Lecture 20: Blood Pressure and Cholesterol Flashcards
what are modifiable risk factors for CVD?
high blood pressure and cholesterol are very important modifiable risk factors for CVD
- in 1990 ranked #1
- in 2019 ranked #3
how is cholesterol involved in atherosclerosis?
- key component of many cardiovascular disease
- atherosclerosis develops through the deposition of fatty matirial on the vessel wall, which is mainly cholesterol.
how is cholesterol associated with coronary heart disease?
diet and genes combined with high serum cholesterol is associated with a high risk of CHD
what are the different types of lipoproteins? how does this related to serum cholesterol?
serum cholesterol travels in lipoproteins as they are hydrophobic
types of lipoproteins:
- Very low-density lipoprotein (VLDL-cholesterol
- Low-density lipoprotein (LDL-cholesterol)
- High-density lipoprotein (HDL-cholesterol)
what is familial hypercholestrolemia?
people with familial hypercholestrolemia develop atherosclerosis very early in life
- genetic makeup is very important for small amount of people
- tend to develop atherosclerosis at a much younger age
- if someone is healthy, atherosclerosis with develop over the 4th decade, and so by the 8th decade there will be a CVD event.
what was found in the coronary disease among united states soliders killed in action in korea study?
- people without a strong genetic predisposition may develop atherosclerosis in the 4th decade
- we know that it can develop in early adulthood
- 300 autopsies were performed, average age was 22. (18-42 range)
- found evidence of coronary arteriosclerosis
- even in those without a genetic predisposition, atherosclerosis develops much earlier than expected. this is much younger than the age medication is normally given.
what is shown here?
- relationship between serum cholesterol and CHD mortality at a country level (ecological level data)
- e.g. Finland have a high serum cholesterol and deaths in the country while other countries like velika krisna has low serum cholesterol and CHD mortality
what does this show?
early findings of the framingham study
- measured serum cholesterol and found that in the rate of arteriosclerotic heart disease/1000 there is a dose response.
lower serum cholesterol = lower response
arteriosclerotic heart disease = myocardial infarction, angina, or sudden death attributable to coronary heart disease
what is this?
a normal distribution
- the people who developed CHD had higher serum cholesterol than those who did not develop CHD
- however there is an overlap between the distributions which indicates that other factors are involved
what was the serum lipids a nd CVD prospective studies collaboration?
- cohort study
- enrolled people without CVD
- followed them up over years
- 12 million person years at risk between 40-89 years old (900,000 population)
what does this show?
- shows data about serum cholesterol
- relationship between usual total cholesterol and hazard ratios (relative risk) for IHD mortality
- stratified by age
- shows that as people get older, risk of IHD mortality increases regardless of total cholesterol level
- in each age band, the higher cholesterol = higher risk of dying from IHD
- demonstrates that several risk factors are important (age+total cholesterol)
- there is a linear association between normal cholesterol and IHD mortality and there is no cut off point/threshold.
what does this show?
the relationship between the serum lipids and hazard ratio for IHD mortality
A) high HDL cholesterol = lower risk (all age groups)
B) high non-HDL cholesterol = higher risk
C) high total HDL cholesterol = higher risk
- total HDL cholesterol is used to look at CVD risk with cholesterol
what is used to predict risk of morality from IHD?
total/HDL cholesterol ratio was the strongest predictor of IHD mortality and more than twice as informative as total cholesterol
what was the aim of the INTERHEART Case control study?
effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries
what were the findings of the INTERHEART case control study?
total cholesterol over HDL cholesterol
- shows that the higher ratio of LDL cholesterol to HDL is associated with greater odds of myocardial infarction
what does this show?
- there is very little difference in odds ratio of myocardial infarction due to LDL/HDL ratio by region
- universal association across all populations in the world
- this is called “little heterogeniety by region”
what sorts of RCTs/Intervention studies have there been for cholesterol lowering treatment?
“efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins
what were the results of this study?
primary outcome = death from various causes
CHD - treamtment with statins was associated with a reduction in CHD mortality by 90%. CI doesnt include null (true effect)
Stroke - 9% decreased (combined both types of stroke)
total mortality was also reduced with statins use
statins lowered cholesterol lowered mortality by CVD and other CV causes
what does this tell us about the RCT study?
- there was little heterogeneity by presence or absence or level of other risk factors
- gives confidence that this is a real effect.
was is the trend of total cholesterol in high income countries? why might this be?
decline in total cholesterol in high income countries
likely to be due to medication (statins) and dietary change
what does this show?
trends in mean cholesterol in the UK
in 1989-1999 affluent and deprived population
cholesterol levels have decreased over time
- coincides with statins coming into effect in the 1990s
what does this show?
serum total cholestrol changes in new zealand by age group
- increasing until men and women get into their 50’s, then we see a decline
- statins are not normally prescribed until over 50 so we can see this come into effect for the over 50 group, but the increase in the younger ages must be due to other factors
what are the 2 types of blood pressure?
systolic and diastolic
what is hypertension?
elevated blood pressure
- but elevated blood pressure is a better wording for hypertension
what is normal blood pressure?
120/80mmHg
what is prehypertension?
120-139/80-89mmHg
what is stage 1 and stage 2 hypertension?
stage 1: 140-159/90-99 mmHg
stage 2: ≥160/≥100 mmHg
140/90mmHg is the cut off point of diagnosing someone with hypertension
how was blood pressure thought of in the past?
in the early 20th century, elevated BP was thought to be a normal part of ageing, although ‘malignant hypertension’ was recognised
- the Framingham study was the first to show associated between BP and CVD
what does this show?
results from the framginham heart study
- Arteriosclerotic heart disease looked at a graded description of BP. Suggested a dose-response between blood pressure and risk of arteriosclerotic heart disease
(ASHD = MI, angina or suddent death attributable to CHD)
what were the findings of RCTs involving early therapy?
earliest RCTs had a placebo
- most early studies were done in men and had treatments targeted for men and male hormones
- people with hugely elevated diastolic BP (115mmhHg+) were involved in the study (90mmHg was the threshold)
what were the findings of the RCT?
placebo group = dotted line
solid line = active treatment group
over 60 months, the active treatment group has reduced cumulative rate of stroke
placebo group also reduced, but not as much as active treatment group
what does this show?
linear association between systolic and diastolic blood pressure and mortality from stroke
- there are also effects due to age
- there is no threshold for this though!!!
what does this show?
linear associated between usual BP and mortality for IHD mortality
- differences among age
- no threshold!!!
what was involved in the systolic blood pressure intervention trial (SPRINT)
- RCT
- 9361 US participants with systolic BP ≥130mmHg and increased cardiovascular disease without diabetes (population)
intervention: intensive treatment (aim <120 mmHg SBP)
control: standard treatment (aim <140mmHg SBP)
outcome: myocardial infarction, acute coronary syndromes, stroke, heart failure or CV death
Time: stopped early 3.26 years due to clinical equipoise
what does this show?
the intervention of active treatment was able to lower systolic BP to the intended target on 120mmHg.
what were the results of the SPRINT study?
- primary outcome (a composite of myocardial infarction, acute coronary syndrome, stroke, heart failure, or death from cardiovascular causes): Hazard ratio with intensive treatment 0.75 (95% 0.64-0.89)
- death any cause: Hazard ratio with intensive treatment 0.73 (95% CI 0.60-0.90)
what does this show?
little heterogeneity by presence or absence or level of other risk factors
intensive treatment was better across all other risk factors
what is important to consider about the SPRINT trial?
if BP is too low in old people, it can lead to fainting and falls
can have problems without other adverse effects
people have other things going on, not just CVD risk or BP
need to consider and monitor adverse effects
what were the findings of the NZ health survey in 2016/17
- 6% of adults aged 15+ years reported a diagnosis of hypertension (634000 adults)
- 3% has measured blood pressure >140/90mmHg
the mean SBP was 124mmHg
what is the population paradox?
“a large number of people at small risk may give rise to more cases of disease than the small number who are at high risk”
how does the population paradox work in relation to BP?
there are so many people in the larger group, so the greatest number of CV events happen here.
greatest number of events occurs in the larger group with lower risk
can deal with his using the high risk strategy or population strategy
what is the high risk strategy?
can give people in very high risk group medication and push them into lower risk category.
this makes a major difference to people in the high risk group, but doesn’t reduce the rate of CV events, as most of the events occur in the normal population with more people in it.
what is a population strategy?
can do something to the sick population that shifts the whole population distribution. this produces the greatest reduction in CVD events across the whole population
what are the strengths of a high risk strategy?
- intervention seems appropriate to the individual
- avoids interfering with those with no excess risk
- readily accommodated within medical ethos
- benefit-to-risk ratio, cost-to-benefit ratio maxmised
what are the limitations of high risk strategy?
- success is palliative, doesn’t remedy the situation
- hard to sustain behaviour change
- contribution to overall disease may be small
what are the strengths of a population strategy?
- reduction in overall burden of disease is large
- environmental change doesn’t require individual behaviour change
what are the limitations of population strategy?
- intervention targets those with those with minimal excess risk
- not readily accommodated within medical ethos
- benefit-to-risk ratio, cost-to-benefit ratio smaller
- environmental change requires ‘buy in’ from multiple stakeholders (e.g. food industry, tobacco industry)
