Blood Pressure: Causes of Hypertension

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The surplus of salt in our modern day diet makes many of us vulnerable to hypertension in old age. Nearly 1 in 4 Canadians past the age of 20 suffers from hypertension, with the risk significantly increasing with age. Consequently, chronic hypertension is a global public health burden that attributes to secondary morbidities of cardiovascular and kidney diseases. 

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Lifestyle, specifically heavy consumption of salty foods, older age, and genetic susceptibility are key determining factors of hypertension. However, there is high variation in the susceptibility and prevalence of hypertension across different ethnic and population groups. Moreover, genetic variation in genes that control salt retention and blood vessel tone are predicted to be contribute to hypertension risk.

A simple evolutionary explanation for the present-day high prevalence of hypertension is the mismatch between our ancestral susceptibility to sodium scarcity and our modern day environment where salt is overabundant in out diet. The thrifty genotype hypothesis by James Neel suggests natural selection has favored “thrifty” genes that improved survival and reproductive success, the definition of fitness in evolutionary biology, and these genes are often associated with conserving nutritional resources in times of scarcity. In the face of our modern environment, these ancestral “thrifty” genetic variants that conferred a fitness advantage can have previously unobserved maladaptive effects on our health and possibly leading to metabolic syndromes.

The “sodium retention” hypothesis illustrates the “thrifty” hypothesis in the context of hypertension, where sodium-conserving genes that benefited our ancestors during salt scarcity are now maladaptive in modern times. This is supported with evidence of frequency variation in genetic alleles that regulate blood pressure among ethnic groups and high frequency of heat-adapted genetic variants in populations from low latitudes and hot, wet climates. Ancestral African environment was characterized by hot, wet climate and salt scarcity and adaptation was maximized for heat regulation, sodium retention, and blood vessel tone reactivity to achieve blood pressure homeostasis. If genes originally selected for sodium conservation alters the set point to a higher blood pressure range when expressed in an environment of sodium abundance as in our current environment, individuals harboring these genotypes are at increased risk of developing hypertension.

Interestingly, Young et al  extended this theory by claiming that the variation in susceptibility to hypertension across different populations results from the differential selection pressure 50-10,000 years ago during when humans migrated out of Africa. The authors present evidence of a variant of the gene GNB3, a gene involved in blood pressure regulation as an adaptive response to heat, that may account for a major variation in hypertension across the global population. Populations from hot, wet climates were more susceptible to hypertension than populations from colder climates. This study found that latitude and genetic allele GNB3 C825T explain the major variation in hypertension prevalence across different ethnic groups. In addition, higher C825T allele frequency was correlated with higher prevalence of hypertension. Furthermore, this allele was most frequently occurring in populations of African descent where climate was hot.

Despite the global endemic of hypertension, the prevalence of this common disease varies considerably across different populations. Natural selection influenced blood pressure regulation in ethnically and geographically diverse populations that led to differential susceptibility to hypertension. Evidence presented by Young et al and others highlights the potential impact evolutionary factors could have on the implementation of precision medicine in hypertension. Understanding and appreciating genetic variability within and between diverse populations based on ancestral roots can improve the prevention and treatment for hypertension.  

29 April 2022

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