] independent of in-treatment LV mass and ejection fraction, history of ischemic heart disease, Framingham risk score and study treatment allocation. CONCLUSION: During systematic antihypertensive treatment in hypertensive patients with electrocardiographic LV hypertrophy, lower in-treatment PP was associated with lower in-treatment LV function and cardiac output as well as higher rate of cardiovascular events.

Safety and tolerability of fixed-dose irbesartan/hydrochlorothiazide for rapid control of severe hypertension.

This prospective, double-blind, multicenter trial compared the safety and tolerability of irbesartan/hydrochlorothiazide (HCTZ) fixed-dose combination therapy with irbesartan monotherapy in patients with severe hypertension (seated diastolic blood pressure (SeDBP) >or=110 mm Hg, mean BP 172/113 mm Hg at baseline). Patients were randomized 2:1 to 7 weeks' irbesartan/HCTZ 150/12.5 mg to 300/25 mg (n = 468) or irbesartan 150 mg to 300 mg (n = 227). The incidence of treatment-related adverse events (AEs) was similar with combination and monotherapy (11.3% and 10.1%), and most AEs were mild-to-moderate. The combined incidence of prespecified AEs was lower with irbesartan/HCTZ than with irbesartan (8.8% vs. 11.5%). There were no treatment-related serious AEs or deaths. At week 5, more patients achieved SeDBP < 90 mm Hg compared to irbesartan (47% vs. 33%; P = 0.0005). Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesartan monotherapy in patients with severe hypertension.

Superiority of Out-of-Office Blood Pressure for Predicting Hypertensive Heart Disease in Non-Hispanic Black Adults.

Black Americans suffer disproportionately from hypertension and hypertensive heart disease. Out-of-office blood pressure (BP) is more predictive for cardiovascular complications than clinic BP; however, the relative abilities of clinic and out-of-office BP to predict left ventricular hypertrophy in black and white adults have not been established. Thus, we aimed to compare associations of out-of-office and clinic BP measurement with left ventricular hypertrophy by cardiac magnetic resonance imaging among non-Hispanic black and white adults. In this cross-sectional study, 1262 black and 927 white participants of the Dallas Heart Study ages 30 to 64 years underwent assessment of standardized clinic and out-of-office (research staff-obtained) BP and left ventricular mass index. In multivariable-adjusted analyses of treated and untreated participants, out-of-office BP was a stronger determinant of left ventricular hypertrophy than clinic BP (odds ratio per 10 mm Hg, 1.48; 95% CI, 1.34-1.64 for out-of-office systolic BP and 1.15 [1.04-1.28] for clinic systolic BP; 1.71 [1.43-2.05] for out-of-office diastolic BP, and 1.03 [0.86-1.24] for clinic diastolic BP). Non-Hispanic black race/ethnicity, treatment status, and lower left ventricular ejection fraction were also independent determinants of hypertrophy. Among treated Blacks, the differential association between out-of-office and clinic BP with hypertrophy was more pronounced than in treated white or untreated participants. In conclusion, protocol-driven supervised out-of-office BP monitoring provides important information that cannot be gleaned from clinic BP assessment alone. Our results underscore the importance of hypertension management programs outside the medical office to prevent hypertensive heart disease, especially in high-risk black adults. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00344903.

Inadequate control of hypertension in US adults with cardiovascular disease comorbidities in 2003-2004.

BACKGROUND: Cardiovascular risks associated with hypertension (HTN) and the importance of its control are well established; however, the prevalence and adequacy of its treatment and control in persons with cardiovascular comorbidities (CVCs) are uncertain. METHODS: To examine the prevalence, treatment, and control of HTN among US adults with and without CVCs, we analyzed data from adults at least 18 years of age (n = 4646, N [projected sample size] = 192.4 million) in the National Health and Nutrition Examination Survey 2003-2004, a nationally representative cross-sectional survey of the noninstitutionalized civilian US population. Prevalence, treatment, and control rates of HTN in patients with CVCs vs those without, including coronary artery disease, congestive heart failure, stroke, chronic kidney disease, peripheral artery disease, and diabetes mellitus, and distance to blood pressure goal in those whose HTN was not controlled were the main outcomes. RESULTS: The overall prevalence rate of HTN was 31.4% (n = 1671, N = 60.5 million), ranging from 23.1% in those without CVCs to 51.8% to 81.8% in those with CVCs (P < .01). Despite HTN treatment rates for diabetes mellitus, stroke, heart failure, and coronary artery disease that are higher (83.4%-89.3%) than the rates of those without these conditions (66.5%) (P < .01), control rates for treatment remained poor (23.2%-49.3%) (P < .001 to P = .048). Isolated systolic HTN was the most common hypertensive subtype in those with CVCs (> or = 63.5%) with systolic blood pressure averaging at least 20 mm Hg from goal. CONCLUSIONS: Nearly three-fourths of adults with CVCs have HTN. Poor control rates of systolic HTN remain a principal problem that further compromises their already high cardiovascular disease risk.

Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

BACKGROUND: Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. METHODS AND RESULTS: ALLHAT was a double-blind, randomized, clinical trial in 33,357 high-risk hypertensive patients aged > or =55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. CONCLUSIONS: HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.

Hypertension management: results of a new national survey for the hypertension education foundation: Harris interactive.

A new national online survey by Harris Interactive of 1245 hypertensive individuals indicates that >90% were aware that elevated blood pressure (BP) is a major risk factor for cardiovascular disease. The majority discovered that they had elevated BP levels as a result of a routine examination. More than two thirds of persons identified 120/80 mm Hg as an optimal BP level; only 6.0% stated that the Internet was their primary source of information about high BP. More than 60% of respondents had a body mass index >30 kg/m(2), and >50% had other cardiovascular risk factors. More than 50% were involved in some lifestyle change to control BP, and >90% were taking medication. More than 60% reported that BP was controlled (<140/90 mm Hg) at the last visit, although approximately 50% were told that their BP was high at some time. The survey results suggest that >90% of hypertensive patients are aware of the risks of elevated BP and that a high percentage of hypertensive patients are being treated with medication. Control rates as reported by respondents were >60% based on last BP recorded; however, between 31% and 40% of patients (based on differences in ethnic groups) were continued on the same therapy despite elevated BP levels. The survey suggests a high degree of risk awareness and treatment, and what appears to be an increase in control rates among hypertensive patients.

The nonpharmacologic treatment of hypertension: how effective is it? An update.

Following a hypertension symposium in Los Angeles, CA, in October 2006, a panel was convened to update information about lifestyle changes or the nonpharmacologic treatment of hypertension. Dr Marvin Moser, Clinical Professor of Medicine at the Yale University School of Medicine, moderated the panel. Dr Stanley S. Franklin, Clinical Professor of Medicine and Associate Medical Director of the Heart Disease Prevention Program at the University of California, Irvine, and Dr Joel Handler, Director of the Orange County Kaiser-Permanente Hypertension Clinic and clinical hypertension leader of the Care Management Institute of Kaiser Permanente, participated in the discussion.

Initial combination therapy with irbesartan/hydrochlorothiazide for hypertension: an analysis of the relationship between baseline blood pressure and the need for combination therapy.

Hypertension treatment guidelines recommend initiating 2-drug therapy whenever blood pressure (BP) is > or =20 mm Hg systolic or > or =10 mm Hg diastolic above goal. This post hoc pooled analysis of 2 multicenter, randomized, double-blind, active-controlled forced-titration studies in 1235 patients with moderate and severe hypertension examined how baseline BP levels relate to the need for combination therapy by comparing the antihypertensive efficacy and tolerability of once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg compared with irbesartan 300-mg or HCTZ 25-mg monotherapies. In study 1, patients with severe hypertension (seated diastolic BP [SeDBP] > or =110 mm Hg) were treated for 7 weeks with irbesartan or irbesartan/HCTZ combination therapy, with forced-titration after week 1. In study 2, patients with moderate hypertension (seated systolic BP [SeSBP] 160-180 mm Hg or SeDBP 100-110 mm Hg) were treated for 12 weeks with irbesartan/HCTZ, irbesartan monotherapy, or HCTZ monotherapy, with forced-titration after week 2. The relationship between baseline BP and the likelihood of achieving BP goals (SeSBP <140 mm Hg or SeDBP <90 mm Hg; SeSBP <130 mm Hg or SeDBP <80 mm Hg) as well as the antihypertensive response was evaluated at week 7/8. The need for combination therapy increased with increasing baseline BP and lower BP goals across the range of BP levels studied, with a comparable adverse effect profile to monotherapy. These results suggest that the likelihood of achieving an early BP goal for a given BP severity should be considered when choosing initial combination therapy vs monotherapy.

Hypertension control: still not there-how to select the right add-on therapy to reach goal blood pressures.

This expert panel discussion was held on August 17, 2007. The panel was moderated by Joel M. Neutel, MD, Orange County Research Center, Tustin, California. Participants included Domenic A. Sica, MD, Virginia Commonwealth University, Richmond, Virginia, and Stanley S. Franklin, MD, University of California, Irvine, Irvine, California. The discussion was supported by Boehringer Ingelheim, and each author received an honorarium from Boehringer Ingelheim for time and effort spent participating in the discussion and reviewing the transcript for intellectual content before publication. The authors maintained full control of the discussion and the resulting content of this article.

Coronary heart disease events preventable by control of blood pressure and lipids in US adults with hypertension.

Hypertension (HTN) and dyslipidemia are major risk factors for coronary heart disease (CHD). In 676 (projected to 26.1 million) US persons from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 with HTN, the authors estimated the preventable CHD events from statistical control of blood pressure (BP) and lipid levels. Using Framingham algorithms, the authors projected the CHD events that could be prevented from statistical control of BP, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. If BP was controlled to nominal levels, the authors projected 19% of CHD events (37% if controlled to optimal) would be prevented. Improving lipid levels to nominal levels was estimated to prevent 27% of CHD events (62% if controlled to optimal). Combined control of BP and lipid levels to nominal levels was projected to prevent 38% of CHD events (76% if controlled to optimal). The authors' results demonstrate that combined control of BP and lipid levels may prevent the majority of CHD events in Americans with HTN.

Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate.

BACKGROUND: Chronic kidney disease is common in older patients with hypertension. OBJECTIVE: To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR. DESIGN: Post hoc subgroup analysis. SETTING: Multicenter randomized, double-blind, controlled trial. PARTICIPANTS: Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m2; n = 5662 patients). INTERVENTIONS: Random assignment to chlorthalidone, amlodipine, or lisinopril. MEASUREMENTS: Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease). RESULTS: In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure. LIMITATIONS: Proteinuria data were not available, and combination therapies were not tested. CONCLUSIONS: Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.