Observed genes

Polygenic score

Influential genes: WNT2B,LSP1,CACNA1D

WNT2B gene plays a role in various developmental and cellular processes and variations in this gene have been associated with hypertension.

The LSP1 gene is involved in immune system regulation and inflammation. Some studies have suggested a possible connection between this gene and hypertension.

The CACNA1D gene encodes a subunit of a calcium channel that plays a role in regulating blood vessel function and blood pressure.

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Overview

Arterial hypertension, often referred to as hypertension or elevated blood pressure, is a common condition in which there is chronically increased blood pressure in the vascular system. The vascular system delivers the blood from the heart to all parts of the body. With each beat the heart pumps blood into the vessels. Blood pressure is created by the force of blood pushing against the walls of blood vessels (arteries) as it is pumped by the heart. The higher the pressure is, the harder the heart has to pump. (2)

The pressure in the vasculature and in the individual cardiac compartments depends on three factors:

1. the strength of the cardiac contractions
2. the resistance of the vasculature
3. the current blood volume

Blood pressure (BP) is measured in millimeters of mercury (mm Hg). It is shown using 2 values, one over the other. A pressure of 120 to 80 mm of the mercury column is stated as optimal. The first value corresponds to the systolic pressure (the pressure that occurs during the cardiac contraction) and it is the highest pressure the heart is able to produce. The second value represents the diastolic pressure, which is the pressure in the arteries when the heart rests between beats and fills with blood. 

It is important to note that the blood pressure varies with age, which is due to the elasticity of the arterial wall. Elasticity of the arterial wall of older people is impaired and it is therefore less able to absorb the force of the blood pressure wave during systole (cardiac contraction), which is reflected in an increase in systolic blood pressure.

There are two types of high blood pressure:

• Primary (essential) hypertension - the cause of primary or essential hypertension is high cannot be determined. Primary hypertension affects 90-95% of people who have high blood pressure.
• Secondary hypertension - Secondary hypertension or symptomatic hypertension is caused by an underlying condition. It affects 5-10% of people who have high blood pressure. Secondary hypertension can be caused by a variety of different diseases and factors, such as:

• Kidney disease
• Adrenal gland tumors
• Thyroid gland problems
• Hypertension in pregnancy
• Hypertension in sleep apnoea syndrome
• Certain medications - such as birth control pills, cold remedies, decongestants, over-the-counter pain relievers and some prescription drugs
• Illegal drugs, such as cocaine, amphetamines and other psychostimulants

Although high blood pressure remains most common in adults, more children are becoming at risk. It can be caused by diseases of the kidneys or heart but for a growing number, poor lifestyle habits — such as an unhealthy diet, lack of exercise and exposure to alcohol in young age — contribute to an increase in their blood pressure. (1)

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Prevalence & Risk factors

According to WHO, hypertension is a major cause of premature death globally, with upwards of 1 in 4 men and 1 in 5 women (therefore over a billion people) having the condition, especially in low and middle-income countries, where about two thirds of cases are found. This is most probably due to the increase of risk factors in those populations in recent decades. (2)

A person is more prone to develop hypertension in presence of several risk factors:

• Higher age
• Gender - men up to 64 years of age are more prone to developing the condition, after that the risk is higher for women
• Family history of hypertension, premature CVD, hypercholesterolemia, diabetes
• Personal history of cardiovascular disease (CVD) - myocardial infarction, heart failure, stroke, transient ischemic attacks, diabetes, dyslipidemia, chronic kidney disease 
• Smoking status - both smoking and/or chewing tobacco
• Poor diet - high salt intake, minimum of vegetables and fruits, high fat intake
• High alcohol intake
• Lack of physical activity
• Being overweight or obese
• Stress

Genetics

In most studies, a positive family history is a frequent feature in hypertensive patients, with the heritability (fraction of the trait explained by genes) estimated to vary between 35 and 50%. However, hypertension is a highly heterogeneous condition with a multifactorial set of causes. Several studies of the genome have identified over 120 loci (positions on a chromosome where a particular gene is located) that are associated with BP regulation, but together these only explain about 3.5% of the trait variance. (4)

According to recent studies, the genetic contribution to BP regulation is of two completely different types:

• Polygenic type of inheritance – There are possibly many thousands of common genetic risk variants that are individually associated with small effects (approximately 1 mmHg or even less). The likelihood of primary hypertension increases with the number of risk variants present and is modulated by the above mentioned risk factors such as age, gender and alcohol intake. Consequently, primary hypertension cannot be caused by one or only a few genetic variants. Also, there is no such thing as the primary hypertension gene. (3, 5)
• Monogenic type of inheritance – The increase in blood pressure is caused by a deviation in one gene. This type of inheritance occurs only in a few of the rarer forms of secondary hypertension. Those rare gene mutations running in families can cause secondary hypertension, even in the absence of other risk factors. (3, 5)

1. Liddle syndrome
2. Severe autosomal dominant hypertension and brachydactyly
3. Glucocorticoid-suppressible hyperaldosteronism
4. Apparent mineralocorticoid excess

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Signs & Symptoms

It is common for symptoms to go unnoticed for a long time, and many people are therefore unaware that there is infact a problem. 

Common symptoms are: 

• headaches
• nosebleeds
• arrhythmias (irregular heart rhythms)
• changes in vision
• buzzing in the ears
• fatigue
• vomiting and nausea
• anxiety
• chest pain
• confusion
• muscle tremors 

If the hypertension is untreated, it can lead to angina (persistent chest pain), heart attacks, aneurysms of vessels, heart failure and severe arrhythmias, which can cause a sudden death. It can also cause strokes (by damaging arteries that deliver oxygen to the brain), kidney damage (often leading to chronic kidney failure), damage to blood vessels of the eyes (causing vision loss), troubles with memory and/or dementia. (2)

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Diagnosis

According to most guidelines, it is recommended to diagnose hypertension when a person’s systolic blood pressure in the office or clinic is ≥ 140 mm Hg and/or their diastolic blood pressure is ≥ 90 mm Hg after repeated testing. If possible, the diagnosis should not be made in one office visit, because blood pressure normally varies during the day and may increase during a doctor visit (also referred to as white coat hypertension). To confirm a diagnosis of hypertension, 2-3 visits at intervals of 1-4 weeks (depending on the level of blood pressure) are usually necessary. The diagnosis can be made in a single visit if the pressure is ≥180/110 mm Hg and there is evidence of cardiovascular disease (CVD). (4)

The patient can be also asked to record their blood pressure at home to get more information and confirm the diagnosis. A Holter device can be also used to do so. A Holter blood pressure device is worn by the patient for twenty-four hours and records the changes in blood pressure over a 24-hour period in the normal environment and activities of the patient outside the doctor’s office. 

In addition to confirming the diagnosis, home monitoring also allows the doctor to check whether the blood pressure treatment is working or to diagnose a worsening of the condition. (1, 2)

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Therapy

Changing your lifestyle can help control and manage high blood pressure, however sometimes those adjustments are not effective enough and medication is needed. The type of prescribed medication depends on the measured values and the overall health of the patient. Very often two or more types of drugs are combined because they work better than one. (1)

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Prevention

The best way to prevent hypertension and associated diseases of the heart, brain, kidney and other organs is by reducing modifiable risk factors and therefore:

• Maintaining an ideal body weight
• Including regular physical activity
• Limiting the alcohol intake
• Giving up smoking
• Limiting caffeine intake
• Healthy diet - plenty of fruit and vegetables, minimum of salt intake, reducing total fat intake, especially saturated fat
• Reducing and managing mental stress (2)

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Prognosis

The prognosis depends on the level of BP (especially systolic), the presence of other risk factors (smoking, elevated blood lipids, diabetes, obesity), organ damage and the presence of associated diseases. Studies have shown that lowering systolic blood pressure by 10 mmHg or diastolic blood pressure by 5 mmHg leads to a reduction in major cardiovascular events by approximately 20% and all-cause mortality by approximately 10-15%.

In determining overall cardiovascular risk, it is recommended to use the SCORE nomograms to predict the probability of cardiovascular death over the next 10 years.

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Recommendations

• If you are overweight, try to lose weight. Even a small weight loss can be beneficial. Reducing weight by just 3% to 5% can help decrease certain fats in the blood, lower blood sugar and reduce the risk of type 2 diabetes
• Choose a diet rich in fruits, vegetables, and low-fat dairy products, and low in meats, sweets, and refined grains
• Eat less salt (sodium). It will lower the excess fluid in your body as well as your blood pressure and also allow your medicines to work properly
• Try to be active for at least 30 minutes a day
• Limit the amount of alcohol you drink
• Stop smoking

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