Arterial Hypertension and Metabolic Disorders: Rethinking Treatment Strategies in Cardiometabolic Patients
Arterial hypertension in combination with metabolic disorders differs significantly from hypertension in their absence. Achieving successful treatment outcomes in patients with this comorbidity may require not only intensification of therapy, but also a complete change in the approach to pharmacotherapy and its goals.
The issue of how to intensify baseline antihypertensive therapy in order to maintain blood pressure control, improve prognosis, and enhance quality of life is becoming increasingly relevant in modern clinical practice.
Metabolic Risk as a New Focus in Patients with Hypertension
Hypertension has always required an individualized therapeutic approach, and treatment has traditionally been selected separately for each patient. In some cases, the target is achieved quickly, while in others it takes more time. Standard baseline therapy usually consists of fixed-dose combinations of ACE inhibitors or angiotensin receptor blockers, calcium channel blockers, and diuretics. The main goal is to normalize blood pressure to approximately 130/80 mmHg in order to prevent complications, particularly major cardiovascular events.
However, cardiovascular risk is no longer the only focus in clinical decision-making. Today, the concept of cardiometabolic risk has become central in the management of patients with hypertension and dyslipidemia. When a patient presents with both arterial hypertension and metabolic disorders, these conditions act as a double burden on the vascular system. As a result, pharmacotherapy should be aimed not only at reducing blood pressure, but also at modifying the metabolic component of risk.
Up to 80% of patients with arterial hypertension have one or more components of metabolic syndrome. Patients with insulin resistance, obesity, hypertriglyceridemia, metabolic dysfunction-associated steatotic liver disease (MASLD), or elevated levels of lipoprotein(a) and triglyceride-rich lipoproteins require more than the conventional first-line medications used for hypertension and dyslipidemia.
The Global Burden of Cardiometabolic Disease
According to recent evidence, cardiometabolic diseases represent one of the largest health challenges of our time. We are living in an era of a global burden of cardiometabolic disorders that significantly shorten life expectancy.
To better understand this burden, the concept of DALYs (Disability-Adjusted Life Years) was introduced. Between 1990 and 2023, the number of years of healthy life lost due to disease increased by 43% in men and by 28.6% in women. The overall burden of cardiovascular disease also continues to rise. Importantly, approximately 80% of these DALYs are associated with modifiable risk factors.
The most under-addressed areas remain dyslipidemia control, blood pressure control, obesity management, and prevention of type 2 diabetes. These are especially challenging in low-resource settings, yet they also represent a major opportunity for preventive medicine.
Key Metabolic Factors That Increase Cardiovascular Risk
The most important metabolic factors contributing to cardiovascular disease burden include:
- Elevated fasting glucose (5.6–6.9 mmol/L)
- Elevated low-density lipoprotein cholesterol (>3.37–4.12 mmol/L)
- Elevated blood pressure (≥140/90 mmHg)
- Obesity (BMI >30 kg/m²)
- Impaired kidney function (increased creatinine and urea, decreased glomerular filtration rate)
Clinical Practice Example
A typical clinical case may look as follows:
- Female, 55 years old
- Stage 2 arterial hypertension (155/95 mmHg)
- Type 2 diabetes mellitus (HbA1c 7.8%)
- Triglycerides: 3.3 mmol/L
- HDL cholesterol: 1.0 mmol/L
- LDL cholesterol: 2.6 mmol/L
- Waist circumference: 92 cm
- BMI: 30.1 kg/m²
- Waist-to-height ratio: 0.55
- GFR: 76 mL/min
- FIB-4: 1.8
In this patient profile, the presence of liver involvement is particularly notable, since a FIB-4 score of 1.8 suggests an unfavorable level consistent with the development of fibrosis. This supports the diagnosis of MASLD, which can be regarded as a hepatic phenotype of cardiometabolic risk. MASLD is associated with hypertriglyceridemia, a marker and mediator of adiposopathic dyslipidemia, which in turn is characterized by elevated triglyceride-rich lipoproteins. These particles contribute to endothelial dysfunction, which promotes elevated blood pressure and worsens insulin resistance.
This creates a vicious cycle that cannot be broken unless clinicians recognize that obesity and insulin resistance are commonly associated with hypersympathicotonia, one of the mechanisms of increased blood pressure.
According to the 2025 AHA guidance for cardiologists, internists, and family physicians, the liver plays a central role in endothelial dysfunction, chronic inflammation, gut microbiome disturbances, lipid metabolism abnormalities, insulin resistance, abdominal fat accumulation, and oxidative stress. Together, these processes contribute to the progression of cardiovascular disease.
Therefore, in addition to SCORE2, clinicians should also use the FIB-4 score in routine cardiometabolic assessment. This also implies the need for liver ultrasound and selection of therapies capable of improving liver function.
Adiposopathic Dyslipidemia
The term adiposopathic dyslipidemia has been used in expert consensus documents from American professional associations addressing dyslipidemia. It refers to a lipid metabolism disorder commonly associated with obesity and includes four main components: elevated triglycerides and postprandial triglyceride-rich remnant lipoproteins, decreased HDL cholesterol and ApoA1, increased concentrations of ApoB-containing particles including LDL, and an increased number of small dense LDL particles.
Ten Key Clinical Statements for the Management of Patients with Adiposopathic Dyslipidemia
- Obesity is a serious, chronic, relapsing, multifactorial disease that progresses and is treatable.
- Even modest weight loss improves most cardiometabolic risk markers.
- Lifestyle modification, including healthy nutrition and physical activity, is the foundation of therapy for all patients.
- Most lipoproteins contributing to atherosclerosis are ApoB-containing particles.
- Non-HDL cholesterol is one of the most important predictors of atherogenic particle burden because it includes LDL-C, IDL-C, VLDL-C, and Lp(a).
- Patients with overweight and obesity typically have atherogenic dyslipidemia characterized by elevated triglycerides, low HDL-C, and elevated non-HDL cholesterol.
- Statins reduce atherogenic particles but may not always be sufficient to offset the increased atherosclerotic cardiovascular risk in obesity.
- More aggressive reduction of non-HDL cholesterol and ApoB may be necessary, since standard LDL-C lowering may inadequately reduce atherogenic particle burden.
- Patients with overweight or obesity should receive a combination of healthy nutrition and physical activity, with a target of at least 5% weight loss, and ideally 10–15%, to reduce triglycerides and improve overall metabolic status.
- Weight loss of 10–15% usually results in only moderate LDL-C reduction, so lipid-lowering medications may still be necessary.
Why Triglycerides Deserve Special Attention
The answer lies in triglyceride metabolism, which depends on several lipases and two major organs: the intestine and the liver.
Hypertriglyceridemia, a hallmark of adiposopathic dyslipidemia, may occur in a variety of pathological settings and is often associated with poor dietary habits, including excessive caloric intake, diets rich in refined fats and simple sugars, alcohol overconsumption, and physical inactivity.
At present, atherogenic or adiposopathic dyslipidemia in combination with obesity is clearly defined by:
- Fasting triglycerides ≥1.7 mmol/L
- Non-HDL cholesterol ≥3.4 mmol/L
- ApoB ≥1.8 mmol/L
These three parameters are directly linked to the formation of atherosclerotic plaques and are also essential for assessing residual cardiovascular risk. Without normalizing them, it is not possible to adequately protect the patient from recurrent or new cardiovascular events.
Pharmacologic Reduction of Triglycerides
Fibrates are the main lipid-lowering agents used to reduce triglyceride levels. Their efficacy has been best studied in patients with metabolic disorders, both in terms of triglyceride reduction and clinical outcomes.
According to numerous studies, these medications may also reduce the risk of microalbuminuria and kidney damage. By the end of 2025, several important publications also reported on the use of fenofibrate in patients with MASLD. A meta-analysis of 15 studies, including randomized clinical trials, showed that fenofibrate significantly reduced ALT, AST, and GGT, improved liver biochemistry, and had a positive effect on insulin resistance.
Another 2025 study focused on heart failure, especially in patients with diabetes. Researchers compared statin plus fenofibrate combination therapy with statin monotherapy and found that, in patients with diabetes, the combination was associated with a lower risk of heart failure, which has important clinical implications.
However, fibrates are not all the same. Fenofibrate has demonstrated benefit in randomized clinical trials, including in populations with atherogenic or adiposopathic dyslipidemia. It has shown the ability to improve quality of life and prognosis and to reduce the risk of atherosclerosis progression.
By contrast, pemafibrate, although capable of improving lipid parameters, has not demonstrated the same reduction in cardiovascular risk. This distinction should be kept in mind in routine clinical practice.
Returning to the Clinical Case: What Should Be Added?
In the example above, baseline therapy did not help the patient control blood pressure. This is often the case in patients with obesity and other metabolic disorders.
In such circumstances, treatment should include medication aimed at controlling the autonomic nervous system. As noted earlier, hypersympathicotonia is one of the mechanisms responsible for increased blood pressure. In patients with metabolic disorders, blood pressure depends not only on RAAS activation but also on activation of the sympathetic branch of the autonomic nervous system. Therefore, success requires control of both pathways.
An imidazoline receptor agonist such as moxonidine may therefore be used to inhibit sympathetic nervous system activity and norepinephrine release, leading to reduced vasoconstriction and lower blood pressure.
This molecule also has a substantial evidence base specifically in patients with systemic metabolic disorders, including obesity, overweight, type 2 diabetes, insulin resistance, chronic kidney disease, and MASLD.
Another clinically relevant feature of moxonidine is its favorable impact on body mass index and waist circumference, as demonstrated in the MERCY study. This may also positively influence treatment adherence.
In this context, moxonidine may be considered not merely as an add-on option, but at the same level as baseline therapy — effectively as part of first-line treatment in appropriately selected cardiometabolic patients. Waiting for baseline therapy to fail may unnecessarily delay adequate control.
Summary
Clinicians should always look at the patient’s problem more deeply and beyond the boundaries of standard protocols.
Cardiovascular risk includes metabolic risk, and overcoming this burden often requires more therapeutic interventions than those explicitly listed in standard treatment algorithms. Only an integrated cardiometabolic approach can improve blood pressure control, reduce residual risk, and meaningfully improve long-term outcomes and quality of life.