Yan Wenming, Department of Radiotherapy, Affiliated Hospital of Inner Mongolia Medical University
Sun Dongfeng Yan Wenming (Reviewer)
Chinese Journal of Practical Medicine, Vol. 7, No. 12, 2007
With the development of large-scale anti-hypertensive clinical trials and advances in cardiovascular molecular biology research in recent years, the traditional understanding of hypertension has been updated, and evidence-based medicine has become the consensus. Hypertension is not only an abnormal hemodynamic disease, but also accompanied by disorders of lipid and glucose metabolism and adverse remodeling of target organs such as the heart, brain and kidney. Therefore, the treatment should improve the above metabolic disorders and prevent and reverse the adverse remodeling of target organs while effectively controlling the blood pressure level, which is the key to reduce the occurrence of cardiovascular complications and morbidity and mortality. In Dalby, GPPT, GBPCS and other studies with a follow-up of 3-10 years, the incidence of cardiovascular complications and death in patients with hypertension in the treatment group was still much higher than in the normal blood pressure population in the same area, the most likely explanation is that these patients The most likely explanation is that the blood pressure drop obtained by these patients is not the most appropriate, so it is very important to achieve the ideal blood pressure level. What is the ideal target blood pressure level? The results of the largest, 3-year HOT clinical trial to date, which has been successfully completed, showed that the lowest incidence of cardiovascular events occurred when blood pressure dropped to 138/83 mmHg (1 mmHg = 0.133 kPa). In addition, it is also very safe for blood pressure to fall below this level.
II. Pharmacological treatment of hypertensive patients
(A) Evaluation of anti-hypertensive drugs 1. Diuretics: Many clinical trials in Europe and the United States, such as EWPHE, SHEP, STOP and MRC, found that by applying small doses of thiazide diuretics, the occurrence of stroke and coronary events and the reversal of left ventricular hypertrophy could be more significantly reduced than high doses, and there was no adverse effect on sugar, fat and electrolyte metabolism. Indapamide, as a non-thiazide diuretic, has calcium antagonistic effects in addition to diuretic effects, and is a mild and effective antihypertensive agent with a protective effect on the heart. It has no adverse effects on glucose and lipid metabolism, and is a long-acting ideal antihypertensive drug. 2. β-blockers: Large-scale clinical trials have demonstrated that it can reduce coronary events and has a secondary prevention effect on myocardial infarction (MI), but it has not been proven whether it is better than diuretics in preventing the occurrence of MI in hypertensive patients. The CIBSI I trial confirmed that bisoprolol is well tolerated and improves cardiac function if administered carefully and gradually, but does not improve overall survival.3. Calcium antagonists (CCB): There are three main classes, of which dihydropyridines, the most vasoselective, are the most used. Used for the treatment of hypertension and coronary artery disease, good results have been achieved. In the Systolic Hypertension in the Elderly Clinical Trial in China (Syst-China) and the European Systolic Hypertension in the Elderly Clinical Trial (Syst-Eur), two studies showed similar results, with a protective effect on the cardiovascular system and a 40% reduction in the incidence of stroke compared to the control group after 2 to 3 years of taking nidulodipine, and no significant increase in adverse effects such as cardiovascular events, cancer and bleeding. The 1999 guidelines for the treatment of hypertension published by the International Society of Hypertension (WHO-ISH) state that calcium antagonists are effective in lowering blood pressure in all subgroups of hypertensive patients, are well tolerated, and have a beneficial effect in preventing stroke in elderly patients with hypertension. It is best to use long-acting calcium antagonists and avoid short-acting agents.4. Angiotensin-converting enzyme inhibitors (ACEI): ACEI has a strong antihypertensive effect and can reverse the poor remodeling of the blood vessel wall and heart, restoring its structure and function. It can also improve insulin resistance and has no adverse effect on the metabolism of sugar and fat. ACEI can prevent or reverse glomerular basement membrane glycation, effectively delaying the progression of nephropathy in insulin-dependent diabetic patients, especially those with proteinuria, and improving the prognosis of patients. CAPPP clinical trials suggest that ACEI can effectively reduce the rate of disability and death in patients with heart failure.5. Angiotensin II receptor blockers: Angiotensin II receptor blockers introduced in recent years are closer to ACEI in terms of hemodynamic properties, but whether the long-term benefits to the heart and kidney are similar to those of ACEI is yet to be verified in more clinical trials. The advantage of these drugs over ACEI is the absence of coughing side effects. 6. alpha-blockers: precise antihypertensive, may be beneficial for people with hyperlipidemia and abnormal glucose tolerance. It can reverse left ventricular hypertrophy, improve insulin resistance, and significantly improve urinary difficulties in patients with prostatic hypertrophy. So far, clinical trials have not demonstrated that long-term application can reduce the incidence of cardiovascular complications and morbidity and mortality.
(B) initial drug therapy and drug combination 1. initial drug therapy: in principle, different drugs should be selected according to the patient’s condition, without emphasizing the role of first-line drugs and insisting on individualization as the treatment guideline. the WHO-ISH believes that any class can be used as initial drugs in the following order: diuretics, beta-blockers, ACEI, CCB, alpha-blockers. The US Joint National Committee (JNCVI) report states that initial treatment of patients without indications for other drugs should be diuretics or beta-blockers, because a large number of randomized controlled clinical trials have demonstrated that these two drugs can significantly reduce morbidity and mortality in patients. When intolerant or ineffective, ACEI, CCB, and α-blockers are then used.2. Long-acting drugs: The new WHO-ISH guidelines for the treatment of hypertension advocate a 1-day long-acting formulation in drug dosage form, which has the following advantages: it is easy for patients to accept; it is more sustained and smooth in lowering blood pressure than short-acting formulations and has the potential to protect target organs; taking long-acting formulations can avoid patients taking short-acting drugs due to missed doses or at night 3. Small doses of combination drugs: drug therapy should be started in small doses to reduce adverse effects. If the patient responds well to a single drug but the blood pressure does not reach the target, the dose of the drug should be increased if the patient can tolerate it well. Possible dose-related side effects can be minimized by combining drugs to minimize blood pressure reduction. If a drug has a poor response or is poorly tolerated, it may be possible to switch to another type of drug rather than increasing the dose of the first drug or adding a second drug.
Third, special types of hypertension or complications or comorbidities of drug selection principles 1. elderly hypertension: systolic blood pressure in the elderly is a risk factor for coronary heart disease, heart failure, stroke, end-stage renal disease total morbidity and mortality, systolic blood pressure is more dangerous than diastolic blood pressure elevation. The clinical trials of SHEP, Syst-Eur, and Syst-China have demonstrated that the antihypertensive treatment group can reduce the incidence of cardiovascular complications and morbidity and mortality in these patients. The dose of medication should be 1/2 that of young people due to degeneration of the parabolic apparatus, lower plasma renin activity (PRA), and varying degrees of hepatic and renal function. long-acting calcium antagonists are preferred and are effective for simple systolic hypertension, followed by ACEI.
The standard for lowering blood pressure in the elderly should be <140/90mmHg as in young people, systolic blood pressure can be <160mmHg, if not achieved, the closer to normal the better. Avoid drugs that can cause postural hypotension (e.g., alpha-blockers, high-dose dihydrocortisone) and drugs that affect cognitive ability (e.g., colistin, methyldopa). it is still debated whether to treat hypertension in the elderly over 85 years of age. However, those with very high blood pressure or those with target organ damage should be treated medically.2. Hypertensive left ventricular hypertrophy (LVH): The most important complication of hypertension, a combination of hemodynamic factors (volume and pressure load) and neurohumoral factors (e.g., epinephrine, angiotensin II, endothelin, pressors, etc.) leads to LVH. the latter is more important than the former. Various antihypertensive drugs, except hydrazinpyridazine and long-pressin, can reduce LVH. salt restriction and weight reduction are effective in reducing LVH, and ACEI + diuretics are better than all other drugs. improvement in ECG indicators of LVH predicts a reduced risk of cardiovascular disorders, but it is not clear whether it is the effect of LVH reduction or blood pressure decrease. 3. angina pectoris or MI in coronary artery disease: lowering blood pressure for patients with coronary artery disease There are definitely benefits, but it is important to avoid lowering blood pressure too quickly and causing reflex tachycardia and sympathetic tension. The first choice for such patients is beta-blockers with long-acting calcium antagonists. beta-blockers without intrinsic sympathomimetic effects should be used after MI to reduce recurrent MI and sudden death, and ACEIs are also available after MI. the CCS-1 clinical trial confirmed that early treatment of acute MI (AMI) with captopril is safe and beneficial, especially for those with anterior wall infarction and normal or rapid heart rate. ACEIs can prevent heart failure and reduce morbidity and mortality. ACEI can prevent heart failure and reduce mortality. (Verapamil or diltiazem can be used in the case of Q-free MI or good cardiac function after MI). In some patients with hypertension combined with LVH, the onset of angina is not necessarily due to coronary artery stenosis, but to an imbalance in myocardial oxygen supply and demand.4. Cerebrovascular disease: Hypertension is the most important risk factor for hemorrhage or ischemic stroke. It is generally accepted that in early acute ischemic stroke, unless the blood pressure is very high (e.g., >180/105 mmHg), antihypertensive drugs should be suspended until the condition is stable. Otherwise, excessive blood pressure lowering can significantly reduce cerebral blood flow. Blood pressure should be monitored for 24 hours with thrombolytic therapy in cerebral infarction, and blood pressure should be controlled with intravenous antihypertensive drugs only if it is >180 mmHg/105 mmHg. Blood pressure in hemorrhagic stroke is significantly elevated and should be urgently lowered. 5. Renal lesions: All CCBs and ACEIs are known to have renal protective effects. The results of the well-known AIPRI trial showed that long-term application of dual-channel excreted benazepril reduced urinary protein and delayed the progression of renal failure in patients with renal insufficiency. The blood pressure should be reduced to 130/85 mm Hg, and the target blood pressure should be 125/75 mm Hg if proteinuria is >1 g/d. ACEIs, especially dual-channel excretory ones, should be used first in patients with renal insufficiency, but should be started at low doses and renal function should be closely monitored. In addition, CCB, loop diuretics and alpha-blockers can be used. 6. Hypertension combined with diabetes mellitus: Lifestyle improvement and antihypertensive drug therapy have the same effect, and blood pressure must be controlled below 130/85 mm Hg. ACEI, alpha-blockers, calcium antagonists and low-dose dihydrocortisone are most suitable for this kind of patients. patients. Although β-blockers affect peripheral blood flow, prolong the duration of hypoglycemia and mask the symptoms of hypoglycemic response, treatment with diabetic patients with dihydrocoumarotide plus β-blockers is certainly effective in reducing coronary heart disease mortality and total cardiovascular events. Non-insulin-dependent diabetes mellitus is combined with nephropathy in 1/3 of cases and is one of the most common causes of nephropathy. Antihypertensive therapy may delay or stop the progression of renal impairment and prolong life expectancy. The choice of antihypertensive drugs is very important for the presence or absence of nephropathy, and some drugs themselves can accelerate the occurrence of metabolic complications of diabetes. ACEI, alpha-blockers and diuretics after antihypertensive therapy can increase the survival of patients from 30% to 80% for 10 years after the appearance of proteinuria. ACEI is the drug of choice, which not only slows down the progression of nephropathy, but also in diabetic patients with normal blood pressure, which is the most recent years ACEI clinical application of the biggest breakthrough, if ACEI is not suitable for application then consider angiotensin II receptor antagonists. Generally, the blood pressure should be reduced to the lowest level to maintain the perfusion pressure of the major organs, which can enhance the efficacy of anti-renal disease.7. Hyperlipidemia: Weight reduction is preferred, limiting total calories, fatty acids, cholesterol (TC), salt and alcohol, and strengthening physical exercise. High-dose dihydrocoumaric acid and loop diuretics cause a transient increase in TC, triglycerides (TG), and low-density lipoprotein (LDL), but diet modification can reduce or eliminate this side effect. These side effects are not seen with low doses of dihydrocortisone, which definitely reduces the rate of sudden death, total mortality and MI recurrence in these patients. α-blockers reduce TC and increase HDL. ACEI, angiotensin II receptor antagonists, calcium antagonists and central sympathetic stimulants have a neutral effect on lipids. And statins have primary and secondary preventive effects on coronary heart disease and stroke.8. Pregnancy: Hypertension in pregnancy is generally defined as elevated absolute blood pressure (140/90 mmHg or higher) or elevated blood pressure levels before or during the first trimester of pregnancy [systolic blood pressure elevation ≥ 25 mmHg and/or diastolic blood pressure ≥ 15 mmHg]. Blood pressure >170/110 mmHg should be treated, but to date there is no definitive conclusion about the level to which blood pressure should be lowered. The drugs that are used to urgently reduce hypertension in pregnancy are nifedipine, hydrazidiazide, and labetalol. Medications used for long-term treatment of hypertension in pregnancy include beta-blockers (atenolol is used throughout pregnancy and can be associated with fetal growth retardation), methyldopa, prazosin, hydrazidiazide, and nifedipine. Drugs generally avoided during pregnancy include ACEI, angiotensin II receptor antagonists, and diuretics.9. Perioperative hypertension: may be associated with increased adrenal function. Blood pressure >180/110 mmHg increases the incidence of perioperative MI and stroke. Surgery should be postponed, and β-blockers are best used to lower blood pressure, followed by diuretics, sympathetic nerve inhibitors, ACEI, and patch colistin. Potassium should be supplemented before surgery to prevent postoperative potassium deficiency. Patients who are well controlled with antihypertensive drugs should resume medication immediately after surgery, and if oral administration is not possible, sedative antihypertensive drugs can be used. Individual reports suggest that calcium antagonists increase intraoperative bleeding.10. Hypertensive crisis: Hypertensive crisis includes both emergency and subacute situations. Hypertensive emergencies are those that require immediate lowering of blood pressure (not necessarily to the normal range) to prevent or reduce target organ damage, such as hypertensive encephalopathy, intracranial hemorrhage, unstable angina, AMI, acute heart failure with pulmonary edema, coarctation aneurysm, or eclampsia. Hypertensive sub-emergencies are those conditions in which a reduction in blood pressure is expected within a few hours, including, for example, levels of stage III hypertension, hypertension with optic nerve papilledema, progressive target organ complications and severe perioperative hypertension. Simple elevation of blood pressure in the absence of symptoms or without new, progressive target organ damage is very rare. Many hypertensive emergencies are treated by non-gastrointestinal administration, or faster-acting oral agents can be given. Options include loop diuretics, β-blockers, ACEIs, α2-blockers, or calcium antagonists.