MODULE 3 CHAPTER 2C

HYPERTENSION AND COPD

HYPERTENSION IS THE COMMONEST CO MORBID CONDITION

HYPERTENSION AND COPD Systemic hypertension is a common comorbid condition in patients with COPD, which may occur in up to 65% of patients. At present, there are no specific guidelines for the treatment of hypertension in patients with COPD. In general, the recommendations for treatment in uncomplicated hypertension may be followed in patients with COPD. However, pulmonary effects of antihypertensive agents may influence the choice.

Hypertension and COPD Systemic effects of COPD not only predisposes to hypertension but also to Cardiovascular disease COPD patient most often die of CVD rather than due to lung disease Using routine anti hypertensives also problematic in COPD because some drugs worsen COPD

SYSTEMIC MANIFESTATIONS OF COPD

% 96 % 88 % 80 % 63 % FEV 1 NHANES 1; N=1,861 RR Relationship between COPD and CVD

DRUG SELECTION

WHICH DRUG? CCBs would be the preferred antihypertensive therapy in patients with COPD, considering their potentially favorable pulmonary effects: improvement in bronchial reactivity and reduction of bronchoconstriction. Diuretics may be associated with theoretical safety concerns of worsening hypokalemia when used with β 2 -adrenergic receptor agonists and metabolic alkalosis in patients with coexisting chronic hypercapnia. ACE inhibitor use may be associated with the development of a dry cough that may exacerbate bronchial hyper responsiveness. ARBs could be used as initial therapy as their use is not associated with the dry cough seen with ACE inhibitors, but they do not exhibit the favorable respiratory effects seen with CCBs.

CCBs have been shown to be effective in lowering blood pressure in patients with COPD, and they are generally well tolerated. They may also provide additional benefits in COPD by virtue of their mechanism of action. These agents block calcium entry into smooth muscle cells, thereby causing relaxation. Thus, CCBs could oppose tracheobronchial smooth muscle contraction in COPD and reinforce the bronchodilator effect of β-agonists. Studies have shown a reduction in bronchial reactivity and bronchoconstriction in patients with COPD or asthma who are treated with CCBs. FIRST LINE CALCIUM CHANNEL BLOCKERS

WHICH IS THE SECOND DRUG? Based on the adverse effects, safety concerns, and favorable pulmonary effects of antihypertensive agents, a CCB (long-acting dihydropyridine) would be the most appropriate initial antihypertensive regimen for a patient with COPD. An ARB would be the second-best choice after the CCB.

WHAT ABOUT B BLOCKERS? β-blockers play a pivotal role in the management of cardiovascular diseases. Physicians, however, tend to underuse β-blockers in patients with COPD because there is a general perception that these agents are contraindicated in COPD patients. Considering that the majority of patients with COPD die from cardiac and not respiratory causes, the underuse of β-blockers is a significant concern.

CARDIOSELECTIVE B BLOCKERS Cardio selective β-blockers are not associated with respiratory adverse events in patients with COPD comes from a large Cochrane database review. No changes in FEV 1 or respiratory symptoms, and no effect on FEV 1 treatment response to β-2 agonists were observed in patients taking cardio selective β-blockers, irrespective of the severity of their COPD, compared with those taking placebo.

© 2005 Elsevier

COPD

DON’T BE RELUCTANT Taken together, these data suggest that cardio selective β-blockers may be beneficial in patients with COPD and pre-existing cardiac disease or hypertension, contrary to physicians' general reluctance to the use of these agents in COPD patients. Based on these data, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) is not opposed to using cardio selective β-blockers in hypertensive COPD patients.

IMPROVE ENDOTHELIAL FUNCTION ARBs and β-blockers are not only effective as antihypertensive agents but they have also been shown to improve endothelial function, which is common to both COPD and hypertension. Blockade of AT 1 receptor with ARBs has been shown to increase nitric oxide release, thereby reducing vasoconstriction. Similar to ARBs, some β-blockers (bopindolol, celiprolol, and nebivolol) have also been shown to possess vasodilator properties mediated by increasing nitric oxide availability. However, the only β-blocker that has shown to cause apparent increased endothelial nitric oxide release in humans has been nebivolol, albeit in a very small study. So in this patient with COPD and hypertension, an ARB or a β- blocker may provide additional benefits of improving endothelial dysfunction when used to lower blood pressure.

COPD AND PULMONARY HYPERTENSION

Pulmonary hypertension in the setting of COPD is a common occurrence, associated with poor survival. It manifests initially during sleep and with exercise, and in later stages it occurs at rest. In most cases PH is mild to moderate. COPD AND PULMONARY HYPERTENSION

PULMONARY HYPERTENSION AND COPD- NOT ALL ARE COR PULMONALE

NOT ALL PH ARE DUE TO COPD OUT OF PROPOTION PH PULMONARY ARTERIAL HYPERTENSION (PAH)- TYPE 1 PULMONARY EMBOLISM

There is a subpopulation of patients with COPD with moderate obstruction, severe hypoxemia, and a low DLCO who have significant PH and are recently termed "out of proportion PH." Workup of patients with COPD and PH should include a screening echocardiogram and evaluation for PE. If PE is excluded PAH type 1 may be considered and appropriate work should be done OUT OF PROPOTION PH

Patients with PH and COPD present with dyspnea and hypoxemia out of proportion to the degree of obstruction. Patients with COPD who develop signs of right heart failure, have right ventricular dilatation on echocardiogram, have dyspnea not fully explained by the degree of obstruction, and/or develop hypoxemia and a low DLCO out of proportion for their obstruction, should be suspected to be having out of proportion PH OUT OF PROPOTION PH

Pulmonary hypertension related to COPD is characterized by a relatively normal systolic right ventricular function (possibly diastolic dysfunction) and preserved cardiac output PAH patients in Group I are characterized by limitations in the right ventricular flow (cardiac output) and in advanced stages by a hypo contractile and dilated right ventricle. Although at risk for increased mortality, COPD patients with PH do not typically succumb to right ventricular failure.

COPD,SYSTEMIC HYPERTENSION AND PULMONARY HYPERTENSION TO R/O “OUT OF PROPOTION PH” CALCIUM CHANNEL BLOCKERS MAY HELP BOTH SILDANAFIL WILL BENEFIT BOTH (IF TYPE 1 PH) ARB MAY HELP BOTH IF B BLOCKERS HAVE TO BE USED ALWAYS USE NEBIVOLOL (NO DONOR)

CONCLUSIONS Hypertension is the commonest co morbid condition in COPD COPD itself can produce lot of systemic effects including systemic hypertension Ca channel antagonists are first choice ARB can be used as second line If indicated cardio selective b blockers should be used If associated with PH one should r/o “out of proportion PH’ All the drugs used for type 1 PH reduce systemic hypertension

END OF MODULE 3 CHAPTER 2 C