Hypertension accompanying dyslipidemia. Dyslipidemia accompanying hypertension. Two chronic diseases are known to be representative risk factors for cardiovascular disease. Each of these two diseases, by itself, increases the risk of cardiovascular disease. More seriously, the two risk factors are often co-morbid. In addition, when the two diseases are co-morbid, the risk of cardiovascular disease is multiplied in a multiplicative manner. As the collective expression of cardiovascular disease risk factors and the resulting harms are widely known, the range of strategic options for drug treatment to control metabolic syndrome is also expanding. One of them is the Single Pill Combination (SPC) strategy to treat multiple comorbidities with one tablet. According to University of Ulsan University Professor Ki-Hoon Han (Department of Cardiology, Asan Medical Center), the SPC strategy started with a single-disease drug and has recently been making technological advances to a comorbid drug that targets multiple diseases at the same time. Four-agent complexes, which have been emerging one after another recently, are representative. Professor Ki-Hoon Han talked about the background of the emergence of four-agent complexes that target dyslipidemia and hypertension simultaneously and the prospects for clinical application.
Q. What is the prevalence of dyslipidemia and hypertension?
Both chronic diseases show differences according to age and gender. In the case of hypertension, men’s blood pressure levels start to soar from the age of 30 or older, and women show a high prevalence after menopause. Dyslipidemia is similar. In men, hyper-LDL cholesterol is close to 20% from the age of 30, and the prevalence approaches 30% or more in the age group of 60 or older.
In particular, hypertensive patients have a significantly higher risk of dyslipidemia compared to those without hypertension. According to the ‘Dyslipidemia Fact Sheet in Korea 2022’ of the Korean Society of Lipid and Arteriosclerosis, when LDL cholesterol of 160 mg/dL or higher is defined as hyper-LDL cholesterol, 59.9% of hypertensive patients are found to have dyslipidemia. When defined as 130 mg/dL or higher, the proportion of hypertensive patients with dyslipidemia was estimated to be 72.1%.
Q. Why do these two chronic diseases often co-morbid?
First, abdominal obesity affects the development of insulin resistance, and ultimately causes metabolic abnormalities due to hyperglycemia. Metabolic abnormalities due to insulin resistance do not stop here, and also act as a burden in the occurrence of hypertension and dyslipidemia. There is also a report that dyslipidemia increases the incidence of hypertension. In the study, the group with the highest total cholesterol (222 to 369 mg/dL) had a 28% higher incidence of hypertension than the group with the lowest total cholesterol (167 mg/dL or less). In addition, the incidence of hypertension in the group with the highest LDL cholesterol (138 to 301 mg/dL) was 27% higher than in the group with the lowest.
Q. What is the risk of cardiovascular disease in co-morbidities of dyslipidemia and hypertension?
The greater the comorbidity and severity of risk factors, the greater the risk of cardiovascular disease. The seriousness of the problem is that the increase in risk is multiplied multiplicatively, not additively. Therefore, in this case, it is most important to block the occurrence of cardiovascular disease in advance through active treatment from the time of diagnosis of the two risk factors or before.
When dyslipidemia is accompanied by other cardiovascular disease risk factors, multiple drugs are taken at once to treat each risk factor, and in this case, medication compliance is poor. The single pill combination (SPC) strategy emerged to solve this problem. It is intended to reduce the burden of taking multiple medications and treat multiple accompanying chronic diseases with one tablet. It is for the same reason that a number of complex drugs applied to patients with dyslipidemia and hypertension are being developed.
Q. What is the prevention strategy for cardiovascular disease in patients with dyslipidemia?
It is important to accurately measure the risk of cardiovascular disease and provide more aggressive treatment one step ahead. According to the guideline, even if there is no cardiovascular disease, if there is a comorbidity such as hypertension or dyslipidemia, or if renal dysfunction or diabetes are added, it is considered as a level equivalent to that of a person with a history of cardiovascular disease, and active treatment of each risk factor is recommended. . In particular, in recent years, carotid artery ultrasound is often performed in private practice, and if multiple risk factors and asymptomatic atherosclerosis are identified, the guideline recommends thorough treatment of blood pressure and dyslipidemia at the same level as those with a history of cardiovascular disease.
If dyslipidemia is accompanied by asymptomatic atherosclerosis in addition to hypertension, diabetes, kidney disease, etc., even if there is no cardiovascular disease, it is considered a high or ultra-high risk group and LDL cholesterol must be strongly controlled. In recent guidelines, even lowering LDL cholesterol to less than 55 mg/dL has been recommended for patients in the ultra-high risk group for cardiovascular disease.
Q. What is the current state of the dyslipidemia combination drug strategy?
As the IMPROVE-IT study demonstrated the benefits of secondary prevention of cardiovascular disease of the combination of statin, a cholesterol synthesis inhibitor, and ezetimibe, a cholesterol absorption inhibitor, the development and application of combination therapy or combination therapy began to gain momentum. Ezetimibe, in particular, has been suggested for primary prevention of cardiovascular disease through the EWTOPIA75 study, which was conducted in Japan for people aged 75 years or older, so it is possible to review the omnidirectional application of the statin/ezetimibe combination strategy.
Q. The 4-agent complex ‘Nouveau Rosette’ has been released?
The SPC (Single Pill Combination) strategy started from a single disease combination drug and is currently expanding its scope to the stage of multiple or cross-over of a single disease combination drug for a comorbid disease. A typical example is a 4-drug combination that combines a 2-drug combination for hypertension and a 2-drug for dyslipidemia into one tablet. The most recent four-drug combination drug is ‘Nouvorojet,’ which is a combination of four ingredients in one tablet, including antihypertensive drugs telmisartan and S-amlodipine, and lipid therapeutics rosuvastatin and ezetimibe.
The feature of this four-drug complex is that it contains drugs that are rated as first-class in each class and are frequently prescribed, such as angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and statins and cholesterol absorption inhibitors, all in one tablet. Telmisartan has a long half-life and high durability of effect, S-amlodipine has improved tolerability due to reduced risk of side effects, and rosuvastatin and ezetimibe have clinical evidence in various fields, such as cardiovascular disease prevention benefits. Given the opportunity to select various doses, it is expected that patients with co-morbidity with multiple risk factors such as metabolic syndrome will be able to provide another option for customized treatment with high medication compliance and drug price feasibility.