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Hypertension is a mechanism-based toxic effect of drugs that inhibit the vascular endothelial growth factor signaling pathway (VSP). Substantial evidence exists for managing hypertension as a chronic condition, but there are few prospectively collected data on managing acute hypertension caused by VSP inhibitors. The Investigational Drug Steering Committee of the National Cancer Institute convened an interdisciplinary cardiovascular toxicities expert panel to evaluate this problem, to make recommendations to the Cancer Therapy Evaluation Program on further study, and to structure an approach for safe management by treating physicians. The panel reviewed: the published literature on blood pressure (BP), hypertension, and specific VSP inhibitors; abstracts from major meetings; shared experience with the development of VSP inhibitors; and established principles of hypertension care. The panel generated a consensus report including the recommendations on clinical concerns summarized here. To support the greatest possible number of patients to receive VSP inhibitors safely and effectively, the panel had four recommendations: 1) conduct and document a formal risk assessment for potential cardiovascular complications, 2) recognize that preexisting hypertension will be common in cancer patients and should be identified and addressed before initiation of VSP inhibitor therapy, 3) actively monitor BP throughout treatment with more frequent assessments during the first cycle of treatment, and 4) manage BP with a goal of less than 140/90 mmHg for most patients (and to lower, prespecified goals in patients with specific preexisting cardiovascular risk factors). Proper agent selection, dosing, and scheduling of follow-up should enable maintaining VSP inhibition while avoiding the complications associated with excessive or prolonged elevation in BP. DOI: 10.1093/jnci/djq091

OBJECTIVE--Optimal initial antihypertensive drug therapy in people with the metabolic syndrome is unknown. RESEARCH DESIGN AND METHODS--We conducted a subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart [...]

One of the most common medical conditions in the United Sates, hypertension affects 24% of American adults.[1] Despite the numerous therapeutic options, control rates for hypertension in this country have [...]

Background: Garlic powder tablets have been reported to lower serum cholesterol levels. There is widespread belief among the general public that garlic powder tablets aid in controlling cholesterol levels. However. much of the prior data demonstrating the cholesterol-lowering effect of garlic tablets involved studies that were inadequately controlled. Objectives: To determine the lipid-lowering effect of garlic powder tablets in patients with hypercholesterolemia. Methods: This was a randomized, double-blind, placebo-controlled, 12-week, parallel treatment study carried out in 2 outpatient lipid clinics. Entry into the study after 8 weeks of diet stabilization required a mean low-density lipoprotein cholesterol level on 2 visits of 4.1 mmol/L (160 mg/dL) or lower and a triglyceride level of 4.0 mmol/L (350 mg/dL) or lower. The active treatment arm received tablets containing 300 mg of garlic powder (Kwai) 3 times per day, given with meals (total, 900 mg/d). This is equivalent to approximately 2.7 g or approximately 1 clove of fresh garlic per day. The placebo arm received an identical-looking tablet, also given 3 times per day with meals I The main outcome measures included levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol after 12 weeks of treatment. Results: Twenty-eight patients (43% male; mean [+ or -] SD age, 58 [+ or -] 14 years) received garlic powder treatment and 22 (68% male, mean [+ or -] SD age, 57 [+ or -] 13 years) received placebo treatment. There were no significant lipid or lipoprotein changes in either the placebo- or garlic-treated groups and no significant difference between changes in the placebo-treated group compared with changes in the garlic-treated patients. Conclusions: Garlic powder (900 mg/d) treatment for 12 weeks was ineffective in lowering cholesterol levels in patients with hypercholesterolemia. Arch Intern Med. 1998;158:1189-1194

Background: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and [Beta]-blockers adversely alters levels of other cardiovascular disease risk factors. Methods: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. Results: After 3 years, the active treatment group had a 13/4 min Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P [is less than] 001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P = .25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P [is less than] 01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P [is less than] .01), high-density lipoprotein cholesterol (0.02 mmol/L [-0.77 mg/dL]; P [is less than] 01) and creatinine (+2.8 [micro]mol/L [+0.03 mg/dL]; P [is less than] 001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P [is less than] 001), uric acid (+35 [micro]mol/L [+.06 mg/dL]; P [is less than] 001), and potassium (-0.3 mmol/L; P [is less than] 001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. Conclusions: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels. Arch Intern Med. 1998;158:741-751

Modern antihypertensive regimens control blood pressure in the majority of patients. What about the rest? If you can rule out secondary hypertension, poor compliance, and too much salt, consider refractory [...]

One of the current recommendations for the treatment of hypertension is a stepped-care approach in which a second drug is added to a first-line agent when adequate blood pressure control has not been achieved. It has been well demonstrated in multiple studies that the response rate to any single class of antihypertensive agent, given as monotherapy, is approximately 45-55%. Thus, in approximately half of the hypertensive population, a second drug will be required. This is not surprising, since it is now well recognized that hypertension is a multifaceted disease process. The use of combination therapy with low-dose diuretics (

Safe and effective antihypertensive therapy became available in the 1950s with the introduction of thiazide diuretics. Prior to that time, we did have agents that lowered blood pressure but they often needed to be given parenterally and were too poorly tolerated to be used for the treatment of any but those with life-threatening elevations of blood pressure. When thiazide diuretics - first chlorothiazide and then hydrochlorothiazide - became available, it was possible to lower blood pressure in most hypertensives and assess whether that reduction would lead to a reduction in cardiovascular morbidity and mortality. The results of 17 large trials have now made it clear that antihypertensive therapy with regimens based on diuretics and [Beta] blockers reduces cardiovascular events and saves lives. When first introduced, thiazide diuretics were prescribed at doses we now know are excessively high (100-200 mg of hydrochlorothiazide/day), and we have learned that much lower doses, even as little as 12.5 mg of hydrochlorothiazide, are effective. These lower doses will reduce blood pressure and do so with considerably less in the way of metabolic effects. This article will trace the development of antihypertensive therapy and review how data from clinical trials have influenced the recommendations of the Joint National Committees on the Detection, Evaluation and Treatment of Hypertension.

The highest prevalence of hypertension is now recognized to exist in the elderly segment of the population. With the completion of several large-scale studies, several of our assumptions regarding elderly hypertensive patients have changed. It is now clear that the elderly have shown the greatest benefit from antihypertensive therapy. This favorable risk--benefit ratio extends to even the very elderly; treatment for hypertension is appropriate for healthy elderly individuals, regardless of age. It also extends to elderly individuals who have already experienced the consequences of elevated blood pressure. Attitudes toward antihypertensive agents have also evolved. Diuretics are appropriate monotherapy in many patients, when the dose is kept low. The usefulness of calcium antagonists has been confirmed, whereas [beta] blocker use appears to be indicated only in certain subgroups. Recently, angiotensin-converting enzyme inhibitors have also been shown to be effective in elderly patients, despite earlier studies whose results describe low plasma renin activity in the elderly.

Study Objective. -- To determine the prevalence of resistant hypertension in a tertiary care facility, the frequency of its various causes, and the results of treatment. Design. -- Review of clinic records of all patients seen for the first time between January 1, 1986, and December 31, 1988. Methods. -- Patients meeting criteria for resistant hypertension were examined for appropriateness of their medical regimen, presence of secondary causes of hypertension, noncompliance, interfering substances, drug interactions, office resistance (elevated blood pressure in the office only while receiving treatment), and other potential causes of resistance. Results.-- Of the 436 charts reviewed, 91 were those of patients who met criteria for resistant hypertension and were seen more than once. The most common cause was a suboptimal medical regimen (39 patients), followed by medication intolerance (13 patients), previously undiagnosed secondary hypertension (10 patients), noncompliance (nine patients), psychiatric causes (seven patients), office resistance (two patients), an interfering substance (two patients), and drug interaction (one patient). Blood pressure control, defined as diastolic blood pressure of 90 mm Hg or less and systolic blood pressure of 140 mm Hg or less for patients aged 50 years or less ([is less than or equal to] 150 mm Hg for those aged 51 to 60 years and [is less than or equal to] 1 mm Hg for those aged >60 years), was achieved in 48 (53%) of those 91 patients. Another 10 had significant improvement in their blood pressure [is greater than or equal to] 15% decrease in diastolic blood pressure). Of patients whose blood pressure was controlled after they had been on a suboptimal regimen, the two most frequently used therapeutic strategies were to add (50%) or modify (24%) diuretic therapy or to add (50%) or increase the dose of (12%) a newer drug, either a calcium entry blocker or angiotensin-converting enzyme inhibitor. Conclusion.-- We conclude that resistant hypertension is common in a tertiary care facility and that a suboptimal regimen is the most common reason. Furthermore, in the majority of these patients, the elevated blood pressures can be controlled or significantly improved. (Arch Intern Med 1991;151:1786-1792)

Patients with high blood pressure (hypertension) are classified by the level of diastolic blood pressure (the lower of two numbers in a blood pressure reading, indicating pressure as the heartbeat enters the rest phase). However, systolic blood pressure (the higher number, corresponding to the contraction phase) is a better predictor of outcome among these patients. Not all hypertensive patients have the same level of risk. Those who smoke are far more likely to develop cardiovascular disease. Those with coronary artery or cerebrovascular disease, kidney dysfunction, or enlargement (hypertrophy) of the left ventricle (LV) will also do worse. LV hypertrophy has been shown to be a major risk factor in several studies. LV hypertrophy is usually diagnosed by electrocardiogram, which is noninvasive, easy to do, portable, relatively inexpensive, and most physicians can interpret its results. However, LV enlargement is often missed by electrocardiography. Several of the newer imaging techniques, especially echocardiography, which uses ultrasound, do provide direct, reliable measures of LV mass and volumes. Echocardiography is widely available, safe, easy, and can be done repeatedly. It also offers a way to quantify the thickness of the muscle wall, providing a means of measuring the effects of treatment. The Joint National Committee on the Detection, Evaluation and Treatment of Hypertension agreed that echocardiography was better than electrocardiography for evaluating LV mass, but did not recommend it because of concerns about reliability and cost. The reliability issue has been addressed, but the cost remains high. However, a limited echocardiogram has been developed specifically to measure LV mass, at one third to one half the cost of a full echocardiographic examination. The question is whether this technique should be used routinely at initial and follow-up examinations of hypertensive patients. It is appropriate to individualize evaluation of hypertensive patients, just as therapy has been individualized. (Consumer Summary produced by Reliance Medical Information, Inc.)

Congestive heart failure (CHF) is a condition in which the left side of the heart does not supply sufficient blood to the body, resulting in shortness of breath, weakness, and sometimes death. It is often caused by the inability of the left ventricle to pump blood, but in a significant number of cases (30 to 40 percent), left ventricular function is normal. In these patients CHF is thought to result from impaired diastolic filling (blood does not fill the ventricle of the heart in an appropriate fashion during the period of cardiac relaxation). Treatment for this group of patients has not been defined, but it has been reported that calcium antagonists have a beneficial effect in CHF patients with normal left ventricular function. (Calcium antagonists induce dilation of blood vessels by preventing the entry of calcium into muscle fibers, resulting in their relaxation.) To further evaluate this, a group of 20 men (average age 68 years) with congestive heart failure, normal left ventricular function (as measured by ejection fraction, or the percentage of blood pumped during maximal contraction), and abnormal diastolic filling were treated for five weeks with either placebo or the calcium antagonist verapamil. At the end of treatment, the verapamil-treated patients showed a significant improvement in exercise capacity (33 percent) and ventricular filling rate (30 percent increase), compared with their test results during the pretreatment period. Placebo-treated controls did not show significant increases in either parameter. Verapamil caused an increase in a global index of cardiac function. Ejection fraction and blood pressure were unchanged by either placebo or verapamil treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Renovascular hypertension, or blood pressure elevation caused by vascular disease of the kidneys, can be treated by improving blood flow to the kidneys by either surgical or angioplasty revascularization. Identification of patients who will benefit from revascularization is difficult. Captopril, an angiotensin converting enzyme inhibitor, can temporarily reduce kidney function in patients with renal artery disease, and this decrease in function can be measured by using nuclear medicine scanning scintigraphy (measuring tissue density). Captopril renal scintigraphy (CRS) can identify renal artery stenosis (narrowing) as well as disease occurring in only one kidney. Consequently, this technique can be used to identify those patients who are most likely to benefit from revascularization. The ability of CRS to predict the outcome of renal artery revascularization surgery was evaluated. Seventy patients with suspected renovascular hypertension were examined first with a renal scan, followed by CRS; 19 patients had abnormal renal scan findings, and 17 had decreased flow or kidney function after captopril. Of these 17 patients, 8 who had captopril-induced changes in renograms were selected for revascularization on the basis of clinical and imaging criteria; 6 patients were cured or experienced improvement of their hypertension. Seven patients had abnormal renal scans, but normal CRS; only one patient improved following treatment (nephrectomy) for hypertension. These results demonstrate that CRS is able to accurately predict the patient's hypertensive response to revascularization procedures. (Consumer Summary produced by Reliance Medical Information, Inc.)

CASE A 47-year-old white woman with a history of aortic stenosis secondary to a congenital bicuspid aortic valve develops hypertension of unknown origin. In 1977, she received a porcine aortic [...]

* To assess the prevalence of cough as a side effect of angiotensin-converting enzyme inhibitor antihypertensive therapy, we reviewed 300 consecutive patient charts from a private practice and 200 consecutive patient charts from a university-based referral center for hypertension. Incidence of definite angiotensin-converting enzyme inhibitor-induced cough in the private practice was 25% and in the university practice, 7%, with an additional 6% of university-practice patients reporting a possible angiotensin-converting enzyme-inhibitor induced cough. This incidence is considerably greater than listed in the Physicians' Desk Reference. Reasons for the variability in incidence as reported in the literature are explored. Clinicians must be aware of this potentially disturbing side effect of angiotensin-converting enzyme inhibitors to avoid expensive and unnecessary diagnostic evaluations. (Arch Intern Med. 1992;152:1698-1700)

Background: The recommendation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) to lower blood pressure (BP) in diabetic patients to less than 130/85 mm Hg may have negative economic consequences. A formal cost-effectiveness analysis was therefore performed, comparing the costs and potential benefits of a BP goal of less than 140/90 mm Hg (as recommended by JNC V) vs less than 130/85 mm Hg (as in JNC VI). Methods: A 24-cell computer model was populated with costs (1996 dollars), relative risks, and age-specific baseline rates for death and 4 nonfatal adverse events (stroke, myocardial infarction, heart failure, and end-stage renal disease), derived from published data. Costs and benefits were discounted at 3%. Results: For 60-year-old diabetic persons with hypertension, treating to the lower BP goal increases life expectancy by 0.48 (discounted) years and lowers (discounted) lifetime medical costs by $1450 compared with treating BP to less than 140/90 mm Hg. The lower treatment BP goal results in an overall cost savings over a wide range of initial conditions, and for nearly all analyses for patients older than 60 years. Conclusions: Any incremental treatment for 60-year-olds that costs less than $414 annually and successfully lowers BP from below 140/90 to below 130/85 mm Hg would be cost saving in the long term, due to the reduction in attendant costs of future morbidity. The lower treatment goal recommended for high-risk hypertensive patients compares favorably in cost-effectiveness with many other frequently recommended treatment strategies, and saves money overall for patients aged 60 years and older. Arch Intern Med. 2000;160:1277-1283

Background: There are scant data on the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) on cardiovascular events and death in older patients with hypertension. Objective: To determine if low body mass in older patients with hypertension confers an increased risk of death or stroke. Patients: Participants were 3975 men and women (mean age, 71 years) enrolled in 17 US centers in the Systolic Hypertension in the Elderly Program trial, a randomized, double-blind, placebo-controlled clinical trial of low-dose antihypertensive therapy, with follow-up for 5 years. Main Outcome Measures: Five-year adjusted mortality and stroke rates from Cox proportional hazards analyses. Results: There was no statistically significant relation of death or stroke with BMI in the placebo group (P = .47), and there was a U- or J-shaped relation in the treatment group. The J-shaped relation of death with BMI in the treated group (P = .03) showed that the lowest probability of death for men was associated with a BMI of 26.0 and for women with a BMI of 29.6; the curve was quite flat for women across a wide range of BMIs. For stroke, men and women did not differ, and the BMI nadir for both sexes combined was 29, with risk increasing steeply at BMIs below 24. Those in active treatment, however, had lower death and stroke rates compared with those taking placebo. Conclusions: Among older patients with hypertension, a wide range of BMIs was associated with a similar risk of death and stroke; a low BMI was associated with increased risk. Lean, older patients with hypertension in treatment should be monitored carefully for additional risk factors. Arch Intern Med. 2000;160:494-500

On the whole, JNC VI has been very well received, and this comes as no surprise. The report was designed to be physician-friendly; it is less dogmatic and more balanced [...]