Brent M. Egan

US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008.

CONTEXT Hypertension is a major risk factor for cardiovascular disease and treatment and control of hypertension reduces risk. The Healthy People 2010 goal was to achieve blood pressure (BP) control in 50% of the US population. OBJECTIVE To assess progress in treating and controlling hypertension in the United States from 1988-2008. DESIGN, SETTING, AND PARTICIPANTS The National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2008 in five 2-year blocks included 42 856 adults aged older than 18 years, representing a probability sample of the US civilian population. MAIN OUTCOME MEASURES Hypertension was defined as systolic BP of at least 140 mm Hg and diastolic BP of at least 90 mm Hg, self-reported use of antihypertensive medications, or both. Hypertension control was defined as systolic BP values of less than 140 mm Hg and diastolic BP values of less than 90 mm Hg. All survey periods were age-adjusted to the year 2000 US population. RESULTS Rates of hypertension increased from 23.9% (95% confidence interval [CI], 22.7%-25.2%) in 1988-1994 to 28.5% (95% CI, 25.9%-31.3%; P < .001) in 1999-2000, but did not change between 1999-2000 and 2007-2008 (29.0%; 95% CI, 27.6%-30.5%; P = .24). Hypertension control increased from 27.3% (95% CI, 25.6%-29.1%) in 1988-1994 to 50.1% (95% CI, 46.8%-53.5%; P = .006) in 2007-2008, and BP among patients with hypertension decreased from 143.0/80.4 mm Hg (95% CI, 141.9-144.2/79.6-81.1 mm Hg) to 135.2/74.1 mm Hg (95% CI, 134.2-136.2/73.2-75.0 mm Hg; P = .02/P < .001). Blood pressure control improved significantly more in absolute percentages between 1999-2000 and 2007-2008 vs 1988-1994 and 1999-2000 (18.6%; 95% CI, 13.3%-23.9%; vs 4.1%; 95% CI, -0.5% to 8.8%; P < .001). Better BP control reflected improvements in awareness (69.1%; 95% CI, 67.1%-71.1%; vs 80.7%; 95% CI, 78.1%-83.0%; P for trend = .03), treatment (54.0%; 95% CI, 52.0%-56.1%; vs 72.5%; 95% CI, 70.1%-74.8%; P = .004), and proportion of patients who were treated and had controlled hypertension (50.6%; 95% CI, 48.0%-53.2%; vs 69.1%; 95% CI, 65.7%-72.3%; P = .006). Hypertension control improved significantly between 1988-1994 and 2007-2008, across age, race, and sex groups, but was lower among individuals aged 18 to 39 years vs 40 to 59 years (P < .001) and 60 years or older (P < .001), and in Hispanic vs white individuals (P = .004). CONCLUSIONS Blood pressure was controlled in an estimated 50.1% of all patients with hypertension in NHANES 2007-2008, with most of the improvement since 1988 occurring after 1999-2000. Hypertension control was significantly lower among younger than middle-aged individuals and older adults, and Hispanic vs white individuals.

Therapeutic Inertia Is an Impediment to Achieving the Healthy People 2010 Blood Pressure Control Goals

Therapeutic inertia (TI), defined as the providers’ failure to increase therapy when treatment goals are unmet, contributes to the high prevalence of uncontrolled hypertension (≥140/90 mm Hg), but the quantitative impact is unknown. To address this gap, a retrospective cohort study was conducted on 7253 hypertensives that had ≥4 visits and ≥1 elevated blood pressure (BP) in 2003. A 1-year TI score was calculated for each patient as the difference between expected and observed medication change rates with higher scores reflecting greater TI. Antihypertensive therapy was increased on 13.1% of visits with uncontrolled BP. Systolic BP decreased in patients in the lowest quintile of the TI score but increased in those in the highest quintile (−6.8±0.5 versus +1.8±0.6 mm Hg; P<0.001). Individuals in the lowest TI quintile were ≈33 times more likely to have their BP controlled at the last visit than those in highest quintile (odds ratio, 32.7; 95% CI, 25.1 to 42.6; P<0.0001). By multivariable analysis, TI accounted for ≈19% of the variance in BP control. If TI scores were decreased ≈50%, that is, increasing medication dosages on ≈30% of visits, BP control would increase from the observed 45.1% to a projected 65.9% in 1 year. This study confirms the high rate of TI in uncontrolled hypertensive subjects. TI has a major impact on BP control in hypertensive subjects receiving regular care. Reducing TI is critical in attaining the Healthy People 2010 goal of controlling hypertension in 50% of all patients.

Uncontrolled and Apparent Treatment Resistant Hypertension in the United States, 1988 to 2008

Background— Despite progress, many hypertensive patients remain uncontrolled. Defining characteristics of uncontrolled hypertensives may facilitate efforts to improve blood pressure control. Methods and Results— Subjects included 13 375 hypertensive adults from National Health and Nutrition Examination Surveys (NHANESs) subdivided into 1988 to 1994, 1999 to 2004, and 2005 to 2008. Uncontrolled hypertension was defined as blood pressure ≥140/≥90 mm Hg and apparent treatment-resistant hypertension (aTRH) when subjects reported taking ≥3 antihypertensive medications. Framingham 10-year coronary risk was calculated. Multivariable logistic regression was used to identify clinical characteristics associated with untreated, treated uncontrolled on 1 to 2 blood pressure medications, and aTRH across all 3 survey periods. More than half of uncontrolled hypertensives were untreated across surveys, including 52.2% in 2005 to 2008. Clinical factors linked with untreated hypertension included male sex, infrequent healthcare visits (0 to 1 per year), body mass index <25 kg/m2, absence of chronic kidney disease, and Framingham 10-year coronary risk <10% (P<0.01). Most treated uncontrolled patients reported taking 1 to 2 blood pressure medications, a proxy for therapeutic inertia. This group was older, had higher Framingham 10-year coronary risk than patients controlled on 1 to 2 medications (P<0.01), and comprised 34.4% of all uncontrolled and 72.0% of treated uncontrolled patients in 2005 to 2008. We found that aTRH increased from 15.9% (1998–2004) to 28.0% (2005–2008) of treated patients (P<0.001). Clinical characteristics associated with aTRH included ≥4 visits per year, obesity, chronic kidney disease, and Framingham 10-year coronary risk >20% (P<0.01). Conclusion— Untreated, undertreated, and aTRH patients have consistent characteristics that could inform strategies to improve blood pressure control by decreasing untreated hypertension, reducing therapeutic inertia in undertreated patients, and enhancing therapeutic efficiency in aTRH.

Prehypertension and Cardiovascular Morbidity

PURPOSE The Seventh Report of the Joint National Commission (JNC 7) on High Blood Pressure established prehypertension (120 to 139 mm Hg systolic or 80 to 89 mm Hg diastolic) as a new risk category. We aim to determine the risk of major cardiovascular events associated with blood pressure in the prehypertensive range in a longitudinal, population-based cohort. METHODS Analyses were conducted on participants in the National Health and Nutrition Examination Survey I (1971–1975) observed for 18 years for major cardiovascular disease events. Cox proportional hazard ratios were calculated to assess relative risk of cardiovascular disease, including stroke, myocardial infarction, and heart failure, in participants with prehypertension and normal blood pressure (<120/80 mm Hg). RESULTS Prehypertension was associated with increased risk for cardiovascular disease (1.79 [95% confidence interval (CI) 1.40–2.24]) in unadjusted analysis. After adjustment for cardiovascular risk factors, the relationship of prehypertension to cardiovascular disease was diminished but persisted (1.32 [95% CI 1.05–1.65]). Ninety-three percent of prehypertensive individuals had at least 1 cardiovascular risk factor. Low prehypertension (120–129/80–84 mm Hg) was associated with increased cardiovascular disease in unadjusted analyses (1.56 [95% CI 1.23–1.98]) but was not statistically significant in adjusted analyses (1.24 [95% CI 0.96–1.59]). High-normal blood pressure (130–139/85–89 mm Hg) remained a predictor of cardiovascular disease in unadjusted (2.13 [95% CI 1.64–2.76]) and adjusted (1.42 [95% CI 1.09–1.84]) analyses. CONCLUSIONS In a longitudinal, population-based, US cohort, prehypertension was associated with increased risk of major cardiovascular events independently of other cardiovascular risk factors. These findings, along with the presence of cardiovascular risk factors in the majority of participant sample with prehypertension, support recommendations for physicians to actively target lifestyle modifications and multiple risk reduction in their prehypertensive patients.

Oleic Acid Inhibits Endothelial Nitric Oxide Synthase by a Protein Kinase C–Independent Mechanism

Many obese hypertensive individuals have a cluster of cardiovascular risk factors. This cluster includes plasma nonesterified fatty acid concentrations and turnover rates that are higher and more resistant to suppression by insulin than in lean and obese normotensive individuals. The higher fatty acids may contribute to cardiovascular risk in these patients by inhibiting endothelial cell nitric oxide synthase activity. To test this hypothesis, we quantified the effects of oleic (18:1[cis]) and other 18-carbon fatty acids on nitric oxide synthase activity in cultured bovine pulmonary artery endothelial cells by measuring the conversion of [3H]L-arginine to [3H]L-citrulline. Oleic acid (from 10 to 100 mumol/L) caused a concentration-dependent decrease in nitric oxide synthase activity at baseline and during ATP and ionomycin (Ca2+ ionophore) stimulation. At 100 mumol/L, linoleic (18:2[cis]) and oleic acids caused similar reductions of nitric oxide synthase activity, whereas elaidic (18:1[trans]) and stearic (18:0) acids had no effect. Oleic acid also inhibited the endothelium-dependent vasodilator response to acetylcholine in rabbit femoral artery rings preconstricted with phenylephrine (P < .05) but had no effect on the response to nitroprusside. The pattern of 18-carbon fatty acid effects on nitric oxide synthase activity in endothelial cells is consistent with activation of protein kinase C. Although oleic acid increased protein kinase C activity in endothelial cells, neither depletion of protein kinase C by 24-hour pretreatment with phorbol 12-myristate 13-acetate nor its inhibition with staurosporine eliminated the inhibitory effect of oleic acid on nitric oxide synthase.(ABSTRACT TRUNCATED AT 250 WORDS)

Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion

Abstract—Plasma levels of aldosterone are not always predictable from the activity of renin and the concentration of potassium. Among the unexplained are elevated levels of aldosterone in some obese humans. Obesity is characterized by increased plasma fatty acids and oxidative stress. We postulated that oxidized fatty acids stimulate aldosteronogenesis. The most readily oxidized fatty acids are the polyunsaturated, and the most abundant of those is linoleic acid. We tested oxidized derivatives of linoleic acid for effects on rat adrenal cells. One derivative, 12,13-epoxy-9-keto-10(trans)-octadecenoic acid (EKODE), was particularly potent. EKODE stimulated aldosteronogenesis at concentrations from 0.5 to 5 &mgr;mol/L, and inhibited aldosteronogenesis at higher doses. EKODE’s stimulatory effect was most prominent when angiotensin and potassium effects were submaximal. The lipid’s mechanism of action was on the early pathway leading to pregnenolone; its action was inhibited by atrial natriuretic peptide. Plasma EKODE was measured by liquid chromatography/mass spectrometry. All human plasmas tested contained EKODE in concentrations ranging from 10−9 to 5×10−7 mol/L. In samples from 24 adults, levels of EKODE correlated directly with aldosterone (r =0.53, P =0.007). In the 12 blacks in that cohort, EKODE also correlated with body mass index and systolic pressure. Those other correlations were not seen in white subjects. The results suggest that oxidized derivatives of polyunsaturated fatty acids other than arachidonic are biologically active. Compounds like EKODE, derived from linoleic acid, may affect adrenal steroid production in humans and mediate some of the deleterious effects of obesity and oxidative stress, especially in blacks.

Cost-effectiveness and clinical effectiveness of catheter-based renal denervation for resistant hypertension

OBJECTIVES The purpose of this study was to assess cost-effectiveness and long-term clinical benefits of renal denervation in resistant hypertensive patients. BACKGROUND Resistant hypertension affects 12% of hypertensive persons. In the Symplicity HTN-2 randomized controlled trial, catheter-based renal denervation (RDN) lowered systolic blood pressure by 32 ± 23 mm Hg from 178 ± 18 mm Hg at baseline. METHODS A state-transition model was used to predict the effect of RDN and standard of care on 10-year and lifetime probabilities of stroke, myocardial infarction, all coronary heart disease, heart failure, end-stage renal disease, and median survival. We adopted a societal perspective and estimated an incremental cost-effectiveness ratio in U.S. dollars per quality-adjusted life-year, both discounted at 3% per year. Robustness and uncertainty were evaluated using deterministic and probabilistic sensitivity analyses. RESULTS Renal denervation substantially reduced event probabilities (10-year/lifetime relative risks: stroke 0.70/0.83; myocardial infarction 0.68/0.85; all coronary heart disease 0.78/0.90; heart failure 0.79/0.92; end-stage renal disease 0.72/0.81). Median survival was 18.4 years for RDN versus 17.1 years for standard of care. The discounted lifetime incremental cost-effectiveness ratio was

Hypertension-Related Morbidity and Mortality in the Southeastern United States

3,071 per quality-adjusted life-year. Findings were relatively insensitive to variations in input parameters except for systolic blood pressure reduction, baseline systolic blood pressure, and effect duration. The 95% credible interval for incremental cost-effectiveness ratio was cost-saving to

DASH Diet Lowers Blood Pressure and Lipid-Induced Oxidative Stress in Obesity

31,460 per quality-adjusted life-year. CONCLUSIONS The model suggests that catheter-based renal denervation, over a wide range of assumptions, is a cost-effective strategy for resistant hypertension that might result in lower cardiovascular morbidity and mortality.

Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial.

Stroke mortality is higher in the Southeast compared with other regions of the United States. The prevalence of hypertension is also higher (black men = 35%, black women = 37.7%, white men = 26.5%, white women = 21.5%), and the proportion of patients whose hypertension is being controlled is poor, especially in white and black men. The prevalence of hypertension-related complications other than stroke is also higher in the Southeast. The five states with the highest death rates for congestive heart failure are all in the southern region. Of the 15 states with the highest rates of end-stage renal disease, 10 are in the Southeast. Obesity is very prevalent (24% to 28%) in the Southeast. Although Michigan tops the ranking for all states, 6 of the top 15 states are in the Southeast, as are 7 of the 10 states with the highest reported prevalence regarding no leisure-time physical activity. Similar to other areas of the United States, dietary sodium and saturated fat intake are high in the Southeast; dietary potassium intake appears to be relatively low. Other factors that may be associated with the high prevalence, poor control, and excess morbidity and mortality of hypertension-related complications in the Southeast include misperceptions of the seriousness of the problem, the severity of the hypertension, lack of adequate follow-up, reduced access to health care, the cost of treatment, and possibly, low birth weights. The Consortium of Southeastern Hypertension Control (COSEHC) is a nonprofit organization created in 1992 in response to a compelling need to improve the disproportionate hypertension-related morbidity and mortality throughout this region. The purpose of this position paper is to summarize the data that document the problem, the consequences, and possible causative factors.