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.

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.

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.

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.

Expertise: no longer a sine qua non for guideline authors?

: Several sets of guidelines have been published recently and more are in the works. The very recent American College of Physicians/American Academy of Family Practitioners guidelines were put together by a set of authors and consultants without any expertise in the topic under discussion, that is, hypertension. Although we are not maintaining that all guidelines should be written exclusively by experts, complete lack of expertise among guideline authors is not acceptable.

Predictors of new-onset diastolic and systolic hypertension: the Framingham Heart Study.

BACKGROUND: Factors leading differentially to the development of isolated diastolic (IDH), systolic-diastolic (SDH), and isolated systolic (ISH) hypertension are poorly understood. We examined the relations of blood pressure (BP) and clinical risk factors to the new onset of the 3 forms of hypertension. METHODS AND RESULTS: Participants in the Framingham Heart Study were included if they had undergone 2 biennial examinations between 1953 and 1957 and were free of antihypertensive therapy and cardiovascular disease. Compared with optimal BP (SBP <120 and DBP <80 mm Hg), the adjusted hazard ratios (HRs) for developing new-onset IDH over the ensuing 10 years were 2.75 for normal BP, 3.29 for high-normal BP (both P<0.0001), 1.31 (P=0.40) for SDH, and 0.61 (P=0.36) for ISH. The HRs of developing new-onset SDH were 3.32, 7.96, 7.10, and 23.12 for the normal BP, high-normal BP, ISH, and IDH groups, respectively (all P<0.0001). The HRs of developing ISH were 3.26 for normal and 4.82 for high-normal BP (both P<0.0001), 1.39 (P=0.24) for IDH, and 1.69 (P<0.01) for SDH. Increased body mass index (BMI) during follow-up predicted new-onset IDH and SDH. Other predictors of IDH were younger age, male sex, and BMI at baseline. Predictors of ISH included older age, female sex, and increased BMI during follow-up. CONCLUSIONS: Given the propensity for increased baseline BMI and weight gain to predict new-onset IDH and the high probability of IDH to transition to SDH, it is likely that IDH is not a benign condition. ISH arises more commonly from normal and high-normal BP than from "burned-out" diastolic hypertension.

Blood pressure categories, hypertensive subtypes, and the metabolic syndrome.

BACKGROUND: Elevated blood pressure (BP) is one element of metabolic syndrome (MetS); however, the relation of various BP categories and hypertension subtypes to the likelihood of having MetS is not well defined. METHODS: We determined the odds of MetS, defined by the National Cholesterol Education Program, in various BP categories from a cross-sectional study of 5968 individuals aged at least 18 years and untreated for hypertension (weighted to 124.7 million) in the National Health and Nutrition Examination Survey, 1999-2002. Nonhypertensive BP categories were optimal, normal, and high-normal BP, according to JNC-VI classification. Hypertension consisted of three subtypes: isolated diastolic hypertension (IDH), systolic-diastolic hypertension (SDH), and isolated systolic hypertension (ISH). RESULTS: Among those with hypertension and MetS, 25.3% had IDH, 20.2% had SDH, and 54.5% had ISH. The MetS prevalence in nontreated persons was 5.8% for optimal BP, 9.1% for normal BP, 38.2% for high-normal BP, 45.9% for IDH, 44.3% for SDH, and 43.9% for ISH. Risk factor odds ratios (95% confidence intervals; reference group, optimal BP), adjusted for age, sex, total cholesterol, and smoking, were 1.6 (1.2-2.2) for normal BP, 9.4 (6.9-12.7) for high-normal BP, 14.7 (8.9-24.0) for IDH, 12.2 (7.2-20.8) for SDH, and 10.2 (7.0-14.9) for ISH (all P < 0.01); odds ratios were higher for women in all categories. CONCLUSIONS: Despite having the lowest mean age, IDH subtype is associated with greatest likelihood of MetS. The high frequency of ISH in the hypertensive population, however, makes ISH the most common hypertensive subtype in persons with MetS.

Hypertension in older people: part 1.

Once considered part of the normal aging process, the development of isolated systolic hypertension represents a late manifestation of increased arterial stiffness in older people. Furthermore, isolated systolic hypertension is the single most frequent subtype of hypertension in the US adult population. Indeed, central arterial stiffness rather than peripheral vascular resistance becomes the dominant hemodynamic factor in both normotensive and hypertensive individuals after the age of 50-60 years. Stiffening disease, an age-related degeneration of the elastic elements of the thoracic aorta, is associated with a widening of brachial pulse pressure. Brachial pulse pressure predicts future cardiovascular disease events. However, pressure wave amplification produces higher brachial than aortic pressures and, therefore, central rather than peripheral blood pressure indices are more reliable measures of cardiovascular risk. Stiffening disease of aging is accompanied by early wave reflection, which results in a significant augmentation of central systolic pressure in late systole and further adds to increased cardiac afterload--so-called ventricular-vascular uncoupling. Diabetes, impaired renal function, and untreated or poorly treated hypertension may lead to premature arterial stiffening; its consequences are stiffening and hypertrophy of the left ventricle and predisposition to coronary heart disease, heart failure, stroke, vascular dementia, and chronic kidney disease.