Stanley Franklin | University of California, Irvine (original) (raw)
Papers by Stanley Franklin
The 2014 Eighth Joint National Committee panel recommends a therapeutic target of systolic blood ... more The 2014 Eighth Joint National Committee panel recommends a therapeutic target of systolic blood pressure (BP) <150 mm Hg in patients ≥60 years of age, a departure from prior recommendation of <140 mm Hg.
Hypertension, 2012
The significance of white-coat hypertension in older persons with isolated systolic hypertension ... more The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular
Based on individual patient data, we performed a quantitative overview of trials in hypertension ... more Based on individual patient data, we performed a quantitative overview of trials in hypertension to investigate to what extent lowering of systolic blood pressure (SBP) and diastolic blood pressure (DBP) contributed to cardiovascular prevention. We selected trials that tested active antihypertensive drugs against placebo or no treatment. Our analyses included 12 903 young (30 to 49 years of age) patients
American journal of hypertension, 2004
Once considered an inconsequential part of the aging process, an age-associated rise in systolic ... more Once considered an inconsequential part of the aging process, an age-associated rise in systolic blood pressure (SBP) occurs as a consequence of increased arterial stiffness and contributes to a high prevalence of systolic hypertension after middle-age. Elevated SBP imparts a predilection toward the onset of vascular events, highlighting the importance of its control. Current philosophy ranks systolic pressure as the most relevant component of blood pressure (BP) for determining risk for cardiovascular and other events in hypertensive patients, particularly those >50 years of age. Despite its prognostic role, SBP remains more difficult to control than diastolic BP (DBP), and most middle-age and older hypertensive patients fail to achieve recommended targets. In part, the lack of strict control of SBP in the more aged population lies in the physiology of hypertension. Younger persons tend toward isolated diastolic hypertension or combined systolic-diastolic hypertension, primarily...
Journal of the American Society of Hypertension, 2014
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a ra... more The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, doubleblind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 ¼ 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 ¼ 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). Intrial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P ¼ .005, race-by-amlodipine/lisinopril interaction P ¼ .012) and gender (gender-by-lisinopril/amlodipine interaction P ¼ .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period. J Am Soc Hypertens 2014;8(11):808-819.
6 treatment goal of less than 140/90 mmHg, and to less than 130/85 mmHg in those at highest risk,... more 6 treatment goal of less than 140/90 mmHg, and to less than 130/85 mmHg in those at highest risk, especially patients with significant kidney disease or diabetes. We must recommit ourselves to educate, motivate, and treat our patients until they reach the treatment goal that may extend their lives. High blood pressure is endemic in this country. It is our
Journal of the American College of Cardiology, Jan 3, 2015
Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mm Hg and dia... more Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg, in younger and middle-aged adults is increasing in prevalence. The aim of this study was to assess the risk for cardiovascular disease (CVD) with ISH in younger and middle-aged adults. CVD risks were explored in 15,868 men and 11,213 women 18 to 49 years of age (mean age 34 years) at baseline, 85% non-Hispanic white, free of coronary heart disease (CHD) and antihypertensive therapy, from the Chicago Heart Association Detection Project in Industry study. Participant classifications were as follows: 1) optimal-normal blood pressure (BP) (SBP <130 mm Hg and DBP <85 mm Hg); 2) high-normal BP (130 to 139/85 to 89 mm Hg); 3) ISH; 4) isolated diastolic hypertension (SBP <140 mm Hg and DBP ≥90 mm Hg); and 5) systolic diastolic hypertension (SBP ≥140 mm Hg and DBP ≥90 mm Hg). During a 31-year average follow-up period (842,600 person-years), there...
Background—Current definitions of hypertension are based on levels of systolic blood pressure (SB... more Background—Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study. Methods and Results—We studied 1924 men and women between 50 and 79 years of age at baseline
Pulse pressure rather than diastolic pressure is the best predictor of coronary heart disease ris... more Pulse pressure rather than diastolic pressure is the best predictor of coronary heart disease risk in older subjects, but the converse is true in younger subjects. We hypothesized that this disparity results from an age-related difference in pressure amplification from the aorta to brachial artery. Data from 212 subjects age 50 years and 230 subjects age 50 years were abstracted
Kidney International, 1975
Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration... more Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration in 30 hemodialysis patients correlated closely with renin concentration, renin activity or renin and potassium concentrations combined (r is greater than or equal to 0.62; P is less than 0.01), and increased consistently in response to upright posture or corticotropin administration. Aldosterone response to hemodialysis was variable. Significant correlations (r is greater than or equal to 0.65; P is less than 0.01) were demonstrated between postural plasma aldosterone and renin responses, between aldosterone responses to corticotropin and basal plasma aldosterone or renin and potassium values, between hemodialysis-induced changes in plasma aldosterone and those in potassium or renin; but not between various indexes of heparin treatment and aldosterone activity. Bilateral nephrectomy reduced basal plasma renin and aldosterone concentrations and aldosterone responsiveness in five preoperatively normoreninemic or hyperreninemic patients, but not in a hyporeninemic patient. These results demonstrate the complementary roles of circulating renin and potassium in the control of aldosterone release under basal and stimulatory conditions in patients with terminal renal failure. Administration of heparin in dosages used during long-term hemodialysis does not appear to significantly interfere with aldosterone control.
Journal of the American Society of Hypertension, 2007
Brachial systolic blood pressure (SBP) is the overall best predictor of future cardiovascular ris... more Brachial systolic blood pressure (SBP) is the overall best predictor of future cardiovascular risk for the entire hypertensive population; however, there is much that can be learned from assessing diastolic blood pressure (DBP) in relation to simultaneous levels of SBP, because the former is not distorted by pressure amplification. Low DBP in very young adults (mean age 20 years), presenting as isolated systolic hypertension (ISH), results from elevation in stroke volume and/or arterial stiffness. This subtype of hypertension has a marked male predominance, occurs twice as frequently as essential hypertension, and is potentially not a benign condition. In contrast, isolated diastolic hypertension (IDH) in young adults (mean age of 40 years) with IDH occurs predominantly in men with a high prevalence of metabolic syndrome. Indeed, persons with IDH frequently evolve into systolic-diastolic hypertension and are potentially at increased risk for future diabetes and cardiovascular complications. The older age population with ISH and low DBP (mean age Ն60 years of age) has a high prevalence of left ventricular hypertrophy, increased ventricular-arterial stiffness, and a tendency for diastolic dysfunction and heart failure. Finally, concordant very high DBP, especially in older persons, defines potential hypertensive urgencies, emergencies, secondary forms of hypertension, and other high peripheral resistance states.
Journal of the American Society of Hypertension, 2008
Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular... more Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular aging, as well as a new biomarker of cardiovascular (CV) disease. Arterial stiffness also plays an important role in the development of isolated systolic hypertension (ISH) in the middle-aged and elderly population. ISH is characterized by an increase in pulse pressure (PP) in association with a rise in systolic blood pressure (SBP) and a fall in diastolic blood pressure (DBP). Increased PP, however, is not always a good surrogate for arterial stiffening because of the frequent discrepancy between peripheral brachial and central aortic PP values due to varying pressure amplification. Therefore, noninvasive, easily performed methods for more direct measurement of arterial stiffness and wave reflection, such as aortic pulse wave velocity (PWV) and pulse wave analysis, have been developed for clinical use. The present review aims to provide an understanding of the pathophysiology of arterial stiffness and wave reflection, to review the various techniques for their measurement, and to explore their usefulness in predicting CV risk and therapeutic benefit in comparison with traditional brachial artery cuff blood pressure (BP) by sphygmomanometry.
Journal of the American College of Cardiology, 2004
In patients with daytime hypertension (HT), Obstructive sleep apnea (OSA) is very often associate... more In patients with daytime hypertension (HT), Obstructive sleep apnea (OSA) is very often associated. The relationship between OSA and daytime HT could be due to many confounding factors such as age, gender, obesity, and race. However, exact mechanism by which OSA can lead to daytime HT is still unclear.
Journal of Human Hypertension, 2004
An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pre... more An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pressure is a more sensitive measure of risk than other indexes of blood pressure in middle-aged and older persons. The objective of the study was to relate pulse pressure to the risk of cardiovascular events in the general population, and to assess whether pulse pressure could improve the Framingham risk prediction. A total of 378 men and 391 women over the age of 50 years (mean 62.7 years) were followed. Sex-specific Framingham cardiovascular risk scores were derived from age, systolic pressure, diastolic pressure, total and HDL cholesterol, smoking status and the presence or absence of diabetes mellitus. The cutoff points used to develop a pulse pressure score were calculated by determining the percentile points corresponding to the blood pressure categories in the Framingham risk score. We calculated relative hazard rates by multiple Cox regression. After a median follow-up of 7.2 years (range: 11 months-15 years), a total of 148 cardiovascular events occurred. In Cox regression analysis, a 10 mmHg higher pulse pressure was associated with 31% (Po0.0001) increase in the risk for cardiovascular events (fatal and nonfatal) after adjustment for sex, age, total and HDL cholesterol, smoking and the presence of diabetes mellitus. After adjustment for the aforementioned risk factors, a onepoint increment in the blood pressure and pulse pressure scores was associated with a 40 and 48% (both Po0.0001) increase in the risk of fatal and nonfatal cardiovascular events, respectively. When both the blood pressure and pulse pressure scores were forced into a Cox model, only the pulse pressure score remained statistically significant (Po0.0001) with a relative hazard rate of 1.37 (CI: 1.16-1.69). These prospective data suggest that pulse pressure may improve the Framingham risk prediction among middle-aged and older individuals. Further studies, especially in the Framingham cohort, are warranted.
The Journal of Clinical Hypertension, 2007
Hypertension treatment guidelines recommend initiating 2-drug therapy whenever blood pressure (BP... more Hypertension treatment guidelines recommend initiating 2-drug therapy whenever blood pressure (BP) is &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =20 mm Hg systolic or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;140 mm Hg or SeDBP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;90 mm Hg; SeSBP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;130 mm Hg or SeDBP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.
The Journal of Clinical Hypertension, 2007
). In 676 (projected to 26.1 million) US persons from the National Health and Nutrition Examinati... more ). 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, lowdensity 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. (J Clin Hypertens. 2007;9:436-443)
Hypertension, 2012
The significance of white-coat hypertension in older persons with isolated systolic hypertension ... more The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular
Hypertension, 2013
Although distinguishing features of masked hypertension in diabetics are well known, the signific... more Although distinguishing features of masked hypertension in diabetics are well known, the significance of antihypertensive treatment on clinical practice decisions has not been fully explored. We analyzed 9691 subjects from the population-based 11-country International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes. Prevalence of masked hypertension in untreated normotensive participants was higher (P<0.0001) among 229
Hypertension, 2005
Isolated systolic hypertension is a common condition in individuals aged older than 60 years. How... more Isolated systolic hypertension is a common condition in individuals aged older than 60 years. However, isolated systolic hypertension has also been described in young individuals, although the mechanisms are poorly understood. We hypothesized that in young adults, isolated systolic hypertension and essential hypertension have different hemodynamic mechanisms and the aim of this study was to test this hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27 years. Compared with normotensive subjects, those with isolated systolic hypertension had significantly higher peripheral, central, and mean blood pressure, aortic pulse wave velocity, cardiac output, and stroke volume (PϽ0.001 for all comparisons). However, there were no differences in pulse pressure amplification, heart rate, or peripheral vascular resistance between the two groups. Compared with subjects with essential hypertension, mean pressure, heart rate, and peripheral vascular resistance were all significantly lower in isolated systolic hypertensive subjects, but pulse pressure amplification, aortic pulse wave velocity, cardiac output, and stroke volume were higher (PϽ0.001 for all comparisons). We have demonstrated that in young adults, isolated systolic hypertension and essential hypertension arise from different hemodynamic mechanisms. Isolated systolic hypertension appears to result from an increased stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality underlying essential hypertension is an increased peripheral vascular resistance. Long-term follow-up of these individuals is now required to determine whether they are at increased risk compared with age-matched normotensive individuals. (Hypertension. 2005;46:221-226.)
European Heart Journal, 2014
Pressure measured with a cuff and sphygmomanometer in the brachial artery is accepted as an impor... more 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 2014 Eighth Joint National Committee panel recommends a therapeutic target of systolic blood ... more The 2014 Eighth Joint National Committee panel recommends a therapeutic target of systolic blood pressure (BP) <150 mm Hg in patients ≥60 years of age, a departure from prior recommendation of <140 mm Hg.
Hypertension, 2012
The significance of white-coat hypertension in older persons with isolated systolic hypertension ... more The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular
Based on individual patient data, we performed a quantitative overview of trials in hypertension ... more Based on individual patient data, we performed a quantitative overview of trials in hypertension to investigate to what extent lowering of systolic blood pressure (SBP) and diastolic blood pressure (DBP) contributed to cardiovascular prevention. We selected trials that tested active antihypertensive drugs against placebo or no treatment. Our analyses included 12 903 young (30 to 49 years of age) patients
American journal of hypertension, 2004
Once considered an inconsequential part of the aging process, an age-associated rise in systolic ... more Once considered an inconsequential part of the aging process, an age-associated rise in systolic blood pressure (SBP) occurs as a consequence of increased arterial stiffness and contributes to a high prevalence of systolic hypertension after middle-age. Elevated SBP imparts a predilection toward the onset of vascular events, highlighting the importance of its control. Current philosophy ranks systolic pressure as the most relevant component of blood pressure (BP) for determining risk for cardiovascular and other events in hypertensive patients, particularly those >50 years of age. Despite its prognostic role, SBP remains more difficult to control than diastolic BP (DBP), and most middle-age and older hypertensive patients fail to achieve recommended targets. In part, the lack of strict control of SBP in the more aged population lies in the physiology of hypertension. Younger persons tend toward isolated diastolic hypertension or combined systolic-diastolic hypertension, primarily...
Journal of the American Society of Hypertension, 2014
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a ra... more The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, doubleblind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 ¼ 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 ¼ 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). Intrial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P ¼ .005, race-by-amlodipine/lisinopril interaction P ¼ .012) and gender (gender-by-lisinopril/amlodipine interaction P ¼ .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period. J Am Soc Hypertens 2014;8(11):808-819.
6 treatment goal of less than 140/90 mmHg, and to less than 130/85 mmHg in those at highest risk,... more 6 treatment goal of less than 140/90 mmHg, and to less than 130/85 mmHg in those at highest risk, especially patients with significant kidney disease or diabetes. We must recommit ourselves to educate, motivate, and treat our patients until they reach the treatment goal that may extend their lives. High blood pressure is endemic in this country. It is our
Journal of the American College of Cardiology, Jan 3, 2015
Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mm Hg and dia... more Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg, in younger and middle-aged adults is increasing in prevalence. The aim of this study was to assess the risk for cardiovascular disease (CVD) with ISH in younger and middle-aged adults. CVD risks were explored in 15,868 men and 11,213 women 18 to 49 years of age (mean age 34 years) at baseline, 85% non-Hispanic white, free of coronary heart disease (CHD) and antihypertensive therapy, from the Chicago Heart Association Detection Project in Industry study. Participant classifications were as follows: 1) optimal-normal blood pressure (BP) (SBP <130 mm Hg and DBP <85 mm Hg); 2) high-normal BP (130 to 139/85 to 89 mm Hg); 3) ISH; 4) isolated diastolic hypertension (SBP <140 mm Hg and DBP ≥90 mm Hg); and 5) systolic diastolic hypertension (SBP ≥140 mm Hg and DBP ≥90 mm Hg). During a 31-year average follow-up period (842,600 person-years), there...
Background—Current definitions of hypertension are based on levels of systolic blood pressure (SB... more Background—Current definitions of hypertension are based on levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), but not on pulse pressure (PP). We examined whether PP adds useful information for predicting coronary heart disease (CHD) in the population-based Framingham Heart Study. Methods and Results—We studied 1924 men and women between 50 and 79 years of age at baseline
Pulse pressure rather than diastolic pressure is the best predictor of coronary heart disease ris... more Pulse pressure rather than diastolic pressure is the best predictor of coronary heart disease risk in older subjects, but the converse is true in younger subjects. We hypothesized that this disparity results from an age-related difference in pressure amplification from the aorta to brachial artery. Data from 212 subjects age 50 years and 230 subjects age 50 years were abstracted
Kidney International, 1975
Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration... more Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration in 30 hemodialysis patients correlated closely with renin concentration, renin activity or renin and potassium concentrations combined (r is greater than or equal to 0.62; P is less than 0.01), and increased consistently in response to upright posture or corticotropin administration. Aldosterone response to hemodialysis was variable. Significant correlations (r is greater than or equal to 0.65; P is less than 0.01) were demonstrated between postural plasma aldosterone and renin responses, between aldosterone responses to corticotropin and basal plasma aldosterone or renin and potassium values, between hemodialysis-induced changes in plasma aldosterone and those in potassium or renin; but not between various indexes of heparin treatment and aldosterone activity. Bilateral nephrectomy reduced basal plasma renin and aldosterone concentrations and aldosterone responsiveness in five preoperatively normoreninemic or hyperreninemic patients, but not in a hyporeninemic patient. These results demonstrate the complementary roles of circulating renin and potassium in the control of aldosterone release under basal and stimulatory conditions in patients with terminal renal failure. Administration of heparin in dosages used during long-term hemodialysis does not appear to significantly interfere with aldosterone control.
Journal of the American Society of Hypertension, 2007
Brachial systolic blood pressure (SBP) is the overall best predictor of future cardiovascular ris... more Brachial systolic blood pressure (SBP) is the overall best predictor of future cardiovascular risk for the entire hypertensive population; however, there is much that can be learned from assessing diastolic blood pressure (DBP) in relation to simultaneous levels of SBP, because the former is not distorted by pressure amplification. Low DBP in very young adults (mean age 20 years), presenting as isolated systolic hypertension (ISH), results from elevation in stroke volume and/or arterial stiffness. This subtype of hypertension has a marked male predominance, occurs twice as frequently as essential hypertension, and is potentially not a benign condition. In contrast, isolated diastolic hypertension (IDH) in young adults (mean age of 40 years) with IDH occurs predominantly in men with a high prevalence of metabolic syndrome. Indeed, persons with IDH frequently evolve into systolic-diastolic hypertension and are potentially at increased risk for future diabetes and cardiovascular complications. The older age population with ISH and low DBP (mean age Ն60 years of age) has a high prevalence of left ventricular hypertrophy, increased ventricular-arterial stiffness, and a tendency for diastolic dysfunction and heart failure. Finally, concordant very high DBP, especially in older persons, defines potential hypertensive urgencies, emergencies, secondary forms of hypertension, and other high peripheral resistance states.
Journal of the American Society of Hypertension, 2008
Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular... more Arterial stiffness of the large, elastic conduit arteries is considered a risk marker of vascular aging, as well as a new biomarker of cardiovascular (CV) disease. Arterial stiffness also plays an important role in the development of isolated systolic hypertension (ISH) in the middle-aged and elderly population. ISH is characterized by an increase in pulse pressure (PP) in association with a rise in systolic blood pressure (SBP) and a fall in diastolic blood pressure (DBP). Increased PP, however, is not always a good surrogate for arterial stiffening because of the frequent discrepancy between peripheral brachial and central aortic PP values due to varying pressure amplification. Therefore, noninvasive, easily performed methods for more direct measurement of arterial stiffness and wave reflection, such as aortic pulse wave velocity (PWV) and pulse wave analysis, have been developed for clinical use. The present review aims to provide an understanding of the pathophysiology of arterial stiffness and wave reflection, to review the various techniques for their measurement, and to explore their usefulness in predicting CV risk and therapeutic benefit in comparison with traditional brachial artery cuff blood pressure (BP) by sphygmomanometry.
Journal of the American College of Cardiology, 2004
In patients with daytime hypertension (HT), Obstructive sleep apnea (OSA) is very often associate... more In patients with daytime hypertension (HT), Obstructive sleep apnea (OSA) is very often associated. The relationship between OSA and daytime HT could be due to many confounding factors such as age, gender, obesity, and race. However, exact mechanism by which OSA can lead to daytime HT is still unclear.
Journal of Human Hypertension, 2004
An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pre... more An increased pulse pressure suggests aortic stiffening. New evidence also suggests that pulse pressure is a more sensitive measure of risk than other indexes of blood pressure in middle-aged and older persons. The objective of the study was to relate pulse pressure to the risk of cardiovascular events in the general population, and to assess whether pulse pressure could improve the Framingham risk prediction. A total of 378 men and 391 women over the age of 50 years (mean 62.7 years) were followed. Sex-specific Framingham cardiovascular risk scores were derived from age, systolic pressure, diastolic pressure, total and HDL cholesterol, smoking status and the presence or absence of diabetes mellitus. The cutoff points used to develop a pulse pressure score were calculated by determining the percentile points corresponding to the blood pressure categories in the Framingham risk score. We calculated relative hazard rates by multiple Cox regression. After a median follow-up of 7.2 years (range: 11 months-15 years), a total of 148 cardiovascular events occurred. In Cox regression analysis, a 10 mmHg higher pulse pressure was associated with 31% (Po0.0001) increase in the risk for cardiovascular events (fatal and nonfatal) after adjustment for sex, age, total and HDL cholesterol, smoking and the presence of diabetes mellitus. After adjustment for the aforementioned risk factors, a onepoint increment in the blood pressure and pulse pressure scores was associated with a 40 and 48% (both Po0.0001) increase in the risk of fatal and nonfatal cardiovascular events, respectively. When both the blood pressure and pulse pressure scores were forced into a Cox model, only the pulse pressure score remained statistically significant (Po0.0001) with a relative hazard rate of 1.37 (CI: 1.16-1.69). These prospective data suggest that pulse pressure may improve the Framingham risk prediction among middle-aged and older individuals. Further studies, especially in the Framingham cohort, are warranted.
The Journal of Clinical Hypertension, 2007
Hypertension treatment guidelines recommend initiating 2-drug therapy whenever blood pressure (BP... more Hypertension treatment guidelines recommend initiating 2-drug therapy whenever blood pressure (BP) is &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =20 mm Hg systolic or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;140 mm Hg or SeDBP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;90 mm Hg; SeSBP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;130 mm Hg or SeDBP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.
The Journal of Clinical Hypertension, 2007
). In 676 (projected to 26.1 million) US persons from the National Health and Nutrition Examinati... more ). 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, lowdensity 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. (J Clin Hypertens. 2007;9:436-443)
Hypertension, 2012
The significance of white-coat hypertension in older persons with isolated systolic hypertension ... more The significance of white-coat hypertension in older persons with isolated systolic hypertension remains poorly understood. We analyzed subjects from the population-based 11-country International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular
Hypertension, 2013
Although distinguishing features of masked hypertension in diabetics are well known, the signific... more Although distinguishing features of masked hypertension in diabetics are well known, the significance of antihypertensive treatment on clinical practice decisions has not been fully explored. We analyzed 9691 subjects from the population-based 11-country International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes. Prevalence of masked hypertension in untreated normotensive participants was higher (P<0.0001) among 229
Hypertension, 2005
Isolated systolic hypertension is a common condition in individuals aged older than 60 years. How... more Isolated systolic hypertension is a common condition in individuals aged older than 60 years. However, isolated systolic hypertension has also been described in young individuals, although the mechanisms are poorly understood. We hypothesized that in young adults, isolated systolic hypertension and essential hypertension have different hemodynamic mechanisms and the aim of this study was to test this hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27 years. Compared with normotensive subjects, those with isolated systolic hypertension had significantly higher peripheral, central, and mean blood pressure, aortic pulse wave velocity, cardiac output, and stroke volume (PϽ0.001 for all comparisons). However, there were no differences in pulse pressure amplification, heart rate, or peripheral vascular resistance between the two groups. Compared with subjects with essential hypertension, mean pressure, heart rate, and peripheral vascular resistance were all significantly lower in isolated systolic hypertensive subjects, but pulse pressure amplification, aortic pulse wave velocity, cardiac output, and stroke volume were higher (PϽ0.001 for all comparisons). We have demonstrated that in young adults, isolated systolic hypertension and essential hypertension arise from different hemodynamic mechanisms. Isolated systolic hypertension appears to result from an increased stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality underlying essential hypertension is an increased peripheral vascular resistance. Long-term follow-up of these individuals is now required to determine whether they are at increased risk compared with age-matched normotensive individuals. (Hypertension. 2005;46:221-226.)
European Heart Journal, 2014
Pressure measured with a cuff and sphygmomanometer in the brachial artery is accepted as an impor... more 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.