Risk Factors for Atherosclerosis Flashcards
What does it mean for something to a positive risk factor?
- it increases the likeliness of something occurring
- adding to the probablity
What are 6 modifiable positive risk factors?
- dyslipidemia
- hypertension
- diabetes
- physical inactivity
- obesity
- smoking
What does it mean for something negative risk factor?
- it decreases the likeliness of something occuring
- subtracts from the probability
What is an example of a modifiable negative risk factor?
high HDL >60mg/dl (protective)
What are 4 non-modifiable risk factors?
- older age
- gender
- race
- family history of CAD
Non-modifiable risk factor
Older age
- male > 45
- female > 55
Non-modifiable risk factor
Gender
male
Non-modifiable risk factor
Race
african american, hispanic
Non-modifiable risk factor
Family History of CAD
- father or brother with CAD < 55
- mother or sister with CAD < 65
Modifiable Risk Factors
Dyslipidemia: Total Cholesterol
greater than 240 mg/dl
(high risk)
Modifiable Risk Factors
Dyslipidemia: LDL
greater than 160 mg/dl
(high risk)
Modifiable Risk Factors
Dyslipidemia: HDL
less than 40 mg/dl
(high risk)
Describe th MRFIT Trial.
- multicenter trial of CVD risk factor reduction in middle-aged men (35-57)
- no CVD at baseline
- measured age, smoking status, blood pressure and serum cholesterol
- followed for 6 years
MRFIT Trial
How many deaths out of 7840 were due to CVD?
2626
MRFIT Trial
Less than 20th percentile = baseline risk (less than 181 mg/dl)
- reference group
MRFIT Trial
Greater than 20th percentile (182 - 202 mg/dl)
associtaed with 30% increased risk of CVD death
MRFIT Trial
Greater than or equal to 80th percentile (greater/equal 246 mg/dl)
associated with 340% increase in CVD death
MRFIT Trial
Greater than or equal to 90th percentile (greater/equal 264 mg/dl)
associated with 400% increase in CVD death rate
Define relative risk
the risk of a certian event happening in one group versus another
Put relative risk into a sentence.
The risk of developing a disease after an exposure vs. the risk of developing a disease in absence of the exposure.
Treatment of dyslipidemia
HMG-CoA Reductase Inhibitors
“statins”
HMG-CoA Reductase Inhibitors
Mechanism of action: blocks the conversion of HMG-CoA to ?? in ?? pathway.
- melavonic acid
- cholesterol biosynthesis
HMG-CoA Reductase Inhibitors
Reduction of… (3)
- Total cholesterol
- LDL
- triglycerides
HMG-CoA Reductase Inhibitors
Increases in…
HDL
HMG-CoA Reductase Inhibitors
On average, treatment results in ??% reduction in ??, ??, and ??.
- 20-33%
- MI, stroke, and CV death
HMG-CoA Reductase Inhibitors
Key Point?
- 1/2 of all myocardial infarctions ocur in individuals with normal cholesterol levels
- certain values don’t confirm heart disease
Treatment of Dyslipidemia
Primary Prevention Trials
no history of CAD when started on statin drug
Treatment of Dyslipidemia
Secondary prevention trials
previous MI and high TC and LDL when started on statin drug
Describe the CARE Trial (1998)
- secondary prevention trial
- patients with normal baseline total cholesterol and LDL
- started on statin after myocardial infarction
CARE Trial
LDL results
lowered about 32%
CARE Trial
HDL results
increased about 5%
CARE Trial
Overall results
reduced nonfatal or fatal MI by 24%
CARE Trial
CARE conclusion
statin therapy reduced risk of MI and death in CAD patients with normal TC and LDL
Possible mechanisms of Statin reduction function
Limits ?? production of ?? cholesterol.
- liver
- LDL
Possible mechanisms of Statin reduction function
Increases ?? of ?? from blood.
- clearance
- LDL
Possible mechanisms of Statin reduction function
Stabilizes athersclerotic plaque by either:
- ??
- ??
- reducing lipid core of plaque
- reducing proteases (MMPs) that degrade fibrous cap
Possible mechanisms of Statin reduction function
Increases endothelial function:
- increases ?? and ?? production
- decreases ?? production = prevents degradation of ??
- eNOS and NO
- ROS and NO
MRFIT
Hypertension: Optimal BP
less than 120 / less than 80
MRFIT
Hypertension: normal but not optimal
120-129 / 80-84
MRFIT
Hypertension: High Normal
130-139 / 85-89
MRFIT
Hypertension: Stage 1 HTN
140-159 / 90-99
MRFIT
Hypertension: Stage 2/3 HTN
greater than 160 / 100
MRFIT
HTN Goal?
To compare relationships of systolic BP, diastolic BP, and pulse pressure (PP) separately and jointly with CVD mortality
MRFIT HTN/CAD Results
In men age 35-44 (young), CVD risk was greatest for those with…
both systolic HTN and diastolic HTN; compared to one alone
MRFIT HTN/CAD Results
In men 45-57 (middle-aged), CVD risk was greatest for men with either:
- ??
- ??
- systolic HTN and diastolic HTN
- systolic HTN and DBP less than 80 (highest risk group)
MRFIT HTN/CAD Results
Conclusion?
Systolic HTN and low diastolic BP were highest risk in middle aged adults; with systolic/diastolic HTN being the next highest risk
Framingham Heart Study: Temporal change in BP over time
- Mean, systolic and diastolic BP….
increase slowly until mid-life (age 50-60).
Framingham Heart Study: Temporal change in BP over time
2.Only systolic BP continually…
increases in a linear fashion after mid-life.
Framingham Heart Study: Temporal change in BP over time
3.Diastolic BP ?? at mid-life and begins…
- plateaus
to decline thereafter.
Framingham Heart Study: Temporal change in BP over time
4.Mean BP ?? at mid-life and remains…
thru lifespan.
Framingham Heart Study: Temporal change in BP over time
5.Pulse Pressure …..
increases exponentially beyond mid-life.
Framingham Heart Study: Take home points
Adults less than 50 yrs of age, ?? is the strongest predictor of CVD risk.
diastolic BP
Framingham Heart Study: Take home points
?? and ?? were the strongest predictors of CVD in adults over 60 yrs.
Systolic BP and PP
(PP was superior)
Framingham Heart Study: Take home points
?? becomes inversely related with CVD risk over the age of 60.
Diastolic BP
New High BP Guidelines
HTN Stage 1
130-139 / 80-89
New High BP Guidelines
HTN Stage 2
greater than 140 / greater than 90
HTN Treatment
If the risk is less than 10%….
start with healthy lifestyle recommendations and reasses in 3-6 months
HTN Treatment
If risk is greater than 10% or the patient hase known CVD, diabetes mellitus, or chronic kidney disease…
recommended lifestyle changes and BP-lowering medication
New HTN BP Guidelines
Non-Pharmacological treatment options
- healthy diet
- weight loss
- sodium (reduce intake)
- PA (add aerobic exercises)
- PA (add dynamic resistance training)
- alcohol (reduce intake)
Diabetes Mellitus
ADA Definition
(at least 1 of 3)
- fasting blood glucose: >126 mg/dl
- oral glucose tolerance test: glucose >200 2 hrs after 75g
- HbA > 6.4%
Diabetes mellitus
ADA Prediabetes
- FBG: 100 - 126
- OGTT: 140 - 199 2 hrs after 75g
- HbA = 5.7 - 6.4%
Diabetes Mellitus
Type 1
insulin-dependent
- pancreatic beta-cells fail to produce insulin
- exogenous insulin required
Diabetes Mellitus
Type 2
non-insulin dependent
- Insulin resistance: tissues (muscle, fat, liver) do not respond (less sensitive) to insulin’s effects to lower glucose
- results in over production of insulin
Diabetes and CAD risk
KEY POINT?
in general, adults with diabetes are 2-4 times increased risk of developing CAD and stroke
Diabetes and CAD risk
incidence of 1st MI
5.5 - 6x higher rate of 1st MI for diabetics
Diabetes and CAD risk
incidence of 2nd MI
about 2.5 higher rate of 2nd MI in diabetics
MRFIT PA
Describe MRFIT PA.
1st US study to document decreased risk of CAD, CAD death, and all-cause death with increased PA
- no CAD, but several risk factors at baseline
- based on self-reported amount of leisure-time physical activity (LTPA) by questionnaire
MRFIT PA
1 = low LTPA
- avg 15 min/day
- 73 kcal/day
MRFIT PA
2 = moderate LTPA
- avg 47 min/day
- 223 kcal/day
MRFIT PA
3 = high LTPA
- 133 min/day
- 638 kcal/day
MRFIT PA
In regards to group 2 and group 3….
there is no statistical difference between the two
MRFIT PA Results
Moderate and high LTPA were associated with:
- ??
- ??
- 63% less fatal CAD deaths
- 70% less all-cause deaths
compared to low LTPA
MRFIT PA
Conclusions:
1. LTPA has a ?? to CAD and overall mortality in high-risk men
2. ?? was just as good as ?? in reducing CHD (MI), CHD death, and all-cause death.
- modest inverse relation
- Moderate LTPA, high intensity LTPA
Obesity using BMI
Overweight BMI?
25 - 29.9
Obesity using BMI
Obese I BMI?
Obesity class?
- 30 - 34.0
- class I
Obesity using BMI
Obese II BMI?
Obesity class?
- 35 - 39.9
- class II
Obesity using BMI
Morbidly Obese BMI?
Obesity class?
- greater than 40
- class III
Obesity using BMI
How is BMI calculated?
BMI = weight / height
Obesity and CVD mortality
results?
- death rates increased throughout the range of increasing BMI from 24.9
- risk of CVD death increased rapidly with BMIs greater than 30
- low BMI (less than 18.5) predictive of increased CVD and all cause death
Obesity/Physical Fitness and CAD death
Fit or Fat key point??
“Lean and unfit” has double the risk compared to “high fit and obese”
- PA is more important than BMI
Obesity/Physical Fitness and CAD death
Fit or Fat Conclusions:
Low fitness…
was an independent predictor of CAD death and all-cause death in all BMI groups.
Obesity/Physical Fitness and CAD death
Fit or Fat Conclusions:
High fitness…
reduced risk of CAD death and all-cause death compared to low-fitness in each BMI group
Obesity/Physical Fitness and CAD death
Fit or Fat Overall Conclusion.
better to be fit and fat, than thin and unfit
Smoking
How many people in US are estimated to smoke?
42.1 million
- 18.1% of all adults 18 and older
Smoking
Is smoking more common among men or women?
men (20.5%) compared to women (15.8%)
Smoking
What is the current population trend?
overall decrease in smoking prevalance from 2005 (20.9%) to 2012 (18.1%)
Smoking Cessation and MI risk
In adults with no previous CHD, the reduction in cardiac event rate is associated with smoking cessation ranges from…
7 to 47 percent
Smoking Cessation and MI risk
In adults with no previous CHD, the risks of MI diminish relatively soon after smoking cesstion by…
1 year compared with smokers
Smoking Cessation and MI risk
In adults with no previous CHD, Relative Risk back to level of never smokers beyond…
1 year (2+ years)
Smoking
What are the 7 potential mechanisms of by which smoking promotes CVD?
- enhacned oxidation of lipids - atherosclerosis
- decreased HDL-C
- increased platelet adhesiveness
- excessive stimulation of sympathetic nervous system
- increased propensity for thrombosis
- increased vasospasm/constriction of coronary arteries
- O2 replaced by CO on RBCs - tissue ischemia
Framingham Risk Score
What does the framingham risk score NOT predict?
stroke of heart failure
Framingham Risk Score
What does the framingham risk score predict?
estimates 10 year risk of CAD in person without diabetes or existing heart disease
Framingham Risk Score
Low risk?
10% or less
Framingham Risk Score
Moderate risk?
10 - 19%
Framingham Risk Score
High risk?
20% or more
Framingham Risk Score
CAD equivalent?
diseases that have 10-year high risk of CAD (20% or more)
- diabetes, chronic kidney disease, carotid artery disease
Metabolic Syndrome
Define Metabolic Syndrome
a clustering of CAD risk factors most notable abdominal obesity, insulin resistance, high BP, increasing the risk of CAD and type 2 diabetes
Metabolic Syndrome
How is Metabolic Syndrome diagnosed?
3 or more of the following:
- glucose intolerance
- abdominal obesity
- hypertension
- high fasting triglycerides
- low fasting HDL-C
Metabolic Syndrome: possible sign
Glucose intolerance (pre-diabetes)
fasting glucose > 100 mg/dl
Metabolic Syndrome: possible sign
Abdominal obesity: waist circumference
- men > 40 inches
- womens > 35 inches
Metabolic Syndrome: possible sign
Hypertension
greater than 130 / greater than 80 mmHg
Metabolic Syndrome: possible sign
High fasting triglycerides
greater than 150 mg/dl
Metabolic Syndrome: possible sign
low fasting HDL-C
- men < 40 mg/dl
- women < 50 mg/dl
Metabolic Syndrome Prevalence
Total in US
23.7%
Metabolic Syndrome Prevalance
In regards to age?
increases with age
- greater than 45% in age 60+ years
Metabolic Syndrome Prevalance
In regards to gender?
no difference between men and women
Metabolic Syndrome Prevalance
In regards to race?
higher in hispanic women
Metabolic Syndrome
Does a diagnosis of MetS increase CVD risk compared to each CVD risk factor individually?
unclear; could possibly be due to cluster effect
Metabolic Syndrome
Does diagnosis of MetS alter course of medical treatment?
unclear; not usually