Hypertension with dyslipidemia can increase the risk of cardiovascular disease. The most common risk factors for cardiovascular disease are hypertension, dyslipidemia, diabetes, and smoking, etc. If these risk factors can be controlled, the incidence of coronary heart disease and mortality can be significantly reduced. Elderly patients with hypertension accompanied by dyslipidemia have both or more of these cardiovascular disease risk factors in addition to increased age. At present, a series of landmark statin lipid regulation trials have been completed at home and abroad, and the results of these studies have strongly demonstrated the importance of statin cholesterol-lowering in the primary and secondary prevention of coronary heart disease and related cardiovascular diseases.
However, in clinical practice, many patients with dyslipidemia and other high-risk factors, and even those who already have coronary heart disease, do not receive effective lipid-modifying therapy, especially in the elderly population. It is important to pay full attention to and actively intervene in the dyslipidemia of the elderly hypertensive population to improve the prevention and treatment of cardiovascular diseases.
Epidemiological background Currently, about 160 million people in China have varying degrees of dyslipidemia, of which about 70% are over 60 years old. The Framingham study showed that cholesterol levels are strongly associated with cardiovascular disease mortality and all-cause mortality in people over the age of 65. For every 10 mg/dl increase in total serum cholesterol, the relative risk of new coronary events increased by 1.12 and for every 10 mg/dl decrease in high-density lipoprotein cholesterol (HDL-C) levels, the relative risk of new coronary events increased by 1.7 to 1.95. Although with increasing age.
Total cholesterol levels in the elderly population showed a gradual decrease, but the effect of high-density lipoprotein cholesterol (HDL-C)emia and low-HDL-Cemia on cardiovascular prognosis was more significant. Moreover, risk factors such as increased age, dyslipidemia, hypertension and its abnormal glucose metabolism may have a superimposed effect on the cardiovascular system.
In addition, the prevalence of metabolic syndrome is higher, especially in the elderly in the advanced age group. Metabolic syndrome is diagnosed as a condition centered on insulin resistance with two of the blood pressure, lipid and glucose abnormalities. In the United States, the 2000 census data showed that MS has affected 24% of adults (20-70 years old), and the incidence of MS is predicted to increase. Epidemiological data in China show that the prevalence of metabolic syndrome in the general population is 13.25%, and the prevalence increases with age. The prevalence of metabolic syndrome in people aged 45 and 55 years or older is 2 times and 2.8 times higher than that in people aged 35 years or older, respectively, and the prevalence in people aged 55 years or older is as high as 20.26%.
The prevalence of metabolic syndrome in the Shanghai community is 17.14% among people aged 20-74 years old, with a significant increase in the prevalence of metabolic syndrome among men aged 45 years or older and women aged 50 years or older, with a peak at the age of 65-69. The prevalence of metabolic syndrome among people aged 60 years or older ranges from 18.83% to 24.36%, with 30.33% among the elderly group. Among metabolic syndrome, hypertension is the most common metabolic abnormality, with an incidence of 61.87%, and the incidence of 79.76% in elderly people older than 80 years old. The prevalence of metabolic abnormalities accounted for 46 67% of the total number of hypertensive patients, including 19 46% of hypertension with one other metabolic abnormality, accounting for 31. 49% of hypertension; the prevalence of hypertensive metabolic syndrome was 28 84%; the highest proportion of patients with metabolic syndrome combined with blood pressure abnormalities reached 89 57%, while only 10.43% of non-hypertensive MS patients.
Relationship between hypertension and dyslipidemia in the elderly The occurrence of hypertension and dyslipidemia in elderly patients is not causal but interactive. High levels of total cholesterol and/or triglycerides in the blood, as well as low levels of HDL cholesterol and/or high levels of LDL cholesterol in the blood, are closely related to the development of atherosclerotic disease and are necessary factors in the formation of atherosclerotic disease, which is the main cause of hypertension in the elderly.
In the early stage of hypertension, the whole body of fine and small arteries spasms, and the walls of the tubes become hypoxic and hyaline degeneration over time. When the pressure of small arteries continues to increase, the intima fibers and elastic fibers proliferate, leading to narrowing of the lumen and aggravating ischemia. With the development of fine and small arterial sclerosis and hypertension, secondary changes occur in various organs, of which the heart, brain and kidney are the most important. Hypertension can increase the afterload of the left ventricle, leading to myocardial hypertrophy and ventricular dilation, and heart failure can occur as the disease continues to progress. Persistent hypertension is more conducive to lipid deposition in the intima of large and medium arteries and atherosclerosis (such as combined coronary atherosclerosis) can lead to coronary heart disease and a series of myocardial ischemic diseases.
With aging, hypertension in the elderly shows the main characteristics of high systolic blood pressure, relatively low diastolic blood pressure, and increased pulse pressure difference. The main pathogenesis is a large number of cholesterol crystals, which aggravate the atherosclerotic plaque with the increase of lipid content, triglycerides inhibit fibrinolysis, which increases the tendency of blood coagulation and causes abnormal blood rheology, which in turn enhances the peripheral resistance of blood vessels as well as calcified deposits in the middle layer of large arteries, all of which decrease the elasticity of large arteries and the buffering capacity of pulse pressure.
The pressure generated by left ventricular systole is transmitted to the aortic system, resulting in an increase in systolic pressure, insufficient elastic retraction of the aorta during diastole, and consequent widening of pulse pressure. At the same time, the increase in blood pressure causes vascular stretching, stimulates smooth muscle cell proliferation, and causes damage to the intimal layer and endothelial cells, all of which have enhanced lipid deposition in the arterial wall and further promote the development of atherosclerosis.
Statins are the cornerstone of lipid-modifying therapy. They act on hepatocyte trihydroxytrimethyl coenzyme A (HMG CoA) reductase inhibitors to inhibit cholesterol synthesis and upregulate LDL-C receptors to accelerate the clearance of circulating LDL-C. Statins also have non-lipid-lowering effects such as improving endothelial function, stabilizing plaque to reduce inflammatory response and inhibiting thrombosis. etc.
Therefore, in addition to lipid regulation, elderly patients with hypertension have varying degrees of atherosclerosis and should pay attention to the improvement of arterial elasticity in addition to active antihypertensive therapy. Statins can inhibit smooth muscle cell proliferation and migration, increase plaque vascular smooth muscle and collagen-containing corona to determine lipid-containing corona, inhibit inflammatory response, reduce leukocyte adhesion to endothelial cells, improve abnormal plasma fibrinolytic activity, and also activate endothelial nitric oxide synthase, increase nitric oxide release, reduce oxygen radical production, prevent lipoprotein oxidation, and promote improvement of endothelial function in hypertensive patients. In turn, endothelium-dependent hemodilation is restored, which is conducive to further reduction of atherosclerotic plaques and hypertension and its complications. Short-term statin treatment has been reported to significantly improve the small artery elasticity index in patients with hyperlipidemia, resulting in a significant reduction in pulse pressure difference.
Evidence-based medical evidence Statins are recommended in national guidelines for the prevention and treatment of cardiovascular disease because they are considered safe and effective lipid-lowering agents. However, the benefits of any drug are accompanied by potential adverse effects and may increase with increasing drug doses. Since most of the available clinical trials have been done in carefully screened patients under 65 years of age at high risk for cardiovascular disease, the impact of intensive lipid lowering with this drug in clinical practice on the general population, whether the elderly population can benefit equally, and the safety of long-term treatment have become hot topics of research.
LDL-C is also a major target of lipid-lowering therapy in the intervention of dyslipidemia in elderly hypertensive patients. The HPS, PROSPER, and ASCOT trials showed that older adults benefited from LDL-C-lowering therapy and that this intensive LDL-C-lowering therapy significantly reduced the risk of cardiovascular disease in older adults. A 6-month follow-up found that the risk of Alzheimer’s disease decreased by approximately 79% in those treated with statins.
In the 4S study, 1,021 elderly patients aged 65 to 70 years with hypercholesterolemia who had coronary artery disease were followed for a mean of 5.4 years. Analysis of the elderly subgroup showed that simvastatin treatment reduced all-cause mortality by 34%, coronary mortality by 43%, and severe coronary events by 34% compared with placebo. Cerebrovascular events were reduced by 30%. The degree of benefit was similar to the group of patients under 60 years of age.
A total of 1283 elderly post-myocardial infarction patients aged 65 to 74 years with hyperlipidemia were randomized to pravastatin or placebo in the CARE study population and followed for a mean of 5 years. The results showed that treatment with pravastatin (40 mg/d) resulted in a 32% reduction in major adverse coronary events, a 45% reduction in coronary deaths, and a 40% reduction in strokes compared with the placebo group. The benefit was significantly greater than in the under-65 group.
Analysis of the LIPID study in a subgroup of 3514 of these older patients aged 65 to 75 years showed that after a mean of 8 years of treatment, pravastatin reduced all-cause mortality by 21%, coronary heart disease death by 24%, fatal or nonfatal myocardial infarction by 26%, and cardiovascular disease mortality by 26% in older patients. And the more risk factors for coronary heart disease, the greater the benefit to patients.
Of the 20,536 patients with coronary artery disease or non-coronary artery disease with total serum cholesterol levels ≥135 mg/dl enrolled in the HPS study, 5,806 were elderly patients aged 70 to 80 years. Patients were randomized to simvastatin (40 mg/d) or placebo and followed for 5 years, and a significant reduction in endpoint event rates was found in the older versus younger subgroups, regardless of the patient’s baseline cholestrol level at study enrollment.
The PROSPER study was a large clinical trial specifically designed for older adults, enrolling 5,804 patients aged 70 to 82 years with a history of coronary heart disease or its risk factors and a total serum cholestrol level ≥154 mg/dl. They were randomized to pravastatin 40 mg/d or placebo with a mean follow-up of 3.2 years. The results showed that pravastatin treatment reduced the incidence of the primary endpoint (coronary heart disease death, nonfatal myocardial infarction, or stroke) by 15%. And patient benefit was independent of their baseline LDL-C levels, but strongly correlated with baseline HDL-C levels.
Two large randomized clinical trials, ALLHAT and ASCOT, evaluated the effectiveness of statin lipid-modifying agents in the treatment of hypertension. The former showed a similar effect of lipid-modifying treatment as conventional treatment, and the latter showed a significant reduction in vascular events with lipid-modifying treatment. The CCSPS study completed in China showed that lipid-modifying therapy is beneficial for the secondary prevention of coronary heart disease in China.
The recent DUAAL study, the PROVET-IT study and the ARMYDA series have all confirmed the significant significance of statins in reducing inflammatory response, improving endothelial function, antioxidant effects and stabilizing plaque.
In conclusion, the results of evidence-based medical studies strongly suggest that for the primary and secondary prevention of ischemic cardiovascular disease in the elderly, lipid-regulating interventions with statins are effective in reducing the incidence of primary endpoint events and significantly improving patient prognosis. The degree of benefit is at least equal to that of middle-aged and younger patients. However, there are no results from large-scale randomized clinical trials on the use of statins in elderly people over 80 years of age, and there is a lack of evidence from clinical trials on the use of statins for primary prevention of coronary heart disease with lipid-lowering therapy in the elderly population, and there are no large-scale randomized, controlled clinical studies on the effects of statins on cognitive function, cardiac function, and immune function in the elderly.
Guidelines for the prevention and treatment of dyslipidemia The ATP III guidelines for the prevention and treatment of dyslipidemia are currently recognized as the definitive international guidelines. The guidelines recommend that serum LDL-C levels should be controlled to at least l00 mg/dl and may be considered to less than 70 mg/dl in all patients, regardless of age, who have a diagnosis of coronary heart disease and its equivalents (diabetes or other atherosclerotic vascular disease) or who have two or more risk factors and a 10-year risk of coronary heart disease of greater than 20%. If the patient also has hypertriglyceridemia or hypoHDL-Cemia, a fibrate or niacin may be added to statin therapy. For patients at intermediate risk (two or more risk factors, 10-year risk of coronary heart disease l0% to 20%), the target value of serum LDL-C should be <100 mg/dl.
For the above patients, serum LDL-C levels should be reduced by at least 30% to 40%. China’s newly issued “Guidelines for the Prevention and Treatment of Dyslipidemia in Adults in China” similarly emphasize dyslipidemia as an important cardiovascular risk factor in the elderly population. The guidelines set the same LDL-C target values for the elderly as for the general adult population (i.e., <100 mg/dl for high-risk patients and <80 mg/dl for very high-risk patients). However, the guideline states that the dose of lipid-lowering drugs should be individualized for elderly patients, that the starting dose should not be too high, and that the dose should be adjusted more carefully as needed with close monitoring of liver and kidney function and creatine kinase.
The 2007 Chinese Guidelines for the Prevention and Treatment of Dyslipidemia in Adults clearly states that statins are the most effective means of reducing LDL-C levels. Not only for secondary prevention of coronary heart disease, but also for patients with hypertension, diabetes and ischemic stroke without coronary heart disease. Effective drugs and their effective doses should be used adequately in clinical practice.
The application of statin lipid regulating therapy for hypertension in the elderly We add statins to our original antihypertensive drug therapy including calcium antagonists, angiotensin converting enzyme inhibitors (ACEI), β-blockers, diuretics, etc. Lipid regulation in the elderly is similar to that of young people. The first step is to change the lifestyle and reduce saturated fatty acids in the diet. However, intensive lipid lowering should not be advocated in the elderly, but rather individualized lipid regulating therapy, even in high-risk patients.
Recent data show that compared to younger patients, older patients over 65 years of age have decreased triglyceride (TC) and cholesterol (TG) levels and stable high-density lipoprotein (HDL-C) levels but reduced antioxidant activity. Taking the same dose of statins, elderly patients have to reduce their lipid levels by 3%-5% more than younger patients, and only half the dose of younger patients is needed to reduce LDL-C by 6% in elderly patients, plus aging, multi-organ decompensation, and coexistence of cardiovascular risk factors in elderly patients, especially in lean elderly female patients over 80 years old should be evaluated carefully, otherwise serious adverse effects are more likely to occur .
The use of statins generally does not produce significant adverse effects on liver and kidney function, and if it occurs, it is usually 1 to 3 months after the drug is used; statin-induced transaminase elevation is mostly transient, and persistent elevation does not exceed 1.2%, and about 0.7% leads to discontinuation of the drug; adverse effects on liver and kidney function are mostly related to the combined use of drugs (such as fibrates, antibiotics, anti-cancer drugs, etc.). If the liver enzymes are elevated due to statins, if they are higher than the upper limit of normal by 3 times, the drug should be stopped immediately and liver-protective drugs should be added; if they are lower than the upper limit of normal by 3 times, the dosage of statins should be reduced and liver-protective drugs and coenzyme Q10 should be added at the same time; liver function should be monitored closely at the same time.
If CK is elevated by statins, if it is 5 times lower than the upper limit of normal, the statin should be reduced; if it is 5 times higher than the upper limit of normal, the drug should be stopped; at the same time, CK should be monitored closely, and other drugs or factors causing CK elevation should be excluded, such as strenuous exercise and muscle injury, etc.
At present, clinical interventions are still inadequate, which may be attributed to the fact that elderly patients with hypertension take more types of drugs, which is one of the main reasons for the inadequate intervention of statins. In addition, the gradual decline in cholesterol levels in the elderly with age-related changes has obscured the problem of abnormal lipid profiles; at the same time, this has made the elderly more sensitive to statins. In the clinical setting, because fewer existing large-scale clinical trials include elderly patients over 80 years of age, more evidence-based medical evidence is needed for their lipid-lowering efficacy and safety. Therefore, a more cautious intervention strategy should be adopted for this population both to intervene in the presence of dyslipidemia and to discourage the use of high-dose statins.