Abstract: Mercury has a high affinity for sulfhydryl groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (N-acetyl-L-cysteine, alpha-lipoic acid, L-glutathione), with subsequent decreased oxidant defense and increased oxidative stress. Mercury binds to metallothionein and substitute for zinc, copper, and other trace metals, reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in adenosine triphosphate, depletion of glutathione, and increased lipid peroxidation. Increased oxidative stress and reduced oxidative defense are common. Selenium and fish containing omega-3 fatty acids antagonize mercury toxicity. The overall vascular effects of mercury include increased oxidative stress and inflammation, reduced oxidative defense, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, and immune and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, coronary heart disease, myocardial infarction, cardiac arrhythmias, reduced heart rate variability, increased carotid intima-media thickness and carotid artery obstruction, cerebrovascular accident, generalized atherosclerosis, and renal dysfunction, insufficiency, and proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury inactivates catecholaminei-0-methyl transferase, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to mercury-induced heavy metal toxicity. Mercury toxicity should be evaluated in any patient with hypertension, coronary heart disease, cerebral vascular disease, cerebrovascular accident, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, and serum should be performed.

Abstract: KEY POINTS AND PRACTICAL RECOMMENDATIONS: • Calcium channel blockers, which dilate arteries by reducing calcium flux into cells, effectively lower blood pressure, especially in combination with other drugs, and some formulations of agents of this class are approved for treating angina or cardiac dysrhythmias. • Calcium channel blockers reduce blood pressure across all patient groups, regardless of sex, race/ethnicity, age, and dietary sodium intake. • Nondihydropyridine calcium channel blockers are more negatively chronotropic and inotropic than the dihydropyridine subclass, which is important for patients with cardiac dysrhythmias or who need β-blockers. • Extensive experience in comparative randomized trials indicates that an initial calcium antagonist can prevent all major types of cardiovascular disease, except heart failure (for which a diuretic is superior). Initial dihydropyridine calcium channel blockers have not reduced the rate of progression of renal disease as well as inhibitors of the renin-angiotensin system, although members of the nondihydropyridine subclass can reduce albuminuria. • High doses of dihydropyridine calcium channel blockers often cause edema, headache, flushing and tachycardia; high doses of verapamil can cause constipation. Diltiazem and verapamil have important drug interaction with digoxin and cyclosporine, among others.

Abstract: Hypertension is associated with increased left ventricular mass (LVM) and carotid intima-media thickness (cIMT), which predict cardiovascular (CV) events in adults. Whether target organ damage is found in pre-hypertensive youth is not known. The authors measured body mass index, blood pressure, fasting glucose, insulin, lipids and C-reactive protein, LVM/height(2.7) (LVM index), diastolic function, cIMT, carotid stiffness, augmentation index, brachial artery distensibility, and pulse wave velocity (PWV) in 723 patients aged 10 to 23 years (29% with type 2 diabetes mellitus). Patients were stratified by blood pressure level (normotensive: 531, pre-hypertensive: 65, hypertensive: 127). Adiposity and CV risk factors worsened across blood pressure group. There was a graded increase in cIMT, arterial stiffness, and LVM index and decrease in diastolic function from normotension to pre-hypertension to hypertension. In multivariable models adjusted for CV risk factors, status as pre-hypertension or hypertension remained an independent determinant of target organ damage for LVM, diastolic function, internal cIMT, and carotid and arterial stiffness. Pre-hypertension is associated with cardiovascular target organ damage in adolescents and young adults.

Abstract: Magnesium intake of 500 mg/d to 1000 mg/d may reduce blood pressure (BP) as much as 5.6/2.8 mm Hg. However, clinical studies have a wide range of BP reduction, with some showing no change in BP. The combination of increased intake of magnesium and potassium coupled with reduced sodium intake is more effective in reducing BP than single mineral intake and is often as effective as one antihypertensive drug in treating hypertension. Reducing intracellular sodium and calcium while increasing intracellular magnesium and potassium improves BP response. Magnesium also increases the effectiveness of all antihypertensive drug classes. It remains to be conclusively proven that cardiovascular disease such as coronary heart disease, ischemic stroke, and cardiac arrhythmias can be prevented or treated with magnesium intake. Preliminary evidence suggests that insulin sensitivity, hyperglycemia, diabetes mellitus, left ventricular hypertrophy, and dyslipidemia may be improved with increased magnesium intake. Various genetic defects in magnesium transport are associated with hypertension and possibly with cardiovascular disease. Oral magnesium acts as a natural calcium channel blocker, increases nitric oxide, improves endothelial dysfunction, and induces direct and indirect vasodilation.

Abstract: J Clin Hypertens (Greenwich). 2011;13:739–743. ©2011 Wiley Periodicals, Inc. Sleep is a contributing factor to optimal health and vitality. However, to date, no national study has evaluated the simultaneous relationship between sleep disorders, quality, and duration with hypertension. Using data from National Health and Nutrition Examination Survey (NHANES) (2005 to 2008), hypertension was defined by current use of antihypertensive medication or systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Self-reported sleep disorders and duration were categorized from a single household interview question, and sleep quality was determined from several questions on sleeping habits. The prevalence of hypertension was 30.2% and 7.5%, and 33.0% and 52.1% reported having sleep disorders, short sleep, and poor sleep, respectively. After adjustment for demographic characteristics and comorbidities, having sleep disorders only was not significantly associated with hypertension (odds ratio [OR], 1.65; 95% confidence interval [CI], 0.73−3.77). However, this association was modified by sleep duration: significant associations were observed among adults with concurrent sleep disorders and short sleep (OR, 2.30; 95% CI, 1.49−3.56) and with sleep disorders, short sleep, and poor sleep (OR, 1.84; 95% CI, 1.13−2.98). These findings indicate an association between a combination of sleep problems and hypertension, but prospective studies are needed to understand the complex interplay between them.

Abstract: J Clin Hypertens (Greenwich). 2011;13:639–643. ©2011 Wiley Periodicals, Inc. Key Points and Practical Recommendations • Although chlorthalidone and hydrochlorothiazide are structurally similar, they are very different pharmacokinetically, with chlorthalidone having both an extremely long half-life (approximately 40 to 60 hours) and a large volume of distribution, with gradual elimination from the plasma compartment by tubular secretion. • Furosemide usage, the most widely used diuretic in the loop diuretic class, can be complicated by extremely erratic absorption, with a bioavailability range of 12% to 112%. • Chlorthalidone, at a dose of 25 mg, is comparatively more potent than 50 mg of hydrochlorothiazide, particularly as related to overnight blood pressure reduction. • In ALLHAT, there was no difference among chlorthalidone, amlodipine, lisinopril, and doxazosin for the primary outcome or mortality. • Secondary outcomes were similar except for a 38% higher rate of heart failure with amlodipine; a 10% higher rate of combined cardiovascular disease, a 15% higher rate of stroke, and a 19% higher rate of heart failure with lisinopril; and a 20% higher rate of cardiovascular disease, a 20% higher rate of stroke (40% higher rate in blacks), and an 80% higher rate of heart failure with doxazosin, compared with chlorthalidone. • The ACCOMPLISH study may affect future practice guidelines as a result of its findings favoring the amlodipine/benazepril combination; however, the generalizability to patient populations with a lesser cardiovascular risk profile remains in question and the dose of hydrochlorothiazide was only 12.5 mg to 25 mg daily, which was a dose lower than that used in placebo-controlled trials using hydrochlorothiazide. • Certain low-renin patient groups (eg, blacks, the elderly, and diabetics) as well as those who manifest the metabolic syndrome are commonly more responsive to thiazide-type diuretic therapy. • Diuretics can be successfully combined with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, centrally acting agents, and even calcium channel blockers. • Although thiazide-type diuretics are among the best-tolerated antihypertensive agents in terms of symptomatic adverse effects, diuretic-related adverse side effects include those with established mechanisms (eg, such as electrolyte changes and/or metabolic abnormalities) and other side effects, which are less well understood mechanistically (eg, impotence), although the latter is not universally accepted as a diuretic-related side effect. • Thiazide-induced hypokalemia is associated with increased blood glucose, and treatment of thiazide-induced hypokalemia may reverse glucose intolerance and possibly prevent diabetes. • Thiazide-induced hyperuricemia occurs as a result of volume contraction and competition with uric acid for renal tubular secretion, but does not necessarily contraindicate using a thiazide, especially if a uric acid–lowering drug such as allopurinol is being used. • Adverse interactions include the blunting of thiazide effects by nonsteroidal anti-inflammatory drugs and the potential to increase fatigue, lethargy, and increase in glucose when combined with β-blockers. • Thiazide-type diuretics are useful first-line agents in the treatment of hypertension because they have been proven to reduce cardiovascular mortality and morbidity in systolic and diastolic forms of hypertension and do so at low cost. • Loop diuretics should not be used as first-line therapy in hypertension since there are no outcome data with them. They should be reserved for conditions of clinically significant fluid overload (eg, heart failure and significant fluid retention with vasodilator drugs, such as minoxidil) or with advanced renal failure and can be combined with thiazide-type diuretics.

Abstract: J Clin Hypertens (Greenwich) 2011;13:898–909 ©2011 Wiley Periodicals, Inc This meta-analysis compares health care resource use costs, adherence, and persistence between groups of patients taking antihypertensives as single-pill combinations (SPCs) vs free-equivalent components (FEC) based on a structured review of published studies The search yielded 12 retrospective database studies included in analyses The mean difference in combined total annual all-cause and hypertension-related health care costs was $1357 (95% confidence interval [CI], $778–$1935) lower in favor of SPC than FEC groups Adherence, measured as the mean difference in medication possession ratio, was estimated to be 8% higher for patients naive to prior antihypertensives and 14% higher for nonnaive SPC patients compared with corresponding FEC patients Persistence in the SPC groups was twice as likely as the FEC groups (pooled risk ratio, 21; 95% CI, 11–41) Improved adherence and persistence may have contributed to the lower costs in the SPC groups via improved clinical outcomes

Abstract: Insulin resistance plays a major role in the pathogenesis and clinical course of patients with type 2 diabetes (2DM) and essential hypertension. However, the syndromes differ in prevalence of insulin resistance, and associated insulin secretory response. Essentially all patients with type 2 diabetes are insulin resistant, whereas only approximately 50% of those with essential hypertension are insulin resistant. Furthermore, 2DM develops when the pancreatic β-cell can no longer maintain the degree of compensatory hyperinsulinemia needed to prevent hyperglycemia. In contrast, the compensatory hyperinsulinemia that prevents most insulin resistant individuals from developing 2DM acts on normally insulin sensitive tissues in a manner that predisposes to the development of essential hypertension. This review will discuss these similarities and differences in some detail, as well as exploring the relationship among insulin resistance and related metabolic abnormalities in the pathogenesis of cardiovascular disease in patients with 2DM and essential hypertension.

Abstract: The current study assesses the antihypertensive efficacy and safety of the investigational angiotensin receptor blocker (ARB), azilsartan medoxomil (AZL-M), compared with placebo and the ARB olmesartan medoxomil (OLM-M). This randomized, double-blind, placebo-controlled, multicenter study assessed change from baseline in mean 24-hour ambulatory systolic blood pressure (SBP) following 6 weeks of treatment. Patients with primary hypertension (n=1275) and baseline 24-hour mean ambulatory systolic pressure ≥ 130 mm Hg and ≤ 170 mm Hg were studied; 142 received placebo and the remainder received 20 mg, 40 mg, or 80 mg AZL-M or 40 mg OLM-M. Mean age of participants was 58 ± 11 years, baseline mean 24-hour SBP was 146 mm Hg. Dose-dependent reductions in 24-hour mean SBP at study end occurred in all AZL-M groups. Reduction in 24-hour mean SBP was greater with AZL-M 80 mg than OLM-M 40 mg by 2.1 mm Hg (95% confidence interval, -4.0 to -0.1; P=.038), while AZL-M 40 mg was noninferior to OLM-M 40 mg. The side effect profiles of both ARBs were similar to placebo. AZL-M is well tolerated and more efficacious at its maximal dose than the highest dose of OLM-M.

Abstract: Activation of the renin-angiotensin-aldosterone system (RAAS) is the primary etiologic event in the development of hypertension in people with diabetes mellitus. Modulation of the RAAS has been shown to slow the progression and even cause regression of the microvascular and macrovascular complications associated with diabetes mellitus. Early pharmacotherapy with agents that decrease RAAS activation in the adipose tissue have had a dramatic impact on the prevalence of diabetes related complications. Recent data show that preventing the development of "angry fat" can prevent not just hypertension but also type 2 diabetes mellitus and its associated complications. This review updates what is known about angry fat and the role of RAAS inhibition in preventing the metabolic sequelae of local RAAS activation.

Abstract: J Clin Hypertens (Greenwich). 2011;13:667–675. ©2011 Wiley Periodicals, Inc. Key Points and Recommendations • In addition to hypertension, angiotensin-converting enzyme inhibitors are indicated for treatment of patients at high risk for coronary artery disease, after myocardial infarction, with dilated cardiomypathy, or with chronic kidney disease. • The most familiar angiotensin-converting enzyme subtype, angiotensin-converting enzyme-1 (kininase II), cleaves the vasoconstrictor octapeptide angiotensin II from its inactive decapeptide precursor, angiotensin I, while simultaneously inactivating the vasodilator bradykinin. • Biochemical pathways within and around the renin-angiotensin system are highly species-specific; there is little evidence that “angiotensin-converting enzyme bypass pathways” have major clinical implications in humans. • Dietary sodium loading can diminish or abolish the antihypertensive effect of an angiotensin-converting enzyme inhibitor, while salt restriction or concomitant diuretic therapy enhances it. • Dose-response curves with angiotensin-converting enzyme inhibitors are quite flat but their peak effects vary in different individuals. • Increased serum creatinine (decreased glomerular filtration rate) during acute or chronic angiotensin-converting enzyme inhibition identifies individuals likely to experience long-term renal protective benefits. • Angiotensin-converting enzyme inhibitors are contraindicated in pregnancy due to fetal toxicity. • Use of angiotensin-converting enzymes can be limited by idiosyncratic reactions (cough or angioedema), hyperkalemia (usually in cardiac or renal failure or with combined renin-angiotensin blockade) or hypotension (usually with severe volume-depletion or cardiac failure).

Abstract: Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double-blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24-hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP (-14.9 mm Hg and -15.3 mm Hg, respectively) more than VAL 320 mg (-11.3 mm Hg; P<.001 for 40-mg and 80-mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results (-14.9 mm Hg for AZL-M 40 mg and -16.9 mm Hg for AZL-M 80 mg vs -11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL (P≤.001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL-M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class.

Abstract: KEY POINTS AND PRACTICAL RECOMMENDATIONS: • β-Blockers are appropriate treatment for patients with hypertension and those who have concomitant ischemic heart disease, heart failure, obstructive cardiomyopathy, or certain arrhythmias. • β-Blockers can be used in combination with other antihypertensive drugs to achieve maximal blood pressure control. Labetalol can be used in hypertensive emergencies and urgencies. • β-Blockers may be useful in patients having hyperkinetic circulation (palpitations, tachycardia, hypertension, and anxiety), migraine headache, and essential tremor. • β-Blockers are highly heterogeneous with respect to various pharmacologic effects: degree of intrinsic sympathomimetic activity, membrane-stabilizing activity, β(1) selectivity, α(1) -adrenergic-blocking effect, tissue solubility, routes of systemic elimination, potencies and duration of action, and specific effects may be important in the selection of a drug for clinical use. • β-Blocker usage to reduce perioperative ischemia and cardiovascular complications may not benefit as many patients as was once hoped and may actually cause harm in some individuals. Currently the best evidence supports β-blocker use in two patient groups: patients undergoing vascular surgery with known ischemic heart disease or multiple risk factors for it and for patients already receiving β-blockers for known cardiovascular conditions.

Abstract: J Clin Hypertens (Greenwich). 2011;13:677–686. ©2011 Wiley Periodicals, Inc. Key Points and Practical Recommendations • The angiotensin receptor blockers are highly effective antihypertensive agents that are also particularly well tolerated. • There are no major differences in efficacy or other clinical characteristics among older drugs in this class, although some of the newer agents may more effectively reduce blood pressure than older agents. • Major randomized clinical trials have demonstrated that angiotensin receptor blockers provide significant outcomes benefits in conditions such as diabetic nephropathy, chronic heart failure or heart failure following myocardial infarction, hypertension with left ventricular hypertrophy and in patients whose histories of previous events or complicated diabetes puts them at high cardiovascular risk. • In treating hypertension, angiotensin receptor blockers can be used as first-line therapy or added at later stages of treatment titration. • These drugs are very effective in combination with thiazide diuretics or calcium channel blockers and there are several single-pill, fixed-dose combinations of angiotensin receptor blockers with hydrochlorothiazide, amlodipine, or aliskiren. These combinations can be given as initial therapy (where appropriate) or later in the course of treatment. Three-drug combinations (angiotensin receptor blocker plus amlodipine plus hydrochlorothiazide and angiotensin receptor blocker plus aliskiren plus hydrochlorothiazide) are also available.

Abstract: The prevalence of hypertension among all adolescents is approximately 3.5%, with somewhat higher rates of prehypertension. Obesity affects approximately 20% of adolescents in the United States, and the prevalence of hypertension is much higher among obese adolescents compared with nonobese adolescents. As in other populations, the evaluation of elevated blood pressure in obese adolescents should begin with a confirmation of the blood pressure elevation, followed by a focused diagnostic work-up to detect possible secondary causes of hypertension. Primary therapy for obesity-related hypertension in adolescents begins with weight loss, and may include antihypertensive medications if target-organ damage or other indications for drug therapy are present. The emphasis of management should be reduction of future cardiovascular risk.

Abstract: The metabolic syndrome is an emerging clinical problem and different kinds of interventions have emphasized that healthy eating and exercise are crucial to its control. The aim of this study was to identify whether aerobic training plus resistance training (AT+RT) is more effective than AT on improving features of the metabolic syndrome and adiponectinemia in obese adolescents. A total of 30 adolescents (aged 15-19 years, body mass index ≥95 percentile) were enrolled in the program. All patients were diagnosed with the metabolic syndrome and submitted to 1 year of interdisciplinary intervention. They were divided into two groups: AT (n=15) and AT+RT (n=15). Blood samples were collected to analyze glycemia and lipid profiles. Adiponectin was measured by enzyme-linked immunosorbent assay, and insulin resistance was measured by homeostasis model assessment of insulin resistance index. After short- and long-term intervention, both groups presented a significant reduction in body mass, body mass index, fat mass, and visceral fat. Indeed, the AT+RT group had significantly higher changes throughout the intervention in body composition, total cholesterol, waist circumference, glucose, and adiponectin. Although important clinical parameters were ameliorated with AT, the AT+RT group showed more effective improvements in metabolic profiles and adiponectinemia. These findings suggest a clinical role of AT+RT in the control of metabolic syndrome in pediatric populations.

Abstract: Resistant hypertension is an entity that has gained a lot of attention in recent years. The prevalence and prognosis of resistant hypertension have not yet been examined by proper population studies, but data from several sources suggest that this entity is not uncommon and is associated with an elevated risk of hypertensive complications. Moreover, several factors and conditions that can interfere with blood pressure control such as excess sodium intake, obesity, diabetes, older age, kidney disease, and certain identifiable causes of hypertension were shown to be common among patients with resistance to antihypertensive treatment. Importantly, the prevalence of several of these conditions has been increasing continuously during the past years, suggesting a future increase in the frequency of resistant hypertension. This article will discuss current knowledge and associated future implications relevant to the epidemiology of resistant hypertension.

Abstract: Spironolactone, a nonselective mineralocorticoid receptor (MR) antagonist, has been in clinical use for several decades. A selective MR antagonist (eplerenone) has also been developed and is now in clinical use. Before proceeding to review the use of these drugs in clinical practice, we will briefly review how the aldosterone paradigm and current concepts of the mineralocorticoid receptor have changed.

Abstract: Vitamin D deficiency has been linked to cardiovascular disease and risk factors including hypertension. The authors sought to determine prevalence rates of hypertension in adults tested for 25-hydroxyvitamin D categorized by their levels and evaluate odds ratios for hypertension at lower 25-hydroxyvitamin D levels compared with optimal levels. A cross-sectional study was conducted January 1, 2004, through December 31, 2006, of patients aged 18 years and older within a large ethnically diverse population. Diagnosis of hypertension was determined by International Statistical Classification of Diseases and Related Health Problems codes. Patients were categorized into quartiles according to 25-hydroxyvitamin D levels: ideal (≥40 ng/mL), adequate (30-39 ng/mL), deficient (15-29 ng/mL), and severely deficient (<15 ng/mL). Prevalence rates of hypertension and odds ratios were calculated for each 25-hydroxyvitamin D quartile, adjusting for age, sex, race, and renal insufficiency. A total of 2722 individuals met the inclusion criteria for the study. The overall prevalence of hypertension in the study population was 24%. Hypertension rates were 52%, 41%, 27%, and 20% in 25-hydroxyvitamin D quartiles <15 ng/mL, 15 to 29 ng/mL, 30 to 39 ng/mL, and ≥40 ng/mL, respectively (P<.001). Odds ratios (95% confidence intervals) for hypertension adjusting for age, sex, race, and renal insufficiency were 2.7 (1.4-5.2), 2.0 (1.5-2.6), and 1.3 (1.2-1.6) for 25-hydroxyvitamin D levels <15 ng/mL, 15 to 29 ng/mL, and 30 to 39 ng/mL, respectively, compared with the ≥40 ng/mL group. This study demonstrates increased rates of hypertension in individuals who tested for lower levels of 25-hydroxyvitamin D starting at levels <40 ng/mL. This retrospective analysis raises the question of whether supplementing to optimal vitamin D levels can prevent or improve hypertension.

Abstract: According to the Barker hypothesis, intrauterine growth restriction and premature delivery adversely affect cardiovascular health in adult life. The association of childhood hypertension as a cardiovascular risk factor and birth weight has been understudied. In a prospective cohort study, the authors evaluated the effect of birth weight, gestational age, maternal prepregnancy body mass index (BMI), and child BMI z score at the time of enrollment on the systolic and diastolic blood pressure (BP) z score in 3024 (1373 women) consecutive outpatient clinic patients aged 2.05 to 18.58 years. The latest National Health and Nutrition Examination Survey (NHANES III) was used to calculate the age-dependent z scores. The median z scores of BMI (+0.48, range -6.96-6.64), systolic BP (+0.41, range -4.50-6.73), and diastolic BP (+0.34, range -3.15-+6.73) were all significantly greater than the NHANES III reference population. Systolic BP z score did not correlate with birth weight or gestational age, but did correlate with maternal prepregnancy BMI (r=.090, P<.0001) and BMI z score (r=.209, P<.0001). Diastolic BP z score positively correlated with birth weight (0.037, P=.044), gestational age (r=.052, P=.005), BMI z score(r=.106, P<.0001), and maternal prepregnancy BMI (r=.062, P=.0007). In contrast to what would be expected from the Barker hypothesis, the authors found no negative correlation between BP z score and birth weight or gestational age. This study suggests that a high BMI, a big mom, and a high birth weight are more important risk factors for hypertension during childhood than low birth weight or gestational age.

Abstract: Hypertensive disorders of pregnancy (HDP), including pre-existing hypertension, gestational hypertension, and preeclampsia, further complicate already high-risk pregnancies in women with diabetes mellitus (DM). Women with both pre-existing and gestational diabetes are at increased risk for HDP, leading to higher maternal and fetal morbidity. Further, particularly in diabetic women and women with a history of gestational diabetes, HDP significantly increases the risk for future cardiovascular events. For clinicians, women with hypertension and diabetes during pregnancy pose a management challenge. Specifically, preconception management should stress strict control of glycemia, blood pressure, and prevention of diabetic complications, specifically nephropathy, which specifically increases the risk for preeclampsia. During gestation, clinicians must be aware of potential maternal and fetal complications associated with various anti-hypertensive therapies, including known fetotoxicity of ACE inhibitors and ARBs when given in the 2nd or 3rd trimester, and the risks and benefits of expectant management versus delivery in cases of severe gestational hypertension or preeclampsia. Indeed, diabetic women must be followed closely prior to conception and throughout gestation to minimize the risk of HDP and its associated complications.

Abstract: Despite the availability of many effective antihypertensive drugs, the drug therapy for resistant hypertension remains a prominent problem Reviews offer only the general recommendations of increasing dosage and adding drugs, offering clinicians little guidance with respect to the specifics of selecting medications and dosages A simplified decision tree for drug selection that would be effective in most cases is needed This review proposes such an approach The approach is mechanism-based, targeting treatment at three hypertensive mechanisms: (1) sodium/volume, (2) the renin-angiotensin system (RAS), and (3) the sympathetic nervous system (SNS) It assumes baseline treatment with a 2-drug combination directed at sodium/volume and the RAS and recommends proceeding with one or both of just two treatment options: (1) strengthening the diuretic regimen, possibly with the addition of spironolactone, and/or (2) adding agents directed at the SNS, usually a β-blocker or combination of an α- and a β-blocker The review calls for greater research and clinical attention directed to: (1) assessment of clinical clues that can help direct treatment toward either sodium/volume or the SNS, (2) increased recognition of the role of neurogenic (SNS-mediated) hypertension in resistant hypertension, (3) increased recognition of the effective but underutilized combination of α- + β-blockade, and (4) drug pharmacokinetics and dosing

Abstract: J Clin Hypertens (Greenwich). 2011;13:716–721. ©2011 Wiley Periodicals, Inc. Serum calcium levels have been shown to be associated with cardiovascular disease (CVD); however, it is not clear whether serum calcium levels are related to hypertension, a risk factor for CVD. The authors examined the association between serum calcium and hypertension in a representative sample of US adults. A cross-sectional study of 12,405 third National Health and Nutrition Examination Survey participants 20 years and older was conducted. Serum total and ionized calcium levels were analyzed as quartiles. The main outcome of interest was hypertension (n=3437), defined as self-reported use of antihypertensive medication and/or systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Elevated serum total calcium levels were positively associated with hypertension, independent of potential confounders including C-reactive protein, estimated glomerular filtration rate, serum albumin, 25(OH)D, and phosphorous. Compared with the lowest quartile of serum total calcium (referent category), the multivariable odds ratio (95% confidence interval) of hypertension was 1.49 (1.15–1.93) for the highest quartile (P=.005). This association persisted in subgroup analyses stratified by sex, age, and race-ethnicity. In contrast, serum ionized calcium levels were not associated with hypertension. Higher serum total calcium levels are positively associated with hypertension in a representative sample of US adults.

Abstract: KEY POINTS AND PRACTICAL RECOMMENDATIONS: • Hydralazine and minoxidil act by dilating resistance arterioles, thus reducing peripheral resistance, with no dilating effect on the venous side of the circulation. • There is a baroreflex-mediated venoconstriction, resulting in an increase in venous return to the heart, along with a direct catecholamine-mediated positive inotropic and chronotropic stimulation of the heart. • Hydralazine therapy is usually combined with a sympathetic inhibitor to prevent expression of this reflex, as well as with a diuretic agent to prevent sodium retention caused by reduction in renal perfusion pressure. • Hydralazine is indicated in the long-term therapy of essential hypertension, in the short-term therapy of pregnancy-induced hypertension and eclampsia, and in the therapy of hypertensive crisis. • Adverse effects include the anticipated tachycardia, fluid retention, and headache, caused by the vasodilation, especially in the early days of therapy, but may frequently be prevented by the concomitant use of a β-blocker. • As with other drugs that are N-acetylated, there is a low risk of lupus-like syndrome with high doses and long-term use. • Because of the severity of adverse effects with minoxidil, its usage is limited to persons with severe hypertension unresponsive to other treatments. • Hirsutism, a common side effect of minoxidil, is particularly bothersome in women and reverses in a few months after discontinuation. • Sodium nitroprusside is used in the intensive care setting to lower pressure in hypertensive crisis or to treat severe left ventricular failure, particularly valuable when elevated pressure or severe left ventricular failure threatens the patient's survival. • Although nitrates have not achieved widespread use as antihypertensive agents, they are effective in producing sustained blood pressure (BP) reductions when added to other antihypertensive regimens.

Abstract: The effectiveness and safety of valsartan have not been assessed in hypertensive children. Therefore, hypertensive patients aged 6 to 16 years (n=261) were randomized to receive weight-stratified low- (10/20 mg), medium- (40/80 mg), or high-dose (80/160 mg) valsartan for 2 weeks. After 2 weeks, patients were randomized to a 2-week placebo-controlled withdrawal phase. Dose-dependent reductions in sitting systolic blood pressure (SSBP) and sitting diastolic blood pressure (SDBP) were observed after 2 weeks (low dose, -7.9/-4.6 mm Hg; medium dose, -9.6/-5.8 mm Hg; high dose, -11.5/-7.4 mm Hg [P<.0001 for all groups]). During the withdrawal phase, SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group (SSBP, -2.7 mm Hg [P=.0368]; SDBP, -3.0 mm Hg [P=.0047]). Similar efficacy was observed in all subgroups. Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double-blind and 52-week open-label phases.

Abstract: Despite improvements in blood pressure (BP) control, a substantial percentage of patients do not achieve target. The relative importance of determinants of poor BP control is unclear. Therefore, the authors conducted a post hoc exploratory analysis to assess determinants of BP control. Data were collected in 45 general practices, which enrolled patients with uncontrolled hypertension. Antihypertensive medication changes throughout the 6-month follow-up period were documented. Baseline and 6-month BPs were recorded. Of the 2030 patients analyzed, 320 had diabetes. Overall, 42% of patients did not achieve BP control. In multivariate analysis, failure to intensify therapy was identified as a significant independent predictor of lesser BP reduction. Of patients unable to reach target after 6 months, only 25% were prescribed ≥ 3 drugs. Patients with diabetes were significantly less likely to reach target than those without (26% vs 64%, P<.001). Antihypertensive therapy prescribed to patients with diabetes was only marginally more intensive than to those without. In patients with hypertension, whether with or without coexisting diabetes, poor BP control appears to be at least partially due to failure to uptitrate antihypertensive therapy. Clinical inertia is likely an important barrier to BP control.

Abstract: Patients' knowledge concerning high blood pressure (HBP) is a useful outcome measure in HBP education programs. However, valid and easy-to-use HBP knowledge assessment tools are scarce. The purpose of the study was to validate the High blood pressure Knowledge Test (HKT) in two independent samples of Korean Americans with HBP (N=885); 61% women; mean age about 61 years (SD=11.0); 44% some college education or greater. Psychometric and item response theory analyses identified 21 items fitting a unidimensional model to form the HKT. Internal consistency was acceptable: Cronbach's alpha=0.70. Construct validity testing revealed that those with controlled BP had significantly higher HKT scores than those with uncontrolled BP (p=.012). The HKT is a simple questionnaire for assessing and monitoring HBP knowledge. It is sensitive to differences in BP control status and should provide a valid, reliable and standardized measure of HBP knowledge with wide relevance.

Abstract: This 12-week, multicenter, randomized, double-blinded, 4-arm study in 440 patients with moderate to severe hypertension compared ambulatory blood pressure (ABP) responses with a triple-combination regimen (olmesartan medoxomil [OM] 40 mg, amlodipine besylate [AML] 10 mg, and hydrochlorothiazide [HCTZ] 25 mg) and its component dual-combination regimens at similar doses. At week 12, the triple combination resulted in a greater reduction in mean 24-hour systolic and diastolic blood pressure (-30.3/-18.0 mm Hg) compared with the 3 dual-combination regimens (OM 40 mg/AML 10 mg: -23.5/-13.9, OM 40 mg/HCTZ 25 mg: -23.9/-14.5, and AML 10 mg/HCTZ 25 mg: -18.5 mm Hg/-10.7 mm Hg; P<.0001 each). Greater efficacy was also found during daytime and nighttime hours and during the last 6, 4, or 2 hours of the dosing interval. The authors conclude that the triple combination of OM 40 mg/AML 10 mg/HCTZ 25 mg demonstrated superior efficacy and sustained reductions in ABP compared with its dual-combination components.

Abstract: Intravascular ultrasound (IVUS) is a novel technique that provides an accurate and reproducible method to measure atheroma burden. Statin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. Studies assessing the effect of statin treatment on atheroma burden have shown conflicting results. Hence, this meta-analysis was conducted to evaluate the impact of statin therapy on coronary atherosclerosis progression. A systematic search using PubMed, EMBASE, and Cochrane Library databases was performed. Heterogeneity of the studies was analyzed by Cochran's Q statistics. The significance of common treatment effect was assessed by computing common mean difference between the control and treatment groups. A two-sided α error of <0.05 was considered statistically significant (P<.05). Eight trials composed of 919 patients including a placebo group with 458 patients and a treatment group with 461 patients were used. Characteristics of both groups at baseline were similar without any significant difference between them. In the pooled analysis, the common mean difference of coronary atheroma volume between statin therapy and the placebo arm was -3.573 (confidence interval, -4.46 to -2.68; P<.01). This meta-analysis demonstrates that treatment with statins not only slows atherosclerotic plaque progression but may also lead to plaque regression.