Genetics, Lifestyle Factors Effects On Hypertension And Non-pharmacologic Management

Question 1

What is the mosaic of BP

Answer 1

BP can be affected by:
Haemodynamics
Humoral
Intrauterine programming
Endocrine system
Neural system
Adaptive
Anatomical
Renal system
Environment
Genetics

Question 2

Genetic determinants of hypertension

Answer 2

Twin studies show 30-50% of variation of blood pressure is due to genetics

New studies suggest hypertension is polygenic

There are a few rare Mendelian forms of hypertension

GWAS showed >901 loci affecting BP associated with a combine 10.4 mmHg higher SBP
- individual variants identified only explain 1mmHg/allele for SBP and 0.5mmHg/allele for DBP

Question 3

Lifestyle Factors for Uncomplicated Hypertension

Answer 3

Aging
Obesity and insulin resistance
High salt diet
Low potassium diet
Sedentariness
Stress

Question 4

How does Aging affect risk of Hypertension

Answer 4

Normally aorta cushions pulsatile SBP due to elastin in intima-medial wall
- as you age, elastin is replaced by collagen causing arterial stiffness and widening of pulse pressure (diff b/w SBP and DBP increases)
- after mid 50s, SBP increases and DBP plateaus or decreases —> more at risk for isolated systolic hypertension

Question 5

How does Obesity and insulin resistance increase risk of Hypertension
- MOA

Answer 5

-Every 10% increase in weight is associated with an increase of 6.5mmHg SBP
- obesity and weight gain account for 25% of all hypertension
- is the most common cause of adolescent HT

MOA:
1) Increased plasma volume and CO
2) RAAS activation including activation of mineralcorticoid receptors
3) shifting of pressure natriuresis to a higher BP threshold in obesity
4) sympathetic nervous system activation

Question 6

Sedentariness and Exercise and relation to hypertension risk

Answer 6

Associated with increased incident hypertension and mortality
>4 hours a day of screen time with hyperinsulinemia even among those physically active
- chronic, unbroken periods of muscular unloading causes suppression of SK. Muscle lipoprotein lipase activity (necessary for HDL production) and reduced glucose uptake
- taking breaks was beneficially associated with decreased waist circumference, body mass index, and 2-h plasma glucose

Question 7

Dietary Sodium intake and relation to Hypertension

Answer 7

HT doesn’t usually occur in societies with very low Na consumption
- global mean Na intake was 3.95g/day (10g/day salt)
- Canada’s guideline is 2g/day and 1tsp salt = 5mg
75% of daily Na intake comes from processed foods and restaurants

Question 8

Sodium Sensitivity

Answer 8

Extend of BP change after abrupt changes in salt intake vary considerably from one individual to another (as well as in the same individual if tested at different times)

Salt sensitivity increases with age and is more prominent in African Americans, obese people and patients with metabolic syndrome or chronic kidney disease

Impaired renal sodium excretion can lead to initial volume expansion and then hypertension

Question 9

Dietary Potassium Intake and Relation to HT
MOA

Answer 9

BP is inversely related to Potassium intake

Low intake (<40 med/day (or 1.5g/day or 120mmol/day))
- average consumption is <70-80 molecules/day in most countries due to food processing and lack of fruits and veggies

Increased potassium decreased SBP by 3.5mmHg and DBP by 1.95mmHg and there is a protective effect against stroke

MOA:
- sodium excretion is diminished by hypokalemia via increases of sodium reabsorption —> low potassium increases NCC expression and causes increased reabsorption of Na

Question 10

Stress and its effects of HT

Answer 10

• significantly related to hypertension
• Siegrist’s model as (1) high imbalance, a combination of high effort and low reward at work or (2) high over-commitment, and exhaustive work-related coping style indexing the inability to unwind showed high imbalance but not over-commitment was associated with increased SBP

Work hypertension is called MASKED Hypertension

Question 11

Masked Hypertension

Answer 11

Work hypertension caused by high imbalance causing increased SBP

Question 12

Alcohol relation to HT
MOA

Answer 12

Excessive intake is related to development of HT
> 2 drinks/day have a 1.5-2fold increase in HT
Dose-related and especially when intake is >5 drinks/day
MOA:
- stimulation of SNS, RAAS, raised cortisol levels, inhibition of nitric oxide

Question 13

Other causes of Hypertension

Answer 13

Stimulants - cocaine and amphetamines
Decongestants - pseudophedrine
Prednisone
Oral contraceptive pills
Some anti-depressants - TCA’s and SSRIs
NSAIDs
Supplements - St. John’s Wort, Ephedra, Ginko, Ginseng

Question 14

Health Behaviour change to treat Hypertension

Answer 14

Physical exercise - 30-60 moderate intensity dynamic exercise 4-7 days per week

Weight reduction - BMI between 18.5-24.9 and waist circumference <102cm men and <88cm women

Alcohol consumption (two or less per day; Men <14/week; Women <9/week

Diet (DASH diet - emphasis on fruits, veggies, low fat dairy, fibre, whole grains, protein from plant sources low in saturated fat, high calcium, magnesium and potassium)

Sodium reduction towards 2000mg/day (5g salt)

Stress management via CBT and relaxation techniques

Smoking cessation and smoke-free environment

Potassium Supplementation

Question 15

How does exercise reduce risk of developing HT?

Answer 15

Exercise training increases endothelial production of NO synthase, decreases aortic stiffness and increases whole-body insulin sensitivity

Also reduces circulating NE and vascular resistance and hyperinsulinemia

Question 16

OSA-CPAP relation to cardiovascular disease and BP

Answer 16

Showed now difference in cardiovascular outcome but improved daytime sleepiness and QoL

Showed improvements in BP lowering diastolic BP by 5mmHg