Module 10: Hypertension and Kidney Disease Flashcards
1
Q
Management of ____ has been one of the success stories leading to the decline in morbidity and mortality of CVD
A
hypertension
2
Q
Hypertension is a significant risk factor for
A
- CVD
- CAD
- congestive heart failure
- renal failure
- peripheral vascular disease
- dementia
- atrial fibrillation
3
Q
Describe the systolic and diastolic BP for the European Society of Hypertension Classification of Blood Pressure:
- Optimal
- Normal
- High-normal
- Grade 1 (mild hypertension)
- Grade 2 (moderate hypertension)
- Grade 3 (severe hypertension)
- Isolated Systolic Hypertension (ISH)
A
- Optimal: <120 and/or <80
- Normal <130 and/or <85
- High-normal: 130-139 and/or 85-89
- Grade 1 (mild hypertension): 140-159 and/or 90-99
- Grade 2 (moderate hypertension): 160-179 and/or 100-109
- Grade 3 (severe hypertension): >/ 180 and/or >/110
- Isolated Systolic Hypertension (ISH): >/140 and <90
4
Q
Describe the systolic and diastolic BP for the JNC (American) Classification of Blood Pressure
- Optimal
- Normal
- High-normal
- Stage 1 (mild hypertension)
- Stage 2 (moderate to severe hypertension)
- Isolated Systolic Hypertension (ISH)
A
- Optimal: <120 and/or <80
- Normal <130 and/or <85
- High-normal: 130-139 and/or 85-89
- Stage 1 (mild hypertension): 140-159 and/or 90-99
- Stage 2 (moderate to severe hypertension): >/160 and/or >/100-109
- Isolated Systolic Hypertension (ISH): >/140 and <90
5
Q
What is MRFIT
A
Multiple Risk Factor Intervention Trial
6
Q
Determined from a cohort of 347 978 men screened for the Multiple Risk Factor Intervention Trial (MRFIT) and followed for an average of 12 yrs, is SBP or DBP a stronger predictor of death from CAD?
A
SBP
7
Q
Describe the Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease
A
Background:
Info limited regarding the risk of CVD in persons with high normal BP (SBP of 130-139 mm Hg, DBP of 85-89 mm Hg, or both).
Conclusions:
High-normal BP is associated with an inc risk of CVD. Our findings emphasize the need to determine whether lowering high-normal BP can reduce the risk of CVD
8
Q
Describe the auscultatory method
A
a
9
Q
What is the most common method to measure BP?
A
oscillometric method
10
Q
What is the oscillometric method
A
uses an electronic sensor to detect blood flow
11
Q
Describe the steps to use the oscillometric method
A
- The cuff is inflated to a pressure initially in excess of the systolic arterial pressure, and then reduces to below diastolic pressure over a period of about 30 secs
- The values of systolic and diastolic pressure are computed, not actually measured from the raw data, using an algorithm; the computed results are displayed.
12
Q
During what 2 occasions in the oscillometric method is the cuff pressure essentially constant
A
When blood flow is nil (cuff pressure exceeding systolic pressure) or unimpeded (cuff pressure below diastolic pressure)
13
Q
What happens to the cuff pressure when BF is present?
A
When blood flow is present, but restricted, the cuff pressure, which is monitored by the pressure sensor, will vary periodically in synchrony with the cyclic expansion and contraction of the brachial artery, i.e., it will OSCILLATE.
14
Q
Most automatic blood pressure cuffs use _____ method.
A
oscillometric
15
Q
almost all clinical studies looking at the prognosis value of hypertension and treatment outcomes use the _____ methodology
A
auscultatory
16
Q
Oscillometric monitors may produce inaccurate readings in patients with what kind of heart and circulation problems
A
- atherosclerosis
- arrhythmia
- pre-eclampsia
- pulsus alternans
- pulsus paradoxus
17
Q
Because different oscillometric BP cuffs may have different readings, what must be done?
A
Therefore, it is important to calibrate these automatic BP machine’s readings with the auscultatory method.
18
Q
What is the most accurate way of measuring blood pressure?
A
put a catheter into the artery and measure the pressure with a pressure transducer
19
Q
Problem with measuring BP using a catheter and pressure transducer?
A
invasive procedure and is usually reserved for patients requiring careful and instantaneous monitoring of blood pressure
20
Q
It is increasingly recognized that B{ recorded in the ambulatory setting is more accurate in determining outcomes. How to measure BP outside of a healthcare professional’s office?
A
Either a 24-hour ambulatory BP recording device or the patients can use a home device. As these devices use oscillometric methodology to measure blood pressure, it is important to calibrate these devices against the auscultatory methodology.
21
Q
In patients without diabetes, hypertension is defined by the Canadian Hypertension Society and the UK National Institute for Health and Clinical Excellence as
A
greater than 140/90
22
Q
The classification of BP is based on how many measurements?
A
the average of two or more properly measured BP values from two or more clinical encounters
23
Q
Patients with high blood pressure and the following conditions are considered to have hypertension urgency/emergency and should be sent to the emergency room for evaluation:
A
- Systolic BP>200 diastolic BP>130
- Accelerated or malignant hypertension with papilledema
- Hypertensive encephalopathy
- Intracranial or subarachnoid hemorrhage
- Acute aortic dissection
- Acute refractory LV failure
- Renal crises from collagen vascular disease
- Pheochromocytoma
- Rebound hypertension from cessation of clonidine
- Eclampsia (rare but serious condition where high BP results in seizures during pregnancy)
- Severe hypertension in patients requiring emergency surgery
- Severe epistaxis
24
Q
In patients with diabetes, the threshold for diagnosis is set at what BP?
A
lower at 130/80
25
Up to __% of diabetic patients die of CVD
80%
26
Most patients with _____ have hypertension
diabetes
27
Between ___ and ___ % of diabetic complications have been attributed to hypertension.
35 and 75%
28
Treatment of hypertension in patients with diabetes reduces
total mortality, myocardial infarction, stroke, retinopathy and progressive renal failure rates
29
More intensive reduction in blood pressure reduces major cardiovascular events and total mortality by ___
25%
30
Reversible risks for developing hypertension are (4)
1. Obesity
2. Poor dietary habits
3. High sodium intake
4. Sedentary lifestyle
5. High alcohol consumption
31
Incidence of hypertension in those identified with high normal blood pressure are as follows:***
772 subjects, mean age 48.5
Not receiving treatment for hypertension
Average of 3 blood pressures at baseline:
SBP 130-139 and DBP < 89 OR
SBP < 139 and DBP 85-89
primary endpoint – new onset hypertension
New onset hypertension: (first of any one of the following):
BP > 140/90 at any of 3 visits or
SBP > 160 or DBP > 100
BP requires drug treatment
140/90 at month 48
32
What are the six Canadian Hypertension Society Guidelines for the diagnosis of hypertension
1. Section I: Assess BP at all appropriate visits
2. Section II: Criteria for Diagnosis of Hypertension and recommendations for Follow-Up
3. Section III: Assessment of Overall Cardiovascular Risk
4. Section IV: Routine Laboratory Tests
5. Section V: Home BP Measurement
6. Section VI: Ambulatory BP Measurement
33
Describe Section I: Assess blood pressure at all appropriate visits. Why should this be done?
BP of all adults should be measured whenever it is appropriate by healthcare professionals using standardized techniques.
- To screen for hypertension
- To assess CV risk
- To monitor antihypertensive treatment
34
Describe Section II: Criteria for the diagnosis of hypertension and recommendations for follow-up.
**Patients with high normal blood pressure (clinic SBP 130-139 and/or DBP 85-89) should be followed annually
1. A patient who has elevated BP either by a) out of the office BP measurement or b) in the office BP measurement should go conduct a hypertension visit #1
2. During the hypertension visit #1, the physician will perform a BP measurement, History and Physical examination. Patients demonstrating hypertensive urgency or emergency should be diagnosed as hypertensive and require immediate management. If SBP is 140 mmHg or higher and/or DBP is 90 mmHg or higher, diagnostic tests should be ordered and visit 2 scheduled within 1 month. If BP is high normal (SBP 130 mmHg to 139 mmHg and/or DBP 85 mmHg to 89 mmHg), annual follow-up is recommended
3. At visit 2, patients with target organ damage, diabetes, or chronic kidney disease (CKD) can be diagnosed as hypertensive if SBP is >/140 mmHg and/or DBP is >/90 mmHg OR if SBP is >/180 mmHg and/or the DBP is >/110 mmHg. Patients without these conditions but have SBP 140-179 or DBP 90-109 should undergo further evaluation using any of the three approaches outlined below:
1. Clinic BPM: During hypertension visit 3, if averaged SBP >/160 mmHg or DBP >/100, the patient will be diagnosed at hypertensive.
- If SBP is <160 or DBP < 100, either conduct a ABPM or HBPM, or come back for visit 4-5.
- During visit 4-5, if averaged SBP >/140 mmHg or DBP >/90 mmHg, diagnose at HTN. If <140 or <90, continue to follow up
2. Ambulatory BP measurement (ABPM): Using ABPM, patients diagnosed as hypertensive if the mean awake SBP is >/ 135 mmHg or DBP >/85 mmHg, or if the mean 24 h SBP is >/130 mmHg or DBP >/80 mmHg. If awake BP <135/85 and 24 hour <130/80, then continue to follow up.
3. Home BP measurement: Patients diagnosed as hypertensive if average SBP is >/ 135 mmHg or DBP is >/85. If the average home BP <135/85, it is advisable to perform 24 h ABPM to confirm that the mean 24 h ABPM is <130/80 mmHg and the mean awake ABPM is <135/85 mmHg before diagnosing white coat hypertension.
4. After the diagnosis of hypertension, patients will receive nonpharmacological treatment (e.g. lifestyle modification), with or without pharmacological treatment. Then determine whether BP readings are below target during 2 consecutive visits. If they are, follow up at 3-6 month intervals. If BP readings are not below target during the 2 consecutive visits, determine whether patient has symptoms, severe hypertension, intolerance to anti-hypertensive treatment, or target organ damage. If patient has any of such things, they need more frequent visits. If they do not, they should have visits every 1-2 months. Regardless of whether the patient experiences such reactions, consider home based BP measurement in hypertension management, to assess for presence of masked hypertension or white coat effect and to enhance adherence. Once the target BP has been reached, patients should be seen at 3-6 month intervals.
35
Draw a diagram to describe the concept of masked hypertension
Label Masked HTN, True hypertensive, True normotensive, White coat HTN.
36
Prevalence of masked hypertension is approximately ____% in the general population but is higher in patients with ___.
- 10%
| - diabetes
37
Describe the GENERAL SECTIONS in Section III: Assessment of the overall CV risk
1. Search for target organ damage:
2. Search for exogenous potentially modifiable factors that can induce/aggravate hypertension
3. Treat Hypertension in the Context of Overall CV Risk
4. CV Risk Factors that may alter thresholds and targets in the treatment of HTN; Presence of Risk Factors
5. Presence of Target Organ Damage
6. Presence of atherosclerotic vascular disease
7. Method of Risk Assessment
8. SCORE 10 years Fatal Cardiovascular - Risk Evaluation in Canada
9. SCORE Canada: Relative Risk Evaluation for use in those less than 40 years old
11. Factors to take into account when using SCORE Canada Caveats to estimating Fatal CVD Risk
38
In Section III: Assessment of the overall CV risk, describe Search for target organ damage:
1. Search for target organ damage:
- CVD:
- > transient ischemic attacks
- > ischemic or hemorrhagic stroke
- > vascular dementia
- Hypertensive retinopathy
- Left ventricular dysfunction
- Left ventricular hypertrophy
- Coronary artery disease
- > myocardial infarction
- > angina pectoris
- > congestive heart failure
- Chronic kidney disease
- > hypertensive nephropathy (GFR < 60 ml/min/1.73 m2)
- > albuminuria
- Peripheral artery disease
- > intermittent claudication
- > ankle brachial index <9
39
In Section III: Assessment of the overall CV risk, describe Search for exogenous potentially modifiable factors that can induce/aggravate hypertension
Prescription Drugs:
- NSAIDs, including COXIBS (e.g. celecoxib)
- Corticosteroids and anabolic steroids
- Oral contraceptive and sex hormones
- Vasoconstricting/sympathomimetic decongestants
- Calcineurin inhibitors (cyclosporin, tacrolimus)
- Erythropoietin and analogues
- Monoamine oxidase inhibitors (MAOIs)
- Other sympathomemetics e.g. Midodrine
Other:
- Licorice root
- Stimulants including cocaine
- Salt
- Excessive alcohol use
- Sleep apnea
Over 90% of hypertensive Canadians have other CV risks
Assess and manage hypertensive patients for dyslipidemia, dysglycemia (e.g. impaired fasting glucose, diabetes) abdominal obesity, unhealthy eating and physical inactivity
40
In Section III: Assessment of the overall CV risk, describe Treat Hypertension in the Context of Overall Cardiovascular Risk
- Overall CV risk should be assessed. In hypertensive patients, consider using calculations that include cerebrovascular events.
- In the absence of Canadian data to determine the accuracy of risk calculations, avoid using absolute levels of risk to support treatment decisions at specific risk thresholds.
- Simply counting risk factors may underestimate risk.
41
In Section III: Assessment of the overall CV risk, describe CV Risk Factors that may alter thresholds and targets in the treatment of HTN; Presence of Risk Factors
- Increasing age
- Male gender
- Smoking
- Family history of premature cardiovascular disease (age< 55 in men and < 65 in women)
- Dyslipidemia
- Sedentary lifestyle
- Unhealthy eating
- Abdominal obesity
- Dysglycemia (diabetes, impaired glucose tolerance, impaired fasting glucose)
42
In Section III: Assessment of the overall CV risk, describe Presence of Target Organ Damage
- Microalbuminuria or proteinuria
- Left ventricular hypertrophy
- Chronic kidney disease (glomerular filtration rate < 60 ml/min/1.73 m2)
43
In Section III: Assessment of the overall CV risk, describe Presence of atherosclerotic vascular disease
- Previous stroke or TIA
- Coronary HD
- Peripheral arterial disease
44
In Section III: Assessment of the overall CV risk, describe Method of Risk Assessment
- Clinical impression
- Risk factor counting
- Risk calculation or equation tools
- Framingham (CHD) - https://www.mdcalc.com/framingham-coronary-heart-disease-risk-score (Links to an external site.)
- SCORE Canada – Systematic Cerebrovascular and Coronary Risk Evaluation scorecanada.ca
- Cardiovascular AgeTM myhealthcheckup.com
- Doctors using clinical intuition are unable to accurately estimate absolute coronary risk;
- Clinical impression identifies ‘high-risk’ patients 70% of the time, with an overall trend to greater underestimation of risk due to inappropriate application of tables.
- Risk factor counting has low sensitivity for identifying patients at high risk; many high-risk patients will not be treated.
- Objective risk scores are provided.
45
In Section III: Assessment of the overall CV risk, describe SCORE 10 years Fatal Cardiovascular - Risk Evaluation in Canada
This chart is an example of a method for estimating the risk of cardiovascular events in patients. Other tools are available and many are based on the Framingham Study. CHEP has not endorsed any specific method of assessing cardiovascular risk.
The SCORE charts calculate 10-year risk of fatal CVD, coronary and cerebrovascular. As the chart predicts fatal CV events, the threshold for being at HIGH risk is defined as ≥5%. The chart can also be used to estimate the effect of changes from one risk category to another (e.g. when a person stops smoking).
46
What is the threshold for being at HIGH risk in the SCORE?
≥5%
47
What factors does the SCORE Canada take into account?
1. Age
2. Sex
3. Smoking status
4. SBP
5. Total-Chol/ HDL-C Ratio
48
In Section III: Assessment of the overall CV risk, describe SCORE Canada: Relative Risk Evaluation for use in those less than 40 years old
Relative risk evaluation chart may be used in those under age 40 in whom absolute risk assessments are not as meaningful. The chart can be used to show younger people at low total risk that, relative to others in their age group, their risk may be many times higher than necessary. This may be helpful to motivate decisions about avoidance of smoking, healthy nutrition and exercise, as well as flagging those who may become candidates to medication. Other relative risk assessments are available and one computerized version estimates cardiovascular age and can also be used to motivate younger patients with cardiovascular risks factors. Relative risk chart uses Total Cholesterol.
49
In Section III: Assessment of the overall CV risk, describe SCORE Canada Caveats to estimating Fatal CVD Risk
- Person approaches next age category.
- Pre-clinical evidence of atherosclerosis (CT scan, ultrasonography, …).
- Strong family history of premature CVD: Multiply risk by 1.4.
- Obesity; BMI > 30 kg/m2, ; Waist circumference > 102 cm (men) and > 88 cm (woman).
- Sedentary lifestyle.
- Diabetes: multiply risk by 2 for men and by 4 for women.
- Raised serum triglycerides level.
- Raised level of C-reactive protein, Fibrinogen, Homocysteine, Apolipoprotein B or Lp(a).
- Total Fatal CVD Risk may be higher than indicated in the standard chart in many patients.
- Use these qualifiers to modulate Total Fatal CVD Risk.
- The charts should also be used in the light of the clinician’s knowledge and judgment, especially with regard to local conditions.
50
Describe the GENERAL SECTIONS in 4.Section IV: Routine Laboratory Tests
1. Preliminary Investigations of patients with hypertension
2. Follow-up investigations of patients with hypertension
3. Optional Laboratory Tests - Investigation in specific patient subgroups
51
In 4.Section IV: Routine Laboratory Tests, describe Preliminary Investigations of patients with hypertension
- Urinalysis
- Blood chemistry (potassium, sodium and creatinine)
- Fasting glucose
- Fasting total cholesterol and high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), triglycerides
- Standard 12-leads ECG
Currently there is insufficient evidence to recommend routine testing of microalbuminuria in people with hypertension who do not have diabetes
52
Is there sufficient evidence to recommend routine testing of microalbuminuria in people with hypertension who do not have diabetes
No
53
In 4.Section IV: Routine Laboratory Tests, describe Follow-up investigations of patients with hypertension
- During the maintenance phase of hypertension management, tests (including electrolytes, creatinine, glucose, and fasting lipids) should be repeated with a frequency reflecting the clinical situation.
- Diabetes develops in 1-3%/year of those with drug treated hypertension. The risk is higher in those treated with a diuretic or beta blocker, in the obese, sedentary, with higher fasting glucose and who have unhealthy eating patterns. Assess for diabetes more frequently in these patients.
54
How does antihypertensive drugs affect the risk of diabetes?
Diabetes develops in 1-3%/year of those with drug treated hypertension. The risk is higher in those treated with a diuretic or beta blocker, in the obese, sedentary, with higher fasting glucose and who have unhealthy eating patterns. Assess for diabetes more frequently in these patients.
55
In 4.Section IV: Routine Laboratory Tests, describe Optional Laboratory Tests - Investigation in specific patient subgroups
- For those with diabetes or CKD: assess urinary albumin excretion, since therapeutic recommendations differ if proteinuria is present.
- For those suspected of having an endocrine cause for the high BP, or renovascular hypertension, see following slides.
- Other secondary forms of hypertension require specific testing.
56
Describe the GENERAL SECTIONS in Describe the GENERAL SECTIONS in 5.Section V: Home measurement of blood pressure
1. Home BP measurement should be encouraged to increase patient involvement in care. Which patients?
2. Potential advantages of home blood pressure measurement
3. Note that not all patients are suited to home measurements. These patients could be patients with:
4. Suggested protocol for home measurement of blood pressure for the diagnosis of hypertens
5. Home Measurement of BP: Patient Education
6. Web-based home monitoring
7. Home measurement: Doing it right
EQUIPMENT, PREPARATION, DO and DON'T
8. Home Measurement of BP: Confirm contradictory home measurement readings
57
In 5.Section V: Home measurement of blood pressure, Home BP measurement should be encouraged to increase patient involvement in care. Which patients? What BP should be considered elevated?
- Uncomplicated hypertension
- Suspected non adherence
- Office-induced blood pressure elevation (white coat effect)
- Masked hypertension
* * Average BP > 135/85 mm Hg should be considered elevated.
58
In 5.Section V: Home measurement of blood pressure, what are the Potential advantages of home blood pressure measurement
- More rapid confirmation of the diagnosis of hypertension
- Improved ability to predict CV prognosis
- Improved BP control
- Can be used to assess patients for white coat hypertension (WCH) and masked hypertension
- Reduced medication use in some (WCH)
- Improved adherence to drug therapy
59
In 5.Section V: Home measurement of blood pressure, not all patients are suited to home measurements. These patients could be patients with:
- Undue anxiety in response to high BP readings
- Physical or mental disability prevents accurate technique or recording
- Arm not suited to BP cuff (e.g. conical shaped arm)
- Irregular pulse or arrhythmias prevent accurate readings
- Lack of interest
60
In 5.Section V: Home measurement of blood pressure, what is the Suggested protocol for home measurement of blood pressure for the diagnosis of hypertension?
- Home BP values should be based on:
1. duplicate measures
2. morning and evening
3. for an initial 7-day period.
- First day home BP values should not be considered.
- The following 6 days BP readings should be averaged
- Average BP equal to or over 135/85 mmHg should be considered elevated.
- The target BPs for patients with diabetes or CKD have not been established by CHEP.
61
In 5.Section V: Home measurement of blood pressure, home Measurement of BP: Patient Education
- Assist patients select a model with the correct size of cuff
- Measure and record the patients mid arm circumference so they can match it to cuff size.
- Recommend devices listed at https://hypertension.ca/ or marked with this symbol
- Ask patients to carefully follow the instructions with device and to record only those blood pressures where they have followed recommended procedure
- Advise patients that average readings equal to or over 135/85 mmHg are high
- In patients with diabetes or chronic kidney disease, lower therapeutic targets and diagnostic criteria are likely required
- Home measurement can help to improve patient adherence
62
In 5.Section V: Home measurement of blood pressure, Web-based home monitoring
Website resources are available heartandstroke.ca/bp (Links to an external site.)Links to an external site.
Individualized automated counseling and tracking to assist patients home monitor and to enhance self-management of lifestyle for home monitoring
Hypertension Canada Guidelines
Information to assist you in training patients to measure blood pressure at home
Brief action tool for Health Care professionals under resources in the Education tools for health care professionals section
Information for patients on how to purchase a device for home measurement and how to measure blood pressure at home
Learn how to measure your blood pressure at home and Home measurement of blood pressure under resources in the Education tools for health care professionals section).
In 2009, a training DVD on home measurement of blood pressure will become available for download here:
Advice for patients on when to contact health care professional based on home blood pressure readings.
63
What is the Advice for patients on when to contact health care professional based on home blood pressure readings.
a) Systolic BP (mmHg)
Less than 130
Diastolic BP reading
Less than 85
b) 130-179*
85-109*
c) 180 – 199*
110-119
d) More than 200*
More than 120
```
a) Systolic BP (mmHg)
Less than 130
Diastolic BP reading
Less than 85
=> Usual follow-up
```
b) 130-179*
85-109*
=> Check reading again using the correct technique. If the readings remain high, discuss with your healthcare provider at your next regularly scheduled appointment
c) 180 – 199*
110-119
=> Check reading again using the correct technique. If the readings remain high, discuss with your healthcare provider at your next regularly scheduled appointment
d) More than 200*
More than 120
=> Check reading again using the correct technique. If the readings remain high, discuss with your healthcare provider at your next regularly scheduled appointment
64
In 5.Section V: Home measurement of blood pressure, Home measurement: Doing it right EQUIPMENT. What steps should be done to ensure equipment is right?
1. Validated device
2. Look for the Hypertension Canada logo or go to www.hypertension.ca for a list of validated devices available in Canada
3. Ensure the cuff size is appropriate
4. Ensure the device is accurate in the patient at purchase and annually
65
In 5.Section V: Home measurement of blood pressure, what are the preparation DO's?
1. Read and carefully follow the instructions provided with the device
2. Relax in a comfortable chair with back support for 5 minutes
3. Sit quietly without talking or distractions (e.g. TV)
4. Put the cuff on a bare arm or one with a light sleeve
5. Support the arm on a table so it is at heart level
6. Record 2 readings in the morning and evening daily for seven days (discarding the first days readings) to help diagnose hypertension
7. Measure and record your blood pressure (as above) for several days before an appointment with a health care professional
8. Posters and handouts providing recommendations to patients on how to measure blood pressure can be found at www.hypertension.ca
9. (Learn how to measure your blood pressure at home and Home measurement of blood pressure in the Education tools for health care professionals section)
10. Validated device
11. Look for the logo or go to www.hypertension.ca/chs for a list of validated devices available in Canada
12. Ensure the cuff size is appropriate
13. Ensure the device is accurate in the patient at purchase and annually
66
In 5.Section V: Home measurement of blood pressure, what are the preparation DON'T's?
1. Measure if stressed, cold, in pain or if your bowel or bladder are uncomfortable
2. Measure within 1 hour of heavy physical activity
3. Measure within 30 minutes of smoking or drinking coffee
67
In 5.Section V: Home measurement of blood pressure, Home Measurement of BP: Confirm contradictory home measurement readings. What should you do if office BP measurement is elevated and home BP is normal or vice versa?
Consider further assess using 24 h ambulatory BP monitoring
68
Describe the GENERAL SECTIONS in 6.Section VI: Ambulatory BP Monitoring
1. Which patients?
2. How to?
3. Clinic, Home, Ambulatory (ABP) Blood Pressure Measurement: Equivalence Numbers
4. Follow Up Algorithm for High Blood Pressure: Using Ambulatory Blood Pressure Measurement
5. Usual blood pressure threshold values for initiation of pharmacological treatment
6. Indications for Pharmacotherapy
7. Blood pressure target values for treatment of hypertension
69
6.Section VI: Ambulatory BP Monitoring. Beyond the diagnosis of hypertension, ABPM measurement may also be considered for selected patients for the management of HTN. Which patients?
1. Untreated
- Mild (Grade 1) to moderate (Grade 2) clinic BP elevation and without target organ damage.
2. Treated patients
- BP that is not below target values despite receiving appropriate antihypertensive therapy.
- Symptoms suggestive of hypotension.
- Fluctuating office BP readings.
70
6.Section VI: Ambulatory BP Monitoring. How to interpret?
- Use validated devices
- How to interpret?
=> Mean daytime ambulatory BP >135/85 mmHg is considered elevated.
=> Mean 24 h ambulatory BP >130/80 mmHg is considered elevated.
- A drop in nocturnal BP of <10% is associated with increased risk of CV events.
71
A clinic blood pressure of 140/90 mmHg has a similar risk to what BP for 1) Home pressure average, 2) Daytime average ABP, 3) 24 hours average ABP?
1) Home pressure average
135 / 85
2) Daytime average ABP
135 / 85
3) 24-hour average ABP
130 / 80
72
____% of patients with white coat hypertension diagnosed based on a single ABPM session will have true hypertension on retesting
30-40%
73
Some patients with white coat hypertension develop ____ hypertension
sustained
74
Patients with WCH may be followed with _____ or repeat ABPM could be considered every ___ years
- home BP measurement
| - 1-2 years
75
What is the usual blood pressure threshold values for initiation of pharmacological treatment for
1) Systolic or Diastolic hypertension
2) Diabetes
3) CKD
1) Systolic or Diastolic hypertension
140/90
2) Diabetes
130/80
3) CKD
130/80
76
In low risk patients with stage 1 hypertension (140-159/90-99 mmHg) ____ can be the sole therapy.
lifestyle modification
77
Over __% of Canadians with hypertension have other risk factors and pharmacotherapy should be considered in these patients under what condition?
if BP >/140/90 mmHg with lifestyle modification.
78
When are patients with target organ damage (e.g. left ventricular hypertrophy) are recommended to be treated with pharmacotherapy
if BP >/140/90 mmHg
79
What are the Blood pressure target values for treatment of hypertension
1) Isolated systolic hypertension
2) Systolic/Diastolic Hypertension
3) Diabetes or Chronic Kidney Disease
1) Isolated systolic hypertension
<140
2) Systolic/Diastolic Hypertension
<140, <90
3) Diabetes or Chronic Kidney Disease
< 130, <80
80
What is the goal of therapy? How many drugs does it take to accomplish this usually? Which BP target is it more difficult to achieve? Which BP target is more important to control?
GOAL: To optimally reduce cardiovascular risk, reduce the blood pressure to specified targets.
- The SYSTOLIC target is more difficult to achieve
- However controlling SYSTOLIC BP is as important if not more important than controlling diastolic BP
81
Patients with blood pressure above target are recommended to be followed at least every ____
2nd month
82
What is the purpose of follow up visits?
Follow-up visits are used to increase the intensity of lifestyle and drug therapy, monitor the response to therapy and assess adherence
83
What are the 6 Lifestyle Recommendations for Prevention and Treatment of Hypertension
1. Reduce sodium intake to <2300 mg / day
2. Healthy diet: high in fresh fruits, vegetables, low fat dairy products, dietary and soluble fiber, whole grains and protein from plant sources, low in saturated fat, cholesterol and sodium in accordance with Canada's Guide to Healthy Eating.
3. Regular physical activity: accumulation of 30-60 minutes of moderate intensity cardiorespiratory activity (e.g. a brisk walk). 4-7 days/week in addition to routine activities of daily living
4. Low risk alcohol consumption (≤2 standard drinks/day and less than 14/week for men and less than 9/week for women)
5. Maintenance of ideal body weight (BMI 18.5-24.9 kg/m2).
- Europid, Sub-Saharan African, Middle Eastern: Men = <94cm, Women =<80cm
- South Asian, Chinese: Men = <90cm, Women = <80cm
6. Waist circumference
6. Smoke free environment
84
What are the Dietary Lifestyle Recommendations for Hypertension?
1. High in fresh fruits
2. High in fresh vegetables
3. High in low fat dairy products
4. High in dietary and soluble fibre
5. High in plant protein
6. Low in saturated fat and cholesterol
7. Low in sodium (<2300mg/day)
8. Dietary potassium >80mmol/day
85
What are the potential benefits of a widespread reduction in dietary sodium in Canada? In particular if reduction in average dietary sodium from about 3500 mg to 1700 mg
- 1 million fewer hypertensives
- 5 million fewer physicians visits a year for hypertension
- Health care cost savings of $430 to 540 million per year related to fewer office visits, drugs and laboratory costs for hypertension
- Improvement of the hypertension treatment and control rate
- 13% reduction in CVD
- Total health care cost savings of over $1.3 billion/year
86
What are the Recommendations for daily salt intake?
Less than:
- 2,300 mg sodium (Na)
- 100 mmol sodium (Na)
- 5.8 g of salt (NaCl)
- 1 teaspoon of table salt
- 2,300 mg sodium = 1 level teaspoon of table salt, however, 80% of average sodium intake is in processed foods and only 10% is added at the table or in cooking
87
In hypertensive patients, what reduction in BP was seen when there was 1) an average reduction of 1800 mg sodium/day, 2) an average reduction of 2300 mg sodium/day
Reduction of BP:
1) 5.1 / 2.7 mmHg with a average reduction of 1800 mg sodium/day
2) 7.2/3.8 mmHg with a average reduction of 2300 mg sodium/day
88
In normotensive patients, what reduction in BP was seen when there was 1) an average reduction of 1700 mg sodium/day, 2) an average reduction of 2300 mg sodium/day
Reduction of BP:
1) 2.0 / 1.0 mmHg with a average reduction of sodium 1700 mg/day
2) 3.6/1.7 mmHg with a average reduction of 2300 mg/day sodium
89
Using the FITT principle, what are the Physical Activity Lifestyle Recommendations for Hypertension
1) Frequency
- 4-7 days per week
2) Intensity
- Moderate
3) Time
- 30 - 60 mins
4) Type
- Cardio respiratory activity
- Walking, jogging
- Cycling
- Non-competitive swimming
90
Describe the Weight Loss Lifestyle Recommendations for Hypertensive patients
- Height, weight, and waist circumference (WC) should be measured and BMI calculated for all adults.
- In Hypertensive and all patients with BMI over 25:
1) Encourage weight reduction
2) Healthy BMI: 18.5-24.9 kg/m2
- Waist circumference:
1) Europid, Sub-Saharan African, Middle Eastern: men = >94cm, women = >80cm
2) South Asian, Chinese: men = >90cm, women = >90cm
91
What are the Alcohol Lifestyle Recommendations for Hypertension?
Low-risk alcohol consumption
- 0-2 standard drinks/day
- Men: max of 14 standard drinks/week
- Women: maximum of 9 standard drinks/week
- A standard drink is ~142 ml or 5 oz of wine (12% alcohol). 341 mL or 12 oz of beer (5% alcohol) 43 mL or 1.5 oz of spirits (40% alcohol).
92
What are the Stress Management Lifestyle Recommendations for Hypertension?
Behaviour Modification
- Individualized cognitive behavioural interventions are more likely to be effective when relaxation techniques are employed.
93
Describe the Impact of Lifestyle Therapies on BP in Hypertensive Adults for the following intervention on BP:
1) Reduce food w/added sodium (-1800 mg/day sodium for hypertensive)
2) Weight loss (-1kg)
3) Alcohol intake (-3.6 drinks/day)
4) Aerobic exercise (120-150 min/week)
5) Dietary patterns (DASH diet for hypertensive and normotensive)
1) Reduce food w/added sodium (-1800 mg/day sodium for hypertensive)
=> -5.1/-2.7
2) Weight loss (-1kg)
=> -1.1/-0.9
3) Alcohol intake (-3.6 drinks/day)
=> -3.9/-2.4
4) Aerobic exercise (120-150 min/week)
=> -4.9/-3.7
5) Dietary patterns (DASH diet for hypertensive and normotensive)
=> Hypertensive: -11.4/-5.5
=> Normotensive: -3.6/-1.8
94
Should the extent of blood pressure change from each intervention should be compared? Why or why not?
No because the participants, the type and duration of intervention, and the basic design of the trials differed substantially.
95
Summarize the targets of the following Lifestyle Therapies in Hypertensive adults
1) Reduce foods w/added salt
2) Weight loss
3) Alcohol restriction
4) Physical activity
5) Dietary patterns
6) Smoking cessation
7) Waist circumferene
- Europid
- South Asian, Chinese
Summarize the targets of the following Lifestyle Therapies in Hypertensive adults
1) Reduce foods w/added salt
Target: <2300mg/day
2) Weight loss
Target: BMI <25 kg/m^2
3) Alcohol restriction
Target: 2 drinks/day
4) Physical activity
Target: 30-60 mins 4-7 days/week
5) Dietary patterns
Target: DASH diet
6) Smoking cessation
Target: Smoke free environment
7) Waist circumferene
- Europid: men <94cm, women <80cm
- South Asian, Chinese: men <90cm, women <80cm
96
Draw a diagram showcasing the Epidemiologic impact on mortality of blood pressure reduction in the population
The graph indicates the effect of ‘small’ changes in population BP associated with changes in population changes in lifestyle on the death rates from CVD.
97
What are the 5 Newer modalities of non-invasive used for cardiac imaging?
1) Cardiac positron emission tomography
2) Cardiac magnetic resonance imaging
3) Carotid ultrasound
4) Coronary artery calcium scoring with electron beam or multislice fast CT
5) Coronary artery angiography with multislice fast CT
98
Pros and cons of Cardiac positron emission tomography (3)
1) Is well validated for viability studies
2) Is not useful for detection of atherosclerosis
3) May be useful in the future for detection of inflammation
99
Cons of Cardiac positron emission tomography (2)
1) Current resolution limited by cardiac motion
| 2) Limited role in imaging of atherosclerosis
100
Describe the Carotid Intima Media Thickness (4)
1) Is an Intermediate phenotype for early athero-sclerosis
2) Can be measured relatively simply and noninvasively
3) Can correlate well with histology
4) Increased IMT associated with vascular risk factors and presence of advanced atherosclerosis
101
Describe the methodology to view Carotid Intima Media Thickness
- Longitudinal views of the left and right common carotid artery, carotid bifurcations, internal and external carotid arteries were obtained with ultrasound machine and linear array probe
- Important that linear array probe be at least 7.5 mHz to provide sufficient resolution
- Meyer’s arc device used to record angle of insonation used in obtaining carotid intima-media thickness measurements in longitudinal studies.
102
What are the Pros (4) and Cons (3) of Carotid IMT?
Pros:
1) easy to obtain
2) no radiation exposure
3) well validated
4) useful for intervention studies
Cons:
1) difficult to obtain accurate measurements
2) not useful for individual patient unless it is clearly normal or abnormal
3) debate as to whether IMT or plaque measurements are more useful
103
What is Coronary Artery Calcium Scoring? How can coronary artery calcium be measured?
- Coronary calcium scanning looks for specks of calcium (called calcifications) in the walls of the coronary arteries.
- Calcifications are an early sign of heart disease.
- Coronary artery calcium can be measured with Electron Beam CT scan or multi-detector CT scan.
104
What is Coronary CT Angiography? Previous limitations? How was it overcome? How well does it delineate structures?
- relatively new imaging modality that has been used for non-invasive coronary artery imaging since 2000
- Earlier systems produced images that were of poor quality due to limitations with spatial and temporal resolution and image noise.
- With the introduction of multi-detector computed tomography (MDCT) many problems with image quality have been overcome.
- Coronary CTA clearly delineates the cardiac chambers, the coronary arteries and coronary veins.
105
What are the Pros (2) and Cons (3) of coronary artery CT angiography?
Pros:
1) easy to obtain
2) able to differentiate between soft and calcified plaques
Cons:
1) radiation exposure (dosages varies depending on scanner and protocol)
2) not useful for individual patient follow up
3) current resolution is insufficient to quantify precisely extent of luminal stenosis
106
How is the CV system and renal system inextricably linked?
- kidney one of the major organs involved in whole-body homeostasis which the kidney accomplishes independently but through coordination with other organs, particularly those of the cardiovascular and endocrine system.
- Usually kidney receives ~20-25% of CO; most of this blood flow required to maintain homeostatic or filtration functions of kidney.
- As a result of this close relationship, the two organs must be in constant communication with each other in order to maintain optimal renal and cardiovascular hemodynamics. Achieved through activation of the SNS as well as renin-angiotensin system
107
Describe what happens when blood reaches kidney?
it comes in contact with the basic functional unit of the kidney which is known as the nephron
108
What are nephrons? Fxn?
- Each human kidney contains over one million nephrons.
- Together these nephrons are responsible for performing the FILTRATION FXN of the kidney.
- It is here where the kidney is able to effect its greatest role on the maintenance of whole-body homeostasis.
109
What are the 5 main fxns of the kidneys?
1) maintenance of whole-body homeostasis
2) FILTRATION FXN:
- to regulate the body's acid-base balance, electrolyte concentrations, and control the blood volume
- excrete metabolic wastes e.g. urea, uric acid, creatinine, drugs
3) BP regulation, accomplished via the Renin-Angiotensin-Aldosterone system
4) secretes erythopoietin in response to RENAL HYPOXIA
- erythropoietin has effects on bone marrow, resulting in creation of RBCs
5) central role in vit D synthesis (important in calcium handling)
- direct handling of calcium and phosphorus as well as the activation of vitamin D by hydroxylating 25-hydroxyvitamin D to calcitriol (1,25-dihydroxyvitamin D)
110
What is CKD defined as?
Kidney damage for >/3 months, OR GFR <60 ml/min/1.73 m2 for >/3 months
111
What does kidney lose as a result of CKD?
- represents the loss of the kidneys ability to perform its normal functions
- lose the ability to remove wastes, conserve fluids, and concentrate urine, regulate electrolytes and maintain acid-base balance as well as provide other secondary functions such as anemia management, mineral metabolism, and blood pressure regulation
112
Chronic Kidney Disease is a worldwide public health problem that is estimated to affect around ___% of the population in North America.
10-15%
113
Why is the actual prevalence of CKD is likely under-recognized
the early stages of CKD are often asymptomatic
114
What is the standard method of estimating kidney function
quantification of the glomerular filtration rate (GFR), which is an estimates the volume of fluid filtered from the renal glomerular capillaries into the Bowman's capsule per unit time
115
Why is serum creatinine a less common method of estimating kidney function
not as accurate as GFR in the assessment of kidney dysfunction cause it affected by age, gender, race, body and muscle mass, body fat, metabolic states, pharmacological agents, and laboratory methods
116
What is Stage 1 CKD?
- persons with normal function (eGFR ≥90 ml/min/1.73 m2), but with evidence of kidney damage such as blood or protein in the urine or abnormalities on renal biopsy.
- usually have heritable kidney disorders, such as polycystic kidney disease, where abnormalities in the kidney structure may be found on ancillary testing but the fxn of kidney itself is preserved.
- Usually asymptomatic, with normal BP, and minimal laboratory abnormalities
117
What is Stage 2 CKD?
- patients w/kidney DAMAGE and mild DEC in kidney fxn.
- usually people w/HTN or diabetes with evidence of microvascular dysfunction as manifested by a protein leak in the urine.
- usually asymptomatic however secondary HTN and early abnormalities in mineral metabolism develop during this stage.
- Of note patients with an isolated eGFR of 60-89 without evidence of abnormalities in urine, blood, or imaging are not considered to have CKD
118
What is the criteria for Stages 3-5 CKD?
- based on level of GFR irrespective of the presence or absence of kidney damage.
- GFR < 60 mL/min/1.73 m2 for a period of 3 months are classified as having CKD
- cut-off was chosen due to appearance of multiple metabolic and hormonal abnormalities
119
What is Stage 3 CKD?
- eGFR btwn 30 and 59 ml/min/1.73 m2
- MODERATE degree of renal impairment
- HTN almost universally present
- Symptoms of CKD may or may not be present depending on development of other non-filtration impairments (anemia, bone metabolism etc.)
120
What is Stage 4 CKD?
- eGFR between 15 and 29 ml/min/1.73 m2
- SEVERE loss of kidney function.
- usually affected by typical symptoms of UREMIA such as fatigue, low energy, appetite loss
121
What is Stage 5 CKD?
- (synonymous with end-stage renal disease)
- PROFOUND renal impairment that the kidneys can't fxn at a level that is necessary to sustain day-to-day life
- multiple severe complications and without dialysis or kidney transplantation, DEATH results from accumulation of FLUIDS and WASTES.
122
Draw a diagram showcasing stages 1-5 of CKD and what is the eGFR requirement for each
1) Stage 1: "Damaged"; eGFR >90 mL/min/1.73 m2
2) Stage 2: "Mild"; eGFR 60-89 mL/min/1.73 m2
3) Stage 3: "Moderate"; eGFR 30-59 mL/min/1.73 m2
4) Stage 4: "Severe"; eGFR 15-29mL/min/ 1.73 m2
5) Stage 5: "Profound"; <15mL/min/1.73m2
123
the CKD population is _____-fold more likely to die than to ever progress to the point of requiring renal replacement therapy in the form of dialysis or a kidney transplant
5-100-fold
124
In the CKD population, CVD is ___ as common when compared to the general population and advances at ____ the rate of the underlying CKD
In the CKD population, CVD is TWICE as common when compared to the general population and advances at TWICE the rate of the underlying CKD
125
Why are patients with CKD are much more likely to suffer from atherosclerosis and heart failure, resulting in cardiovascular death, than to eventually require renal replacement therapy.
each 10 mL/min/1.73 m2 decrease in eGFR was associated with a 5% inc in overall CVD, 7% inc in the incidence de novo CVD, and 6% inc in all-cause mortality
126
Now, think whether CKD alters the severity of CVD?
both CKD and CVD were found to be independent risk factors for the primary outcome of a composite of CVD events, stroke, and death. However, individuals with both CVD and CKD were found to be extremely high risk with the presence of both diagnoses conferring an additive risk over and above the presence of each risk factor alone. Likewise, CKD confers an increased risk of adverse outcome after a myocardial infarction. In this study the authors observed 3, 7 and >10-fold increase in mortality with mild (eGFR 51-75 ml/min), moderate (eGFR 35-50 ml/min) and severe)
127
Is CKD an independent risk factor for CVD or is it simply a marker of underlying atherogenic pathology and CVD?
a
128
What can explain the High prevalence of CVD in CKD
- High prevalence of CVD in CKD cause both disorders share common demographic and risk factor profile.
- Risk factors such as hypertension, diabetes, tobacco use, and dyslipidemia result in increased levels of atherosclerosis and CVD. Risk factors also common in the CKD population and inc in prevalence as the disease progresses.
- Dose-response type of effect with increased prevalence of established “traditional” atherosclerotic risk factors, such as diabetes, hypertension, dyslipidemia, and older age as renal function declines.
- hypertension, the second leading cause of CKD, is also a complication of CKD and a major risk factor for accelerated progression of renal disease
- CKD results in salt and fluid retention and thus can worsen pre-existing hypertension and induce and inflammatory response.
- Likewise, CKD is associated with metabolic abnormalities leading to a deranged cholesterol profile.
- CKD itself is responsible for a host of non-traditional risk factors such as Anemia, electrolyte and Mineral metabolism derangements, increased Inflammation, as well as the buildup of Uremic toxins, and Enhanced oxidative stress.
- CKD patients have deficits in measures of cardiopulmonary fitness and strength when compared to normal controls or predicted performance capabilities. These reductions in exercise capacity have been shown to significantly impair quality of life, and to be independently associated with a higher morbidity and mortality
- Several nontraditional factors, such as oxidant stress, and elevated inflammation, are associated with atherosclerosis, with 2 recent reviews suggesting these may be the primary mediators or the “missing link” that explains the tremendous burden of CVD in CKD
- Other factors such as anemia are associated with cardiomyopathy, whereas abnormal calcium and phosphorus metabolism is associated with vascular remodeling and development of noncompliant vessels
129
Describe how the kidney is a central regulator of blood pressure via the renin-angiotensin-aldosterone system.
- If fall in renal perfusion pressure:
1) kidneys release RENIN into the bloodstream which subsequently converts ANGIOTENSINOGEN to ANGIOTENSIN I.
2) ANGIOTENSIN I converted to ANGIOTENSIN II by ANGIOTENSIN CONVERTING ENZYME in the capillaries of the LUNGS.
3) Angiotensin II is also a potent vasoconstrictor which raises BP by increasing vascular resistance.
4) Also, under the influence of Angiotensin II, ALDOSTERONE levels increase. This increases blood sodium levels by decreasing the amount of salt excreted by the kidneys. The retention of salt instead of excreting it into urine increases the blood volume and subsequently blood pressure.
130
How does HTN become more prevalent as renal fxn declines?
HTN induces cardiac abnormalities in the form of LVH induction. In addition, a reduction in coronary reserve and capillary density that occurs in CKD patients exposes them to coronary ischemia, which in turn leads to worsening of ventricular dysfunction.
131
Describe how the kidney induces production of ERYTHROPOIETIN, the endogenous hormone that stimulates production of RBC
kidney cells sense changes in blood oxygenation and signal the renal CORTEX to release ERYTHROPOIETIN. EPO then travels to the bone MARROW where it stimulates the division and differentiation of PROGENITOR cells and induces the release of RETICULOCYTES from the marrow. In the bloodstream, they mature into mature RBCs or erythrocytes
132
How does CKD affect the production of RBC?
- dec RBC production
- reduced lifespan of RBCs
- As eGFR declines below 60 there is a progressive decline in hemoglobin
133
DRAW a diagram demonstrating the effects of low EPO on anemia and peripheral and myocardial tissues
1) Low EPO
- Anemia
- Direct effects via EPO-R
2) Anemia
- Reduced myocardial oxygenation
- Inc CO and reduced systemic vascular resistance
- Oxidative stress
- SNS activation
3) Direct effects via EPO-R
- myocyte necrosis and apoptosis
4) Reduced myocardial oxygenation
- myocyte necrosis and apoptosis
5) Myocyte necrosis and apoptosis
- LV Hypertrophy and then LV dilatation and heart failure
6) Inc CO and reduced systemic vascular resistance
- LV Hypertrophy and then LV dilatation and heart failure
7) Oxidative stress
- LV Hypertrophy and then LV dilatation and heart failure
8) SNS activation
- LV Hypertrophy and then LV dilatation and heart failure
134
DESCRIBE the effects of low EPO on anemia and peripheral and myocardial tissues
- Low EPO leads to anemia
- Low EPO also has direct effects on peripheral and myocardial tissues
- Low EPO leads to inability to protect cardiac muscle cells from necrosis and programmed cell death or apoptosis
- Anemia results in a multitude of cardiovascular derangements including Reduced myocardial oxygenation, increased CO and reduced systemic vascular resistance, SNS activation and Oxidative stress
- The end result is LV Hypertrophy followed by LV dilatation and heart failure
135
What pharmaceuticals are available for CKD-anemia
Recombinant human erythropoietin and other erythropoiesis stimulating agents (ESA)
136
Describe the steps in the formation of vitamin D to its function
1) Vitamin D3 synthesized from cholesterol
2) Then photolyzed by UV light to pre-vitamin D3.
3) Pre-vitamin D3 then hydroxylated in the liver to 25-hydroxycholecalciferol
4) Then further hydroxylated in the kidneys by the enzyme 1α-hydroxylase, into 1,25-dihydroxycholecalciferol.
5) Then calcitriol released into the circulation, where it is transported to various target organs and binds the vitamin D receptor.
6) Vitamin D receptors are expressed by cells in most organs, including the brain, heart and skin.
7) Through receptors, vitamin D has its biologic effects on calcium and phosphate levels by promoting their absorption from food in the intestines, and by promoting re-absorption of calcium in the kidneys.
137
How do the kidneys play a vital role in the regulation of mineral metabolism
through the direct handling of calcium and phosphorus as well as the activation of vitamin D by hydroxylating 25-hydroxyvitamin D to calcitriol (1,25-dihydroxyvitamin D)
138
How does the phosphorus and calcium levels change during earl CKD?
- phosphorus levels INC due to reduction in renal clearance
- calcium levels DEC due to DEC calcitriol synthesis with resultant decreased calcium absorption from the gut and decreased calcium release from bone
139
Draw a diagram describing the production of Vitamin D
1) Vitamin D ---(Liver)--> 25-OH Vitamin D3 ---(Kidney)--> 1,25-OH Vitamin D3
2) 1,25-OH Vitamin D3 --> Kidneys
3) Kidneys --> (Calcium absorption) and (Dec phosphate reabsorption)
4) 1,25-OH Vitamin D3 --> Bone
5) Bone -> Calcium release
6) 1,25-OH Vitamin D3 --> Intestines
7) Intestines -> (Calcium absorption) and (Phosphate absorption)
140
What medical problems is Vit D deficiency associated with?
1) Bone disease (Rickets, Osteoporosis, renal...)
2) Multiple Sclerosis
3) Parkinson’s
4) Cancer
5) Inc levels of inflammation
6) abnormalities in insulin handling with resultant metabolic syndrome or overt diabetes
7) abnormalities in the renin-angiotensin-aldosterone axis leading to HTN andLVH
8) All of the above act to worsen atherosclerosis, leading to an end result of increased adverse cardiovascular outcomes.
141
Draw a diagram showing effects of Vit D deficiency
1) Vit D deficiency -->
- Insulin resistance
- Elevated PTH
- Inc RAAS
2) Elevated PTH -->
- Insulin resistance
- Inflammation
- Inc RAAS
3) Insulin resistance -> Diabetes and Metabolic Syndrome
4) Inc RAAS -> HTN and LVH
5) Inflammation -> Atherosclerosis
6) Diabetes and Metabolic Syndrome -> Atherosclerosis
7) HTN and LVH -> Atherosclerosis
8) Atherosclerosis -> Adverse CV events
142
How does renal decline in the CKD population lead to malignant calcification?
Renal decline leads to a precarious balancing act:
- On one hand, causes vit D deficiency and the resultant ill-effects and hypocalcemia
- On other hand, upregulation of PTH and well as a reduction in the ability of the kidney to eliminate phosphates
- This combination predisposes patients to malignant calcification
- Excess calcium can be deposited into soft tissue but also into blood vessels, myocardium, and cardiac valves. Accelerated calcifying atherosclerosis of the coronary, aortic, and iliofemoral circulations as well as valvular heart disease occur with high frequency in CKD and especially dialysis patents.
143
Where can calcium be deposited in the arteries?
- either the intimal or medial layers w/fundamentally different consequences
- Both intimal and medial calcification are generally co-localized to the coronary, aortic, and ilio-femoral vessels.
144
Describe the medial layer of arteries and how medial layer calcification changes this?
- media mainly consists of elastic tissues and smooth muscle that gives arteries their elastic properties
- Medial layer calcification is associated with stiffening of the vasculature and reduced compliance
- This in turn worsens blood pressure resulting in a rise in systolic blood pressure, an unchanged diastolic pressure, a widened pulse pressure, and an increase in pulse wave velocity
- These changes, in turn, result significant adverse cardiovascular outcomes including LVH, which results in increased CV risk.
145
Describe the intima layer of arteries and how intimal layer calcification changes this?
- innermost later is the intima; consists mainly of endothelial cells which contact BF
- Intimal deposition of calcium relatively less common but mainly associated with atherosclerotic plaques
- As intimal lesions narrow the arterial lumen the BF may be compromised leading to distal ischemia
- As well, acute ischemic events, such as myocardial infarction, may result when these plaques rupture and thrombosis occludes the vessel lumen.
146
It is postulated that this calcification is multifactorial and is related to:
I thought calcification wad due to Vit D defiency??
1. Iatrogenic Vitamin D therapy and calcium-phosphate binders (therapies used to combat the mineral metabolism abnormalities of CKD).
2. As a function of age and Time on Dialysis
3. Serum Phosphate level. Patients with ESRD have severe changes their Calcium and Phosphate levels, which, at critical point, induces trend toward ectopic calcification. # of ectopic calcification sites related to serum phosphate level. 10-27% greater risk of all-cause and cardiovascular mortality with increasing phosphate levels.
4. Related to intrinsic inhibitors of calcification. For example, subjects with CKD and low levels of Fetuin A, an inhibitor of calcification produced in the liver, are associated with enhanced vascular calcification and increased CV mortality. Likewise, osteoprotegrin regulates bone breakdown by controlling the bone degredation cells known as osteoclasts. In patients with CKD elevated Osteoprotegerin levels correlate with vascular calcification, and predict mortality in hemodialysis patients. These effects seem to be magnified in individuals with high C-reactive protein levels.
147
It is known that between ____% of CKD patients have elevated serum levels of inflammatory markers such as C-reactive protein, fibrinogen, interleukin-6 among others.
30-50%
148
What are the 4 reasons as to why CKD, and especially ESRD, is a pro-inflammatory state?
due to a multitude of pathophysiologic changes:
1) In CKD, due to decreased renal clearance, there's accumulation of pro-inflammatory cytokines. E.g. serum half-lives of TNF-a and IL-1, are greater in patients with CKD than those with normal renal function. Likewise, levels of IL-6, CRP and hyaluronan are inversely related to eGFR.
2) The chronic volume overload associated with CKD leads to altered GI permeability which leads to the accumulation of endotoxins and bacteria which further stimulates pro-inflammatory cytokine release.
3) Accumulation of excess free-radicals in CKD with a concurrent loss of anti-oxidants. This combo further enhances pro-inflammatory cytokine release.
4) Frequent occurrence of comorbid illnesses in renal patients enhances the hyper catabolic state and the development of inflammation
149
What Can We Do About CVD in Patients with CKD?
TARGETING CKD:
1) recognize CKD early in it’s course and prevent it’s progression (regular screening with eGFR measurements and urine albumin:Cr)
2) aggressively treat the derangements associated with CKD. E.g. erythropoiesis stimulating agents (i.e. erythropoietin)
- ESAs result in a decrease in left ventricular mass as well as a survival benefit after the initiation of dialysis
3) derangements of mineral metabolism should be corrected aggressively with dietary modification and Phosphate Binders such as calcium carbonate, sevalamer to minimize the aforementioned ill-effects
TARGETING CVD:
4) pursue aggressive CV risk stratefication and risk Factor modification
5) Hypertension should be aggressively managed to a target blood pressure of less than 130/80 e.g. diuretics and blockers of the renin aldosterone system such as ACE Inhibitors, and Angiotensin-Receptor blockers are preferred
6) lifestyle measures are first line for abnormalities of triglycerides and HDL however pharmacotherapy with a fibrate or statin may be required
7) smokers should be counseled with regards to the benefit of smoking cessation
8) combination of flexibility, strengthening and aerobic exercise training, renal rehabilitation programs have been shown to exert beneficial effects on physical fitness (aerobic and resistance), psychosocial function, quality of life (sickness impact and symptom scores), cardiorespiratory parameters (including LV systolic function) and renal functional parameters in patients with moderate-severe CKD
