Health Questions and Answers

Hypertension

A 47-year-old hypertensive man has been treated with amlodipine 10 mg/day orally, for chronic stable angina pectoris and hypertension. He complains of ankle edema that worsened after her dose of amlodipine was recently increased. Are diuretics indicated?
Ankle edema is a common side effect of dihydropyridine calcium channel blockers, occurring in 7-20% of patients treated. It is a dose-dependent side effect and readily responds to down-titration of the calcium channel blocker dose. Another novel strategy to minimize the occurrence of this ankle edema is to combine calcium channel blockade with ACE inhibition. This combination is more effective than monotherapy with either drug in lowering blood pressure and is associated with lower prevalence of any dose-related side effects, including ankle edema.

Prehypertension
Data from the Framingham cohort indicate that blood pressure bears a linear relationship with cardiovascular risk down to a systolic blood pressure of 115 mm Hg; based on these data, it is recommended that individuals with blood pressures in the gray area of 120–139/80–89 mm Hg be categorized as having prehypertension. This demonstrates a trend away from defining hypertension as a simple numerical threshold and toward a more subtle appreciation of blood pressure as a component of overall cardiovascular risk. This trend gains support from increasing evidence for a relationship between blood pressure and disruption of cardiovascular function at levels below the hypertensive threshold. Because prehypertension often develops into hypertension (50% of people within 4 years), even low-risk prehypertensive patients should be monitored annually. Circumspection about labeling patients as hypertensive is warranted since there is evidence that simply telling someone that he or she has hypertension has unintended consequences, transforming a perception of general health into one of general ill-health.

How do you classify or stage HTN severity? Is this classification practically useful in your approach to antihypertensive drug therapy?
HTN is now classified into two stages, depending on whether BP is > 160/100 mmHg. Patients with stage 2 HTN (BP >1 60/100 mmHg) are rarely controlled to a goal BP of < 140/90 mmHg on a single BP-lowering drug. In fact, the ALLHAT trial as well as several other trials have shown that at least two or more drugs are needed in two thirds of hypertensives; in one third of hypertensive patients, three BP-lowering drugs may be needed to get BP to goal.

What are current guidelines for treatment of HTN?
To maximize BP control, the current guidelines recommend routine initiation of two BP-lowering drugs in patients with stage 2 HTN. This combination can include any of the following classes of antihypertensive drugs: thiazide diuretics, beta blockers, ACE inhibitors, or calcium channel blockers. Since thiazide diuretics are readily available, inexpensive, and as effective as calcium channel blockers or beta blockers in reducing cardiovascular complications of hypertension, they are generally recommended as an important part of any antihypertensive drug regimen. However, the selection of a specific antihypertensive drug class should take into consideration comorbid conditions associated with HTN, such as diabetes mellitus, heart failure, CAD, or renal failure as well as the patient’s tolerance of specific drug classes.

Describe your approach to the initial evaluation of a patient with possible secondary causes of HTN. What is the value of findings such as postural HTN, paroxysmal HTN, and hypokalemia in the diagnostic work-up of such patients?
The initial evaluation of the hypertensive patient should be focused on historical or physical clues to the various causes of secondary HTN, including:

  1. Alcohol consumption
  2. Muscle weakness
  3. Headache
  4. Nervousness
  5. History of renal parenchymal disease
  6. Documented postural hypotension
  7. Dietary salt intake
  8. Paroxysmal episodes of palpitation
  9. Sweating
  10. Nausea or vomiting
  11. Concomitant history of generalized atherosclerotic vascular disease

A careful history (including age at onset of HTN and family history of HTN), physical examination, laboratory panel (urinalysis, microscopy, complete blood cell count, blood electrolytes, serum creatinine), chest x-ray, and 12-lead ECG should be obtained in all patients evaluated for HTN.

What do paroxysmal and postural HTN suggest?
Pheochromocytoma.

Which findings suggest renal artery stenosis?

Generalized atherosclerosis and abdominal or flank bruits.

What do muscle weakness and unexplained hypokalemia suggest?
Aldosteronism.

Which findings suggest parenchymal renal disease?

Prior history of renal parenchymal disease and the presence of abnormal urine sediment suggest secondary HTN due to parenchymal renal disease.

It is generally accepted that antihypertensive therapy lowers the risk of stroke, but does it have any effect on risk of MI and angina?
The Systolic Hypertension in the Elderly Program (SHEP) demonstrated that a thiazide-based antihypertensive regimen (chlorthalidone, 12.5-25 mg/day, alone or combined with atenolol, 25-50 mg/day) reduces stroke risk by 36% and nonfatal MI plus coronary death by 27% in older (> 60 yr) patients with isolated systolic HTN (systolic BP > 160 mmHg/diastolic BP < 90 mmHg). Major cardiovascular events were reduced by 32%. As a result, overall all-cause mortality was 13% lower. Similar studies in younger hypertensive patients have shown a smaller beneficial effect or no effect of antihypertensive drug therapy on CAD events.

Are calcium blockers as effective as diuretics in isolated systolic hypertension?
A similarly designed multicenter clinical trial, the Systolic Hypertension in Europe (Syst-Eur) Trial, showed the same reduction in cardiac and stroke events in older (>60 yr) patients with systolic HTN (systolic BP > 160 mm Hg) and normal or mildly elevated diastolic BP (< 95 mm Hg) with a long-acting dihydropyridine calcium blocker, alone or in combination with an ACE inhibitor. The SHEP and Syst-Eur trials confirm a significant beneficial reduction in coronary heart disease (CHD) as well as stroke from lowering systolic BP in patients with isolated systolic HTN with either a diuretic or dihydropyridine calcium blocker-based therapy.

What are the complications of untreated Hypertension?
Complications of hypertension are related either to sustained elevations of blood pressure, with consequent changes in the vasculature and heart, or to atherosclerosis that accompanies and is accelerated by long-standing hypertension. Most of the adverse outcomes in hypertension are associated with thrombosis rather than bleeding, possibly because increased vascular shear stress converts the normally anticoagulant endothelium to a prothrombotic state. The excess morbidity and mortality related to hypertension are progressive over the whole range of systolic and diastolic blood pressures; the risk approximately doubles for each 6 mm Hg increase in diastolic blood pressure. However, target-organ damage varies markedly between individuals with similar levels of office hypertension; ambulatory pressures are superior to office readings in the prediction of end-organ damage.

  1. Hypertensive Cardiovascular Disease- Cardiac complications are the major causes of morbidity and mortality in primary (essential) hypertension, and preventing them is a major goal of therapy. Electrocardiographic evidence of left ventricular hypertrophy is found in up to 15% of persons with chronic hypertension. For any level of blood pressure, its presence is associated with incremental cardiovascular risk. Echocardiographic left ventricular hypertrophy is a powerful predictor of prognosis. Left ventricular hypertrophy may cause or facilitate many cardiac complications of hypertension, including congestive heart failure, ventricular arrhythmias, myocardial ischemia, and sudden death. Left ventricular diastolic dysfunction, which may present with all of the symptoms and signs of congestive heart failure, is common in patients with long-standing hypertension. The occurrence of heart failure is reduced by 50% with antihypertensive therapy. Hypertensive left ventricular hypertrophy regresses with therapy and is most closely related to the degree of systolic blood pressure reduction. Diuretics have produced equal or greater reductions of left ventricular mass when compared with other drug classes. -Blockers are less effective in reducing left ventricular hypertrophy but play a specific role in patients with established coronary artery disease or impaired left ventricular function.
  2. Hypertensive Cerebrovascular Disease and Dementia- Hypertension is the major predisposing cause of hemorrhagic and ischemic stroke. Cerebrovascular complications are more closely correlated with systolic than diastolic blood pressure. The incidence of these complications is markedly reduced by antihypertensive therapy. Preceding hypertension is associated with a higher incidence of subsequent dementia of both vascular and Alzheimer types. Effective blood pressure control may reduce the risk of development of cognitive dysfunction later in life, but once cerebral small vessel disease is established, low blood pressure might exacerbate this problem.
  3. Hypertensive Renal Disease- Chronic hypertension leads to nephrosclerosis, a common cause of renal insufficiency; aggressive blood pressure control attenuates the process. In patients with hypertensive nephropathy, the blood pressure should be 130/80 mm Hg or lower, especially when proteinuria is present. Secondary renal disease is more common in blacks, particularly when accompanied by diabetes mellitus. Hypertension also plays an important role in accelerating the progression of all forms of renal disease.
  4. Aortic Dissection- Hypertension is a contributing factor in many patients with dissection of the aorta.
  5. Atherosclerotic Complications- Most Americans with hypertension die of complications of atherosclerosis, but the link between hypertension and atherosclerotic cardiovascular disease is not as clear as that with the previously discussed complications. Effective antihypertensive therapy is thus less successful in preventing complications of coronary heart disease.

A 42-year-old woman has an office BP reading of 150/90 mmHg. Should you initiate antihypertensive therapy?
Initiation of chronic antihypertensive drug therapy in a patient with a single office BP measurement of 150/90 mmHg is not recommended. Unlike diastolic BP, systolic BP is subject to wider variations between office visits and even between examiners during a single office visit.

What factors may affect systolic BP measurements and lead to an erroneous diagnosis of systemic HTN?

  • Patient’s anxiety level
  • Ambient temperature at the doctor’s office
  • Examiner (physician or nurse)
  • Time of day
  • Physical activity preceding BP measurement
  • Size of cuff used
  • Patient’s posture (supine, sitting, or standing)
  • Coexistent medical problems (e.g., fever, thyrotoxicosis, anemia, AV fistula)

How many BP measurements are needed to initiate antihypertensive therapy?
Drug therapy for hypertension is generally recommended for sustained elevations of sitting BP exceeding 140/90 mmHg during at least two clinic visits. The exceptions are diabetics and patients with chronic renal disease, for whom antihypertensive drug therapy is recommended at a BP of 130/80 or higher.

Which antihypertensive drug classes are currently recommended as first-line drugs in the treatment of HTN in patients at high risk for CHD?
Four classes of antihypertensive drugs are recommended as first-line therapy in hypertensive patients at high risk for CHD because of associated risk factors such as old age, dyslipidemia, diabetes, or smoking history:

  • Thiazide diuretics
  • Beta blockers
  • Calcium blockers
  • ACE inhibitors

All of these drugs have now been conclusively demonstrated to reduce the incidence of stroke and CHD in high-risk, predominantly older hypertensive patients.

What classes of antihypertensive drugs are preferred for use in a patient with a known history of CHF? Which drugs should you avoid?

  1. Vasodilators: direct vascular smooth muscle-relaxing drugs (hydralazine and minoxidil)
  2. ACE inhibitors (captopril, enalapril, lisinopril, ramipril or monopril)
  3. Angiotensin receptor blockers (losartan, irbesartan, valsartan, candesartan, telmisartan)
  4. Diuretics, such as thiazide diuretics (hydrochlorothiazide)

KEY POINTS: HYPERTENSION

  1. If blood pressure is > 160/100 mmHg, start two antihypertensive drugs to maximize control of HTN and prevention of hypertensive complications.
  2. Systolic blood pressure is the more powerful and more consistent predictor of heart disease, stroke, and end-stage renal disease.
  3. Thiazide diuretics and amlodipine are equally effective in preventing cardiovascular complications of HTN in patients who are at high risk for CHD and older than 55 yr.
  4. Both thiazide diuretics and amlodipine are more effective than an ACE inhibitor as first-line antihypertensive therapy, particularly in older people and/or African Americans.

Which drugs should be avoided in patients with a known history of CHF?
Drugs with negative inotropic effects should be avoided:

  • Calcium blockers of the nondihydropyridine class (verapamil, diltiazem)
  • Beta blockers (e.g., propranolol, metoprolol, atenolol)

Are all calcium blockers contraindicated in patients with heart failure?
No. Amlodipine, a dihydropyridine calcium blocker with no clinically significant negative inotropic effects, has been extensively evaluated in two large, prospective, placebo-controlled clinical trials in patients with heart failure. Unlike nondihydropyridine calcium blockers, amlodipine can be used safely in patients with impaired systolic function who have an indication for the use of a calcium blocker, such as HTN or angina pectoris.

Do beta blockers ever have a role in patients with heart failure?
Although beta blockers are generally considered to be contraindicated in patients with heart failure, an increasing number of clinical trials with beta blockers such as carvedilol and metoprolol- carefully and gradually titrated starting with very low doses-support a beneficial long-term effect in patients of New York Heart Association (NYHA) functional class II and III (mild-to-moderate symptomatic heart failure). The initiation of beta blockers even in low doses in patients with heart failure should be done very cautiously as a significant proportion of these patients (as high as 30-40%) may experience symptomatic hypotension or worsening heart failure symptoms in the first 4 weeks.

Explain the significance of the ALLHAT clinical trial.
The ALLHAT trial is the largest multicenter, double-blind, controlled clinical trial designed to evaluate the effects of four different classes of antihypertensive drugs (e.g., thiazide diuretics, ACE inhibitors, alpha blockers, and calcium blockers) on CHD and stroke risk. It showed no superiority of ACE inhibitors, calcium blockers, or alpha blockers over diuretics in preventing CHD events.

Summarize the comparative results of the ALLHAT trial.

  1. CHD risk was similar in all four groups.
  2. BP control was significantly better and systolic blood pressure was 2 mmHg lower in diuretic-treated patients than in ACE inhibitor-treated patients. This difference was even higher (about 4 mmHg) in African-Americans.
  3. No difference in BP control or BP levels between diuretic- and calcium blocker-treated patients.
  4. Between 10% and 15% higher risk of stroke and CHD events in ACE inhibitor-treated compared with diuretic-treated patients. African Americans expectedly had a 40% higher stroke risk and a 19% higher CV risk compared with those treated with a diuretic; this was associated with a 4-mm higher systolic BP.

What are the two key take-home messages from ALLHAT?
Control of HTN frequently requires multiple antihypertensive drugs used in combination. The recent JNC 7 report recommends initiation of two anti-hypertensive drugs whenever BP is > 160/100 mmHg (now called stage 2 HTN).
More effective reduction of SBP (even 2 mm lower) in a high-risk older hypertensive patient results in more effective cardiovascular prevention.

Which lifestyle modifications have proved beneficial to hypertensive patients?

  • Lose weight if overweight
  • Limit alcohol intake to 1 oz/day of ethanol (24 oz of beer, 8 oz of wine, or 2 oz of 100 proof whiskey)
  • Exercise (aerobic) regularly
  • Reduce sodium intake to < 100 mmol/day (< 2.3 gm of sodium or approximately 6 gm of NaCl)
  • Maintain adequate dietary potassium, calcium, and magnesium intake
  • Stop smoking
  • Reduce dietary saturated fat and cholesterol intake for overall cardiovascular health (reducing fat intake also helps reduce caloric intake, which is important for control of weight and type II diabetes)

Last Updated May 12,  2010

References
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