Decision-making and the Art of Combination Therapy for Hypertension Comorbidities: From Dyslipidemia and Cardiovascular Risks to Principles of Achieving Target Blood Pressure

How should patients with hypertension and dyslipidemia (hyperlipidemia) choose antihypertensive drugs?

Dyslipidemia (hyperlipidemia) is a common complication of hypertension, and many hypertensive patients also have dyslipidemia. Both hypertension and dyslipidemia are major risk factors for coronary heart disease. When hypertensive patients also have dyslipidemia, the risk of coronary heart disease increases significantly. The principle for choosing antihypertensive drugs when hypertension is complicated by dyslipidemia is to select drugs that do not negatively affect the patient's lipid levels while lowering blood pressure. Currently, the following are some ideal drugs:

① Alpha-blockers: These are the first-line antihypertensive drugs for patients with hypertension and dyslipidemia. They have both vasodilatory and lipid-regulating effects. They are also more suitable for patients with benign prostatic hyperplasia (BPH). Commonly used drugs include prazosin (Veline), with an initial dose of 0.5 mg taken at bedtime, followed by 0.5 mg 2-3 times daily; terazosin (Gortzin), with an initial dose of 1 mg taken at bedtime, followed by 2 mg once daily, is also used for benign prostatic hyperplasia. Doxazosin (Bixinya) can also be used, with 1 mg once daily. During medication, it is important to prevent orthostatic hypotension, and avoid getting up at night to fall asleep.

② Angiotensin-converting enzyme inhibitors (ACEIs): Short-acting captopril (Capoton) can be used, 12.5 mg 2-3 times daily; or intermediate-acting enalapril (Enalapril), 5 mg 1-2 times daily; or long-acting benazepril (Lotensin), 10 mg once daily, or fosinopril (Monopril), 10 mg once daily. The latter is excreted through both the kidneys and bile ducts, offering protection to the liver, kidneys, and viscera, and is suitable for patients with impaired liver and kidney function.

③ Angiotensin II receptor antagonists (ARBs): Suitable for patients who cannot tolerate ACEIs. Commonly used ones include losartan (Cozaar), 50 mg once daily, or valsartan (Diovan), 50 mg once daily.

④ Calcium channel blockers (CCBs): Short-acting dihydropyridine preparations such as nifedipine (Adalat) can be used, suitable for hypertensive patients with bradycardia, 5 mg three times daily; or long-acting controlled-release tablets (Adalat), 30 mg once daily; or long-acting fenardipine extended-release tablets (Plendil), 5–10 mg once daily; or amlodipine (Lovacecoxib), 5 mg once daily. For hypertensive patients with a rapid heartbeat, verapamil (Isoptin) can be used, 40mg each time, three times a day. Diltiazem (Dietaril) can also be used.

Which antihypertensive drugs should not be used when hypertension is complicated by dyslipidemia (hyperlipidemia)? The following antihypertensive drugs should not be selected:

① Diuretics: Long-term use of diuretics such as hydrochlorothiazide and chlorthalidone can increase serum total cholesterol and triglyceride levels. Furosemide (Lasix) can lower serum high-density lipoprotein cholesterol levels. Why is this? It is generally believed that it may be related to abnormal glucose metabolism. When diuretics are used to treat hypertensive patients, blood insulin levels increase, and blood glucose also increases, while glucose tolerance decreases, indicating that the body has developed insulin resistance. This resistance can reduce glucose utilization on the one hand, and weaken the effect of insulin on fat breakdown on the other hand. These two effects will enhance fat breakdown, increase free fatty acids in the blood, and accelerate the synthesis of very low-density lipoprotein cholesterol in the liver, thereby increasing the levels of very low-density lipoprotein cholesterol and triglycerides in the blood. However, its effect on lowering high-density lipoprotein cholesterol (HDL-C) is relatively mild.

② Beta-blockers: Non-selective beta-blockers [such as propranolol (Inderal)] and selective beta-blockers [such as metoprolol (Betaloc), atenolol (Aminophylline), etc.] generally increase triglyceride levels and decrease HDL-C levels after 2 weeks of use; after 1 year of use, they not only increase triglycerides and decrease HDL-C levels, but also increase serum total cholesterol and LDL-C levels. ③ Compound antihypertensive tablets: Compound antihypertensive tablets can increase triglycerides and cholesterol, and decrease HDL-C.

Which type of antihypertensive drug should be chosen when hypertension is complicated with coronary heart disease?

Hypertension is an important risk factor for coronary heart disease. The incidence of coronary heart disease in hypertensive patients is 2 to 4 times higher than that in people with normal blood pressure. Coronary heart disease can manifest as angina pectoris, myocardial infarction, heart failure, arrhythmia, and even asymptomatic sudden death (sudden death). Therefore, in drug selection, it is necessary to consider drugs that can both lower blood pressure and improve coronary artery blood supply and reduce myocardial oxygen consumption. The following three categories of antihypertensive drugs are available:

① Beta-blockers: These reduce myocardial contractility, slow heart rate, decrease cardiac output, reduce myocardial oxygen consumption, and decrease central sympathetic nerve activity and peripheral vascular resistance, thereby effectively controlling hypertension and angina. They can also reduce the extent of acute myocardial infarction and lower the incidence of sudden death and re-infarction. Therefore, beta-blockers should be the first-line treatment for patients with hypertension complicated by myocardial infarction or angina. Some hypertensive patients, especially those with left ventricular hypertrophy, may experience angina but without clear evidence of coronary artery sclerosis. This is related to an imbalance between myocardial oxygen demand and supply, reflecting impaired coronary microcirculation. For these patients, treatment should focus on directly controlling blood pressure, reversing left ventricular hypertrophy, and preventing tachycardia. Therefore, beta-blockers should be used when there are no obvious contraindications. ② Angiotensin-converting enzyme inhibitors (ACEIs): The main prognostic factor for coronary heart disease and myocardial infarction is the deterioration of cardiac function. ACEIs can effectively protect and improve cardiac function after infarction, improve quality of life, and increase survival rate. Therefore, these drugs can be used for such patients, especially when there is left ventricular systolic dysfunction after myocardial infarction.

③ Calcium channel blockers (CCBs): These drugs can dilate peripheral blood vessels and coronary arteries, lowering blood pressure. Clinical practice has confirmed that these drugs have good left ventricular selectivity, increase perfusion of the brain, heart, and kidneys, and protect these organs. These drugs also have varying degrees of coronary artery dilation, antiarrhythmic effects, antiplatelet aggregation effects, vascular endothelial protection, prevention of atherosclerotic plaque formation, reduction of cardiac load, reduction of myocardial oxygen consumption, and relief of coronary artery spasm. Therefore, they are more suitable for elderly hypertensive patients with coronary heart disease, coronary artery spasm, variant angina, and chronic obstructive pulmonary disease. At the 2005 Asian Cardiology Conference, experts unanimously agreed that nifedipine controlled-release formulations, i.e., dihydropyridine calcium channel blockers, combined with ACEIs or ARBs, is the best combination for treating hypertension complicated with coronary heart disease.