Clinical Aspects of Cardiovascular Risk Flashcards
Most common cause of premature death?
Coronary Heart Disease - particularly in men
How does deprivation affect CVD risk?
Increased deprivation causes increased CVD risk
Reasons why CHD is the leading cause of death in the world?
Increased in no. of older people
Changes in underlying health habits, such as: Increase in smoking Dietary changes - increased cholesterol Sedentary lifestyle Rises in BP
Medical care focus on treatment rather than prevention
What is atherosclerosis?
Progressive disease characterised by plaque build-up within the arteries, which can partially/totally block the blood flow through as artery
Constituents of atherosclerotic plaque?
Formed from fatty substances, like cholesterol, cellular waste, calcium and fibrin. There is also inflammatory cell build-up
Complications of atherosclerotic plaque?
Bleeding into the plaque
Formation of a clot on the surface of the clot
If either happens and blocks the artery, an MI or stroke may result
Steps in atherosclerotic pathway?
Endothelial damage
Protective response - results in production of cellular adhesion molecules, such as cytokines, chemokines and growth factors
Monocytes and T lymphocytes attach to “sticky” surface of endothelial cells
Migrate through arterial wall to sub-endothelial space
Monocytes differentiate into macrophages take up oxidised LDL-C
Lipid-rich foam cells form the fatty streak and plaque
Causes of endothelial damage?
Haemodynamic forces (shear stress caused by e.g: hypertension)
Vasoactive substances
Mediators (cytokines) from blood cells
Cigarette smoke
Atherogenic diet
Elevated glucose levels
Oxidised LDL-C
What is atherothrombosis?
Formation of an acute thrombus in a vessel affected by atherosclerosis
Progression of atherothrombosis?
Initiated by changes in the vessel wall resulting from plaque disruption
Atherosclerotic plaque can become unstable and rupture, exposing components such as collagen to allow platelets to adhere to the damaged area and initiate thrombus formation
Thrombus can extend and occlude the vessel, leading to ischaemia and tissue injury
Risk factors for CVD?
Age Family history and ethnicity Hypertension Heart disease Diabetes Smoking Obesity Unhealthy diet (atherogenic) Oral contraception Previous strokes/TIA Binge drinking and substance abuse Inactivity
Modifiable risk factors for CVD?
Smoking Dyslipidaemia: raised LDL, low HDL or raised triglycerides Raised BP Diabetes mellitus Obesity Dietary factors Thrombogenic factors Lack of exercise Excess alcohol consumption
?Deprivation
Non-modifiable risk factors for CVD?
Personal history of CHD
Family history of CHD
Age
Gender
5 major classes of lipoproteins and functions?
Chylomicrons (largest) - synthesised in the gut after a fatty meal; transport dietary triglycerides from the gut to the sites of use and storage and are cleared rapidly from the bloodstream
VLDL (smaller than chylomicrons) - produced in the liver and are main carriers of endogenous (synthesised in the liver) triglycerides and cholesterol to sites of use/storage
IDL - formed during VLDL and chylomicron breakdown; involved in recycling of cholesterol by the liver, as well as formation of LDL in the blood. Also, implicated in atherogenesis
LDL - principal lipoproteins involved in atherosclerosis; OXIDISED LDL is the MOST ATHEROGENIC FORM as they are the main carriers of cholesterol
HDL (smallest) - return cholesterol from peripheral tissue to the liver, for excretion; protective against atherosclerosis
General rule for function of lipoproteins related to their size?
Smaller VLDL, IDL and LDL are all atherogenic
Large VLDL and chylomicrons are not
HDL carries cholesterol away from the arterial wall and is protective
LDL is more strongly associated with CHD events in which gender?
Males
Describe triglyceride involvement with CHD?
Increased risk of CHD events - may be related to low HDL levels and highly atherogenic forms of LDL cholesterol
Factors that lower HDL levels?
Smoking
Obesity
Physical inactivity
What do statins achieve?
Reduce CHD end points, by reducing total and LDL cholesterol
Other actions: Improvement of endothelial dysfunction Increased NO bioavailability Anti-oxidant properties Inhibition of inflammatory responses Stabilisation of atherosclerotic plaques
Why does familial hyperlipidaemia tend to occur?
Endogenous problem: genetic fault with LDL receptors
What is xanthelasma?
Xanthomas of eyelids, may or may not be associated with hyperlipidaemia
Are fatty depositis
What are tendon xanthomas?
Diffuse infiltration of tendon by lipids, e.g: extensor tendons of fingers, elbows, Achilles tendon (on of the MOST COMMON sites)
What are tuberous xanthomas?
Lipid deposits in the dermis and subcutis; can be papuler, nodular or plaques
Located on extensor surfaces of large joints, hands, buttocks, heels and flexures
What are eruptive xanthomas?
Small reddish-rellow papules on buttocks, posterior thighs of body folds
Tends to be associated with HIGH TRIGLYCERIDE LEVELS
Diseases attributable to hypertension?
Heart failure Left ventricular hypertrophy MI Hypertensive encephalopathy CHD Cerebral haemmorhage Stroke Chronic Kidney Failure Blindness Aortic aneurysm Gangrene of the lower extremities
Types of hypertension?
Essential hypertension - no underlying cause (90% of causes)
Secondary hypertension - underlying cause
Hypertension treatment reduces?
Ischaemic heart disease
Stroke
Mortality
Lifestyle modification?
Lose weight, if overweight Limit alcohol intake Increase physical activity Reduce salt intake Stop smoking Limit intake of foods rich in fats and cholesterol
Other risk factors that hypertensives have?
A large majority of hypertensive patients have other CV risk factors: Dyslipidaemia Diabetes Age Male gender Smoking Family history
Greatest drop in BP is seen when?
With combination of BP lowering medications
Reasons why type 2 diabetes mellitus predisposes to CVD?
It is associated with hypertension, abnormalities in lipoprotein metabolism and increased propensity to oxidative stress and endothelial dysfunction
Hyperglycaemia may accelerate vascular damage
Type 2 diabetes is also a hyper-coagulable state, with enhanced coagulation, decreased fibrinolysis and platelet aggregability
What is the “ticking clock” hypothesis?
There are microvascular complication at onset of hyperglycaemia
There are macrovascular complications before the diagnosis of hyperglycaemia (pre-diabetes)
What is the cornerstone of treatment?
Diet
Calorie intake to normalise weight
Plus or minus an exercise program
Obesity increased risks of what events/issues?
Stroke Angina MI Hypertension Type 2 diabetes - risk of this with obese women is higher than for obese men
What is the metabolic syndrome?
Metabolic syndrome is the medical term for a combination of hypercholesterolaemia/dyslipidaemia, diabetes, high blood pressure and obesity
What is CRP and hs-CRP?
CRP - a non-specific, but very sensitive, inflammatory marker tested all the time
Ethnic differences with CHD death rates?
South Asians living in the UK have a higher death rate - higher in women than men
Black Caribbean and Black Africans have a much lower CHD death rate than is average (lower in women than in men) - but much higher risk of stroke
How to calculate CVD risk?
Assign score which takes into account: Current age Sex SCOTTISH postcode Family history Diabetes Cigarettes smoked daily Systolic BP Total cholesterol HDL cholesterol
What happens when risk factors co-exist?
For most CHD patients, they have multiple risk factors - when they co-exist, the sum of theit combined effect is much greater than the sum of their individual effects
What is involved when, with treatment, ischaemia is the target?
Antianginal Medications:
Calcium Blockers
Nitrates
Beta Blockers
Revascularization:
Angioplasty
CABG
Risk factor modification
What is involved when, with treatment, atherothrombosis is the target?
Aspirin Statin Beta Blocker ACE Inhibitor Exercise Smoking Cessation
Symptom control:
Antianginal medications
Revascularization (smaller participation)
