The Secret of "H"-type Hypertension
Seeing this title, you might wonder: we’ve all heard of primary and secondary hypertension, but what exactly is "H"-type hypertension? Just how close is it to us?
In fact, "H"-type hypertension is a newly defined concept from 2010. It’s called "H"-type because this form of hypertension is closely related to a substance in the body—homocysteine (Hcy).
A large body of research has now confirmed that elevated serum homocysteine is an independent risk factor for cardiovascular and cerebrovascular diseases such as coronary heart disease and stroke. Patients with primary hypertension whose serum homocysteine levels exceed 10 μmol/L are defined as having "H"-type hypertension. Therefore, "H"-type hypertension still falls under the category of primary hypertension.
So where does homocysteine come from, and what role does it play? Let’s take a look at its origin story.
Homocysteine is a sulfur-containing amino acid derived from methionine in the diet. It is an intermediate product of methionine metabolism in almost all tissues of the body and provides methyl groups for various substances. Homocysteine is eventually broken down and transformed via the transsulfuration pathway and remethylation pathway. Its physiological function is to maintain the balance of sulfur-containing amino acids in the body.
There are many reasons for elevated homocysteine levels, primarily the following:
1. Excessive intake of methionine (i.e., excessive consumption of animal protein);
2. Folate, vitamin B12, and B6 are crucial coenzymes in the metabolism, breakdown, or conversion of homocysteine. Insufficient intake or deficiency due to certain diseases can lead to increased homocysteine levels;
3. Diseases: such as hypothyroidism and renal insufficiency;
4. Genetic factors.
The above explanation of homocysteine may seem a bit abstract. Here's an imperfect analogy to help understand: Methionine is like a real estate developer—the most essential and scarce resource in real estate development is land. When land becomes scarce after repeated development, property prices—i.e., homocysteine levels—rise. And when these soaring prices exceed the purchasing power and expectations of buyers—folate, vitamin B12, and B6—fewer people can afford it, leading to poor sales and metabolism. The result is a backlog that causes harm.
Elevated homocysteine can damage vascular endothelial cells and vascular smooth muscle cells, ultimately leading to lipid deposition in the vessel walls, causing or accelerating the onset and progression of atherosclerosis. Since hypertension itself also leads to these vascular changes, patients with "H"-type hypertension face a "double" risk, increasing the likelihood of cardiovascular and cerebrovascular events.
In China, the incidence of stroke is significantly higher than in other countries, one reason being hyperhomocysteinemia (HHcy), and another important factor being that about 75% of hypertensive patients in China have elevated Hcy levels—91% in men and 63% in women. In other words, most hypertension cases in China carry a "double" cardiovascular risk that damages our blood vessels, and hypertension combined with high homocysteine is the most critical risk factor for stroke. But why is that?
First, this is related to the fact that most hypertension in China is of the MTHFR C677T genotype. This MTHFR C677T polymorphism is characterized by a high prevalence of hypertension, elevated plasma HCY, and severe atherosclerosis. Another important reason is the general lack of folate—a crucial nutrient—in the Chinese diet. A review published in The Lancet states: long-term use of folic acid significantly reduces the risk of stroke by 18%. The longer the treatment, the more homocysteine drops to a certain level, and the better the effect is in populations not receiving food folate fortification (which matches the characteristics of the Chinese population). Folate is particularly effective in the primary prevention of stroke. Its efficacy in secondary prevention remains to be proven①. Therefore, actively managing "H"-type hypertension has become a consensus among experts in stroke prevention and treatment, and actively supplementing folic acid is a key part of this approach.
Therefore, we recommend that hypertensive patients include homocysteine testing as a routine check-up item, just as important as lipid and glucose tests, to better prevent and control the disease.
References: ①Wang et al. Lancet 2007; 369:1876-82