Cardio 4 Flashcards
What is the distribution of SBP in a population?
Unimodal with a skew towards upper values
What are the variants that determine blood pressure?
Genetics (50%) and environmental (50%)
What are the features of rare coding variants?
1 in 2000, affect coding sequence (2% of DNA that codes for protein structure) – a variant in this code stops normal protein function, 5mmHg
What are the features of common non-coding variants?
1 in 3, alter non-coding parts of the genome, DNA involved with when and where the proteins are expressed, differentiates one cell from another,
Is the sequence of DNA or its expression immutable? Why/why not?
Sequence of DNA is immutable but expression is not - epigenetics
What is SBP at the start of life?
60 mmHg
What happens at the point where people split to develop a higher or lower BP?
Specific genes relative to blood pressure are expressed
Is there a correlation between parental and personal BP?
Yes, but not all people follow this trend
What was a feature of renin levels in the high high and low low groups (parental and personal BP)?
High high had high renin and low low had lowest plasma renin
What was a feature of the renal arteries in people with high BP?
High renal vascular resistance
What are the features of the SHR?
Kidney function diminished - low GFR, high plasma renin, high BP
What is a treatment to stop BP increasing later in life?
Perindopril - drops BP early in life and even after treatment stops BP is kept low
What is the action of perindopril?
Blocks RAS system by inhibiting Ang II
What are some effective forms of RAS inhibition?
ACE inhibitor, Ang I receptor antagonists, Ang 1 receptors antisense cDNA, renin antibodies
What is the problem with calcium channel blockers and vasodilators?
Dropped BP during treatment but after treatment stopped the effects diminished
When is action on BP most effective?
Puberty
What is the feature of the milan rats?
Didn’t respond to BP treatment early in life - no effect later in life
What happens if you transplant an untreated kidney into a treated animal?
BP rises to the high level it would have reached without treatment
What are the long term physiological mechanisms of perindopril?
vascular structure (more supple CV system), sympathetic NS (rest internal set point), reduced angiotensinogen, renal function (lower renal vascular resistance and higher renal blood flow)
What are the features of the TROPHY study?
772 participants, prehypertension, average 48 years, 2 years of treatment with angiotensin receptor blocker, during treatment - rates of hypertension were reduced - but study wasn’t followed through so unsure if it was a lifetime effect
