Nutrition Exam 2-Cvd

Front 1

What is Coronary Heart Disease Rates?

Back 1

• Coronary heart disease is the most common form of cardiovascular disease and causes nearly half of all deaths in the US
• Mortality rates from CHD have been rising for many years and seem to be leveling off now. The high sustained level of mortality rates is ultimately caused by a combination of dietary and other lifestyle factors
• Successful prevention and treatment depends on understanding the disease mechanisms and applying appropriate interventions]

Front 2

• What is Atherosclerosis Progression?

Back 2

o Unaffected artery: thin intimal layer, smooth luminal surface
o Early lesions: tears or fatty streaks (one of the earliest lesions in the progressive development of atherosclerosis; foam cells are a predominant feature of these lesions) in the intima attract monocytes and stimulate cellular immune response
o Advanced lesions: cholesterol, calcium crystals and cellular debris accumulate within the intima which starts bulging into the arterial lumen
o Thrombus formation: clotting factors and platelets are activated by contact with lesions, thrombus may build on lesion or move downstream, blocking the artery
• Usually develops imperceptibly in young adulthood and do not have symptoms until many years later
• Many factors promote progression, some act by promoting early lesions, others by promoting late events (calcification and thrombus formation) specific dietary factors influence progression at all stages

Front 3

• Diet and atherosclerosis

Back 3

o Stages 2 and 3 (early and advanced lesions): obesity and high intake of saturated fat and cholesterol are unfavorable; adequate intake of fiber, folate, antioxidants, and vitamin K is protective. Intake patterns that decrease blood pressure (moderate sodium chloride, adequate potassium, calcium and magnesium) slow progression.
o Stage 4 (thrombus formation): regular consumption of fish may be protective

Front 4

• Several mechanisms promote atherosclerosis

Back 4

o Atherogenic (promotes the development of atherosclerosis, or lipid accumulation and other changes in the lining of the arteries) actions of LDL and other lipoproteins
o Atherogenic actions of homocysteine (end product of methionine metabolism; toxic to the vascular endothelium)
o Vascular damage due to hypertension
o Hardening of the arteries with diabetes or vitamin K inadequacy

Front 5

• Some factors promote thrombus formation

Back 5

o Increased platelet aggregation due to low fish and low fruit/vegetable intake
o Hypercoagulation with high fat intake and obesity

Front 6

• What Fatty acids required for the functions of the body

Back 6

• Most of the fatty acids in the body come from dietary fat (not from carbohydrate, protein or alcohol) and are used:
o To build membranes (cholesterol and phospholipids)
o As a precursor for complex lipids
o As a precursor for eicosanoids (compounds derived from 20-C polyunsaturated fatty acids (omega-3 and omega-6); the protaglandins, thromboxanes, and leukotrienes are all eicosanoid derivatives and are important in the inflammatory response and platelet aggregation
o To provide for current and future energy needs
o Example: the myelin sheath on neural axons contains essential fatty acids which must be supplied by the diet
• Lipids must be transported as lipoproteins because they are not miscible with water, if they weren’t they would clog blood vessels

Front 7

• Lipoproteins: Structure

Back 7

o Triglycerides and other complex lipids in blood are transported as lipoproteins. There are several types of lipoproteins, but they all contain the following in varying amounts: cholesterol, cholesterol esters, triglycerides, phospholipids, and apolipoproteins

Front 8

• Atherogenic vs. nonatherogenic lipoproteins

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o The following lipoproteins are usually present during some part of the day in the blood of all healthy people:
 Atherogenic lipoproteins:
• Chylomicron remnants (the remaining particles of chylomicron and VLDL after much of the triglyceride has been cleaved off by lipoprotein lipase)
• LDL (a transporter of fat and cholesterol; high LDL levels are associated with CVD)
 Nonatherogenic lipoproteins
• Chylomicrons (a lipoprotein complex formed in the intestinal mucosa during the absorption of fat for the purpose of transport; joins the lymphatic circulation to enter the blood via the thoracic ducts)
• HDL (involved in VLDL and chylomicron metabolism and function in reverse cholesterol transport for excretion in the bile)
• VLDL (a transporter of fat and cholesterol that is produced in the liver; VLDL remnants are associated with the development of atherogenesis)

Front 9

• Post-absorptive transport of lipids

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o Chylomicrons are lipoproteins that function to transport fat-soluble compounds form the intestine to other organs
o Chylomicrons carry:
 Triglycerides (for fuel and to supply essential fatty acids)
 Cholesterol (for membrane, steroid hormone and bile acid synthesis)
 Vitamin A and beta-carotene (for vision pigments, growth modulation)
 Vitamin D (for calcium metabolism, growth modulation)
 Vitamin E (antioxidant)
 Vitamin K (blood coagulation, calcium metabolism)
o Clinical Information: People who cannot produce chylomicrons due to genetic defects usually suffer from severe neural degeneration (neuropathy). The reason is that the lack of chylomicrons interrupts the transfer of vitamin E (alpha-tocopherol) from the intestines to neurons and other target tissues. This block can be overcome by vitamin E injections or by oral doses that are 1000x higher than normal.

Front 10

• Route of chylomicrons

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o Mouth to stomach: a meal containing fat is ingested and enters the GI tract
o Small intestine Step 1: dietary fat is cleaved by pancreatic lipase in the small intestine
o Small intestine Step 2: mixed micelles made of fatty acids, monoglycerides, bile acids and phospholipids are absorbed in the small intestine
o Small intestine Step 3: simultaneously, chylomicrons carrying dietary fat enter intestinal lymph ducts and are transported through the thoracic duct into the circulation
o Lungs: the lungs receive the first release of fatty acids; essential fatty acids are needed for surfactant production
o Muscles: fatty acids are a very energy-dense fuel; they are metabolized in the muscles through beta-oxidation and acetyl-CoA enters the TCA cycle
o Adipose tissue: stores fatty acids that are not taken up by muscle and other tissues
o Hepatic artery: most chylomicrons reach the hepatic artery only after many passes through the circulatory system
o Liver: chylomicrons that have become small remnants bind to apoE receptors and are taken up into hepatocytes

Front 11

• Chylomicron clearance proceeds in 2 steps

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o Hydrolysis of triglycerides by lipoprotein lipase (activated by apolipoprotein CII) in the bloodstream (in small arterioles and capillaries)
o Receptor mediated uptake of the residual lipoproteins (chylomicron remnants)
• Normally chylomicrons are cleared from the bloodstream within a few hours and their lipids are taken up by muscle, adipose, liver, bone marrow and other tissues

Front 12

• Triglyceride levels and diet

Back 12

o Genetic disposition and dietary habits jointly determine the postprandial (following ingestion of a food or meal) chylomicron remnant concentration in blood. People eating large meals with lots of fat tend to have more of these potentially atherogenic lipoproteins.
o Elevation of serum triglycerides is recognized as an independent risk factor for coronary heart disease. High triglyceride levels (200-449 mg/dl) and very high triglyceride levels (above 500 mg/dl) can be caused by obesity, lack of physical activity, or high carbohydrate diet. Elevated triglycerides are often seen in those with metabolic syndrome (a collection of risk factors: insulin resistance, hypertension, abdominal obesity, low HDL and elevated triglycerides) or with diabetes
o Clinical Information: In normal persons, the amount of fat eaten with a typical American meal saturates remnant clearance pathways. This prolongs circulation of these potentially atherogenic lipoproteins. Eating less fat at each meal reduces the exposure of the vascular endothelium to chylomicron remnants

Front 13

• Lipid transport from the liver

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o VLDLs are lipoproteins that function to transport lipids from the liver to muscle and other organs.
o VLDL transport:
 Triglycerides (for fuel and to supply essential fatty acids)
 Cholesterol (for membrane and steroid hormone synthesis)
 Vitamin E (antioxidants)

Front 14

• Catabolism of VLDL proceeds in two steps

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o Lipoprotein lipase (LPL) cleaves triglycerides to be taken up by muscle, adipose and other tissues, generating VLDL remnants
o About half of the VLDL remnants are taken up in a receptor-mediated process. The other half are converted to LDL in the liver
• VLDL are in many ways similar to chylomicrons, the intestinal triglyceride-rich lipoprotein. They are both catabolized by LPL. However, hydrolysis of triglyceride in VLDL is much slower than that of triglycerides in chylomicrons

Front 15

• Comparison of VLDL and chylomicron metabolism

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o Synopsis of human chylomicron and VLL metabolism
 Chylomicrons: produced in the small intestinal mucosa, half life of minutes, none is converted to LDL
 VLDL: produced in the liver, half life of hours, more than 50% is converted to LDL
o Remnant clearance (refers to the time it takes for the uptake of chylomicron and VLDL particles that have a large proportion of their triglycerides released) is easily saturable. When a lot of remnants compete for clearance, a larger proportion of VLDL remnants are converted into LDL. This often happens with a high-fat diet (more than 30% total energy from fat.)

Front 16

lipid metabolism and liver function

Back 16

• Human lipoprotein metabolism differs in important ways from that of commonly used laboratory rodents. In particular, the interpretation of diet effects in animal experiments needs to take these species differences into account.
• Clinical information: When liver function is impaired, the liver may not be able to export excess triglyceride with VLDL, and triglyceride deposits can accumulate to pathological levels within days. The impairment of lipid export with VLDL contributes to the development of fatty liver in people with chronic alcohol abuse.

Front 17

• LDL: cholesterol rich lipoproteins

Back 17

o LDLs are derived from VLDLs. They are very cholesterol-rich and promote atherosclerosis
o LDL carry:
 Cholesterol
 Vitamin E

Front 18

• LDL clearance in high vs. low cholesterol diet

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o The liver takes up LDL from the blood through LDL receptors and other receptors. LDL clearance from the blood takes many days, depending on receptor activity. Cellular LDL cholesterol uptake is regulated to ensure and adequate supply of cholesterol for the synthesis of membranes, hormones, and other critical compounds. The liver converts some cholesterol into bile acids while some is directly secreted into bile. People eating cholesterol-rich foods take up more cholesterol in the liver. Fewer LDL receptors are synthesized when cells have enough cholesterol; therefore fewer receptors are expressed due to increased intracellular cholesterol. As a result of LDL receptor down-regulation, LDL uptake is slowed.
o Dietary cholesterol intake influences LDL receptor activity in liver:
 High cholesterol diet: only a few LDL receptors are expressed in liver cells; net effect: serum LDL concentration is higher due to delayed clearance
o Cholesterol is an essential substance for all cells for building membranes and synthesizing many vital molecules. The adrenal glands contain the cells with the highest LDL receptor activity; these adrenal cells use cholesterol for steroid hormone synthesis.

Front 19

• Cholesterol excretion into bile

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o LDL, just like HDL, can move cholesterol from arteries and other peripheral tissues to the liver. The liver can then excrete cholesterol either directly or after conversion into bile acids.
o High cholesterol intake slows receptor-mediated LDL uptake into the liver and makes it harder to remove excess cholesterol from the body.

Front 20

• Dietary fatty acids and blood cholesterol

Back 20

o Some fatty acids lower LDL; others raise it.
Fatty Acid Found in
Strongly cholesterol raising
• 14:0 myristic acid
• 16:0 plamitic acid
• Trans-fatty acids
Butter, milk fat, meats, coconut
Shortening
Partially hydrogenated oils
Neutral or mildly cholesterol raising
• 18:0 stearic acid
• 18:1 oleic acid
• 16:1 palmitoleic acid
Beef fat, chocolate
Olive oil, canola oil, almonds
Palm oil
Cholesterol lowering
• 18:2 linoleic acid
• 18:3 alpha-linolenic acid
• 20:5 eicosapentaenoic acid (EPA)
• 22:6 docosahexanoic acid (DHA)
Seeds and vegetable oils, walnuts
Flaxseed (linseed)
Salmon, trout, herring, mackerel
Salmon, trout, herring, mackerel

Front 21

• Substituting types of fat

Back 21

o What would be the effect on serum cholesterol concentration if half the fat in a typical US diet were replaced with a different type of fat?
 Typical US diet: total serum cholesterol = 260, least amount of polyunsaturated fatty acids, approximately 1/3 monounsaturated fatty acids, more saturated fatty acids and a small amount of trans-fatty acids
 Vegetable shortening: total serum cholesterol = 275, least amount of polyunsaturated fatty acids  saturated fatty acids  monounsaturated fatty acids  trans-fatty acids
 Stick margarine: total serum cholesterol = 227, saturated fatty acids  trans-fatty acids  polyunsaturated fatty acids  monounsaturated fatty acids
 Olive oil: total serum cholesterol = 207, polyunsaturated fatty acids  saturated fatty acids  monounsaturated fatty acids
 Soybean oil: total serum cholesterol = 176, saturated fatty acids  monounsaturated fatty acids  polyunsaturated fatty acids
 Safflower oil: total serum cholesterol = 154, saturated fatty acids  monounsaturated fatty acids  polyunsaturated fatty acids

Front 22

• LDL concentration modifiers

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o Factors influencing serum LDL concentration:
 Genetics
 Body weight and exercise
 LDL-raising dietary factors: saturated and trans-fatty acids, cholesterol
 LDL-lowering dietary factors: polyunsaturated fatty acids, viscous dietary fiber (pectin and beta-glucan) in oats, barley, legumes and fruits, soy protein, plant stanols/sterols in nuts, seeds, vegetable oils added to margarines and other foods, antioxidants, flavonoids in fruits, vegetables, wine, and tea
o The bottom line: lifestyle changes can reduce excessive LDL concentrations by 20-40%
o Clinical Information: Dietary cholesterol increases blood LDL noticeable in a few people; in others the effect is much smaller. A common variant of apolipoprotein E (E4), present in about 25% of all people, is one of the genetic factors increasing responsiveness to dietary cholesterol.

Front 23

• Effective ways to lower LDL

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o Lower total fat intake
o Reduce excess body fat
o Replace some of the SFA with PUFA
o Eat some cold water fish (with omega-3 fatty acids)
o Avoid trans-fatty acids
o Reduce cholesterol intake
o Increase dietary fiber intake

Front 24

• Polyunsaturated fatty acids and free radicals

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o PUFAs are susceptible to peroxidation. Oxidized lipids are more atherogenic than their native forms. Among lipoproteins, LDL are most susceptible to peroxidation due to their high PUFA content and long half-life in circulation.
o Steps:
 Initial free radical attack
 Forms a lipid radical
 Then a peroxy radical
 Free electron attacks
 Another fatty and another…

Front 25

• Oxidized LDL

Back 25

o When free radicals attack LDL, its protein moiety, apoB, may be fragmented or otherwise modified and the unsaturated fatty acids become oxidized. In this state, modified LDL is no longer recognized by its normal receptor, but can bind to one of several alternative receptors. Most important for the binding of modified LDL is the scavenger receptor, which allows its uptake by macrophages and other extrahepatic cells and promotes the progression of atherogenesis.
o Clinical Information: The generation of some of the most toxic free radicals is catalyzed by free iron and copper. This may explain the suggestion from some studies that people with excessive iron stores have an increased cardiovascular and cancer risk.

Front 26

• LDL Uptake by macrophages

Back 26

o Prolonged circulation of LDL allows more time for oxidation. With high LDL levels in blood, more LDL enters endothelium of the arteries. LDL is further oxidized in the endothelium, stimulating uptake by macrophages. Macrophages with an excess cholesterol load turn into foam cells and die. Dead and dying foam cells deposit their cholesterol in the vascular endothelium. Fatty streaks and advanced atherosclerotic lesion contain many foam cells and accumulated cholesterol. Modified LDL and oxidized lipids stimulate secretion of mediators by endothelial cells. This promotes smooth muscle cell proliferation, attracts macrophages, and increases inflammatory response.

Front 27

• Free radical defense mechanism

Back 27

o Defense mechanisms against oxygen free radicals
 Protective cellular enzymes inactivate free radicals as these are generated (superoxide dismutase, catalase)
 Fat-soluble antioxidants protect membranes, lipid-rich organelles and lipoproteins (alpha-tocopherol content of LDL, carotenoids)
 Proteins and metabolites protect aqueous environments within and outside cells (albumin, uric acid, ascorbic acid)
o The different antioxidants are interdependent and have complementary free-radical scavenging activity. This may explain why fruits and vegetables have been shown to reduce the risk of free radical-related chronic disease, while supplements seem to be less effective.
o One example: ascorbic acid is required to regenerate alpha-tocopherol after it has scavenged a free radical. Without this regeneration, alpha-tocopherol itself becomes a pro-oxidant.

Front 28

• NO signal disruption

Back 28

o Free radicals and oxidized lipids and lipoproteins (OX-LDL) may interfere with NO signaling in vascular smooth muscle cells. Normally NO promotes the relation of smooth muscle cells which reduces arterial resistance, thereby decreasing cardiac load. Interference with this signaling system can increase arterial resistance.

Front 29

• Steps in cholesterol synthesis

Back 29

o Acetyl- CoA
o Acetoacetyl-CoA
o HMG-CoA
o Mevalonate
o Isopentenyl PP
o Geranyl PP
o Farnesyl PP
o Squalene
o Lanosterol
o Desmosterol
• The rate limiting step in cholesterol synthesis is the conversion from HMG-CoA to mevalonate. Without this substrate, cholesterol synthesis cannot proceed. The enzyme that catalyzes this reaction is HMG-CoA reductase. Its activity decreases when there is adequate or excess cholesterol from the diet.

Front 30

HDL

Back 30

• HDLs are relatively small and dense, and contain more proteins and phospholipids than other lipoproteins. The HDL contain enzymes and proteins such as LCAT and apolipoprotein E (apoE)

Front 31

• The main functions of HDL are:

Back 31

o To transfer apoCII and apoE to chylomicrons and VLDL to regulate their metabolism
o To take up cholesterol and phospholipids from VLDL
o To take up cholesterol from LDL
o To remove cholesterol from peripheral tissues (reverse transport)
• Low values of HDL are associated with increased cardiovascular risk. Guidelines in The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) suggest keeping HDL above 40 mg/dl.

Front 32

• Reverse cholesterol transport

Back 32

o HDL, in addition to LDL, transports potentially damaging cholesterol from arteries to the liver. This reverse cholesterol transport is important, because only the liver can excrete significant amounts of cholesterol (via the bile duct).
o The liver is the central organ for cholesterol excretion. Hepatocytes have several types of receptors which mediate lipoprotein uptake. Some of the lipoprotein cholesterol is converted into bile acids. Both bile acids and cholesterol can then be secreted into bile.

Front 33

• Factors influencing HDL levels

Back 33

o Both constitutional and lifestyle factors jointly determine HDL concentration
o Constitutional factors
 Gender: women have about 20% higher HDL than men
 Various genetic factors
 Hormonal status (HDL levels decrease after menopause)
o Lifestyle factors
 Activity level (high level increases HDL)
 Excess weight (decreases HDL)
 Alcohol consumption (increases HDL)
o People with moderate alcohol use (not more than one drink per day for women and two drinks per day for men) have lower cardiovascular risk than both non-drinkers and more excessive drinkers. One drink is defined as 5oz wine, 12oz beer, or 1.5 liquor.

Front 34

How is it possible that the French eat so much fatty meat and dairy and still have less cardiovascular disease than the other Europeans or the American population?

Back 34

Some researchers have suggested that the atherogenic effect of food is partially offset by their high wine consumption. However, the validity of this explanation is still under dispute. Note: There have been reports that nonalcoholic extracts of red grape skins also raise HDL concentrations. The active principle is thought to be polyphenols.

Front 35

• Typical diets in different cultures

Back 35

o US: fast food, high saturated fat, moderate polyunsaturated fat, 120g total fat, low fiber intake, low intake of many B vitamins, ratio of polyunsaturated to saturated fat = 0.4 (close to 1.0 is desireable), LDL cholesterol = 150 mg/dl
o Japan: very low fat food, low saturated fat, moderate polyunsaturated fat, 40g total fat, P/S ratio = 1.0, LDL cholesterol = 90 mg/dl
o Mediterranean: vegetables, olive oil, low saturated fat, moderate polyunsaturated fat, high monounsaturated fat, 90g total fat, P/S ratio = 1.0, LDL cholesterol = 100 mg/dl

Front 36

• Heart Healthy Recommendations

Back 36

o Maintain a healthy body weight: match energy intake to energy needs if weight maintenance is desired; expenditure should exceed intake if weight loss is needed. Emphasize nutrient-dense foods while limiting those that are high in caloric density
o Saturated and trans-fat intake should be 8% or less of calories: substitute vegetables, leguemes, nuts, and fish for animal foods. Limit the amount of prepared foods containing partially hydrogenated vegetable oil (cookies, crackers, baked good, fried foods, margarines). Select fat-free or low-fat dairy
o Cholesterol intake less than 300 mg/day: substitute vegetables, legumes, nuts, and soy products for animal foods. Choose fat-free or low-fat dairy
o At least 2 servings of fish/week: choose fish that are rich in omega-3 fatty acids such as salmon, trout, and herring
o Clinical Information: Due to the risks of mercury intoxication, pregnant and lactating women as well as young children should be careful with the type and amount of fish they consume weekly. Currently the FDA advises women who are pregnant or nursing, or might become pregnant, and young children to avoid fish with high mercury levels (1ppm) including shark, swordfish, mackerel, and tilefish. Other fish with lower mercury levels (0.5ppm) can be consumed up to 12oz/week (2 average meals). White albacore tuna has more mercury than canned light tuna, so it should be limited to 6oz per week as one of the average meals. Recreationally caught fish should be checked with local advisories for safety. Women not of childbearing age and men can consume up to 7oz of fish with high mercury levels/week and up to 14oz of fish with lower mercury levels.
o Emphasize fruits and vegetables: aim for at least 4 servings of fruits, and 4 servings of vegetables each day
o Include whole grains and high-fiber foods: choose at least 6 servings of a variety of grain products each day
o Limit salt intake to less than 6g/day or 2300mg: prepare more foods using fresh ingredients; read food labels to choose processed food with less sodium
o Limit alcohol to 2 drinks/day for men, 1 drink/day for women
o Limit intake of foods and beverages with added sugar: choose water and unsweetened beverages frequently. Read food labels to choose foods lowest in added sugar.
o Clinical Information: Myristic and plamitic acid are the fatty acids with the greatest cholesterol-raising potential. Food with a high proportion of myristic and palmitic acid are butter, whole mik, cream, and high-fat cheeses.

Front 37

• Blood pressure regulation

Back 37

o Overall regulation of blood pressure is achieved through the rennin-angiotensin system, which resides in the kidney. Additional mechanisms exist that control blood pressure at local sites.

Front 38

• Renin

Back 38

o Renin is an enzyme that catalyzes the first in a series of steps that ultimately results in the release of the hormone aldosterone. The main role of aldosterone is to maintain blood pressure by conserving sodium.
o Renin will be released from the kidney in response to:
 Decreased arterial pressure
 Decreased plasma volume
 Low plasma sodium
 Edema
 Activation of the renal nerve

Front 39

• Angiotensin

Back 39

o Angiotensinogen  (via Renin – kidney) Angiotensin I  (via enzyme of pulmonary origin) Angiotensin II
o Angiotensin II does the following
 Vasoconstriction (increases blood pressure)
 Brain to stimulate thirst and secrete ADH
 Acts on proximal tubules of the kidneys to conserve sodium (increases blood pressure)
 Stimulates adrenals to form aldosterone (increases blood pressure)

Front 40

• Aldosterone

Back 40

o Acts on the renal tubules in the kidney to increase sodium reabsorption. This helps to restore extracellular volume as water accompanies the reabsorption of sodium
o Acts on ascending tubule

Front 41

• Factors influencing vascular resistance

Back 41

o Blood pressure refers to the mean arterial pressure and is basically the result of two components: cardiac output and systemic vascular resistance
Factor Example Effect on Blood Pressure
Circulating hormones Norepinephrine Increases
Neurotransmitters Norepinephrine Increases
Local paracrine and autocrine systems Nitric oxide Decreases
Structural vessel changes Loss of elasticity with age increases

Front 42

• At risk populations: people with the following traits have an increased risk for developing hypertension

Back 42

o Obesity
o Diabetes
o Advanced age (over 65 years)
o Low socioeconomic status
o Sedentary lifestyle
o Ethnicity: African Americans, Hispanics
o Alcohol abuse
o Family history
• Genetic and environmental factors contribute jointly to the development of hypertension
• Clinical Information: 65 million Americans (1 in 3) have elevated blood pressure or are taking antihypertensive medication as estimated by the NHANES IV study.

Front 43

• Hypertension as a CVD risk factor

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o Hypertension is an independent risk factor for cardiovascular disease
o Hypertension, diabetes, and obesity often occur together
o Heart attacks and strokes occur 2-3 times more often in people with untreated hypertension
o Compared with a blood pressure of 115/75, the risk of CVD doubles for each increment of 20/10. Diet modification usually can lower blood pressure by more than 20/10.
• Clinical Information: “The relationship between BP and risk of CVD events is continuous, consistent, and independent of other risk factors. The higher the blood pressure, the greater the chance of heart attack, heart failure, stroke, and kidney disease”

Front 44

• Metabolic syndrome

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o Many people with hypertension have a cluster or risk factors known as metabolic syndrome (sometimes referred to as syndrome X) which is strongly associated with type 2 diabetes. People with metabolic syndrome are at particularly high risk for CVD and events.
o Three of the five must be met for metabolic syndrome to be diagnosed
 Elevated waist circumference
 High triglyceride levels
 Low HDL levels
 High blood pressure
 Elevated fasting glucose
o The underlying factors are obesity, insulin resistance, and sedentary lifestyle.
o In cardiology, Syndrome X is a problem with heart rate regulation

Front 45

• Role of minerals in hypertension

Back 45

o Sodium is one of several minerals (sodium, calcium, potassium, and magnesium) that play a role in hypertension

Front 46

• Sodium intake and hypertension

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o Over the last few decades, epidemiological, experimental, clinical, and genetic analyses have shown strong evidence that high sodium intake elevates blood pressure and that hypertension can be managed by maintaining low sodium intake.

Front 47

• Salt-sensitivity

Back 47

o Blood pressure in many people will vary in response to dietary salt intake. These individuals are identified as being “salt-sensitive”.
o Salt-sensitive individuals have an increased arterial pressure with increased dietary salt intake – although the mechanism of action for this response is not clear
o It is estimated that 50-60% of individuals with hypertension are salt-sensitive
o Clinical information: Hypertension is usually defined as systolic blood pressure of 140 mm Hg or greater and/or diastolic blood pressure of 90 mm Hg or higher averaged over two or more separate office visits

Front 48

• Effect of sodium chloride

Back 48

o Factors that influence the effect of sodium chloride restriction on blood pressure levels include
 Age (elderly are more responsive)
 Race (African Americans are more responsive)
 Blood pressure level (higher levels are usually more responsive)
 Genetic variation
 Renal abnormalities
 Obesity
 Abnormal renin-angiotensin system
 Low renin levels/slow renin response
o Most people with hypertension benefit from maintaining a low sodium diet; some will benefit more than others

Front 49

• Sodium in the American diet

Back 49

o The typical American diet provides approximately 2300-4700 mg of sodium; over 75% of dietary sodium comes from food processing, with only 10% being added at the table or in cooking. The US Dietary Guidelines for Americans recommend intake below 2300 mg/day for healthy people
Source Example Portion Sodium (mg)
Table salt 6g (1 tsp) 2300
Processed foods American cheese
Muffin
Canned soup
Potato chips
Bagel, oat bran 28g (1 slice)
139g (1 large)
240 ml (1 cup)
50g (1 ¾ oz bag)
89g (4-inch) 300-450
630
700-1200
300-400
450
Smoked foods Ham
Smoked salmon 85g (3 oz)
100g (3.5 oz) 900
665
Pickled foods Dill pickle 65g (1 large) 833
Fast foods Double cheeseburger
Nachos with beef, beans, cheese, etc
Supreme pizza 173g (1 sandwich)

308g (1 large order)

595g (2 slices) 1220

1300

3440
Tip: memorize these values so you can show patients how substituting fresh choices will lower their salt intake

Front 50

• Restricting sodium intake

Back 50

o Sodium restriction is one of the lifestyle modifications recommended by the Joint Committee on the Detection, Evaluation and Treatment of Hypertension
o In many people, keeping sodium intake under 2300 mg/day reduces systolic BP 2-8 mm Hg, which would be expected to lower CVD risk approximately 5-20%. Additional benefit may be seen in some people by reducing sodium to 1500 mg/day (a very low sodium diet which may be difficult for many to achieve unless they avoid processed foods and eating out)
o Salt restriction may help to decrease the doses of medication or may delay the need to medication in mildly hypertensive individuals
o Excessive salt intake appears to increase risk for some cancers, including stomach cancer

Front 51

• Potassium

Back 51

o Hypokalemia may increase blood pressure and risk for stroke. Potassium depletion stimulates renin secretion and has a direct vascular effect: vasoconstriction. Correcting low blood potassium levels will decrease elevated blood pressure.
o Adequate dietary potassium intake helps maintain normal blood pressure. However, studies provide little evidence that potassium supplements lower blood pressure
o Plant foods are an abundant source of dietary potassium. Most people don’t meet recommendations due to low fruit and vegetable intake. Half of US men get less than 3000 mg and half of women get less than 2300 mg.
o Particularly rich sources include:
 Many fruits and vegetables
 Fresh meats
 Milk
o Adequate intake (AI)
 4-8 yrs – 3800 mg/day
 9-13 yrs – 4500 mg/day
 14-18 yrs – 4700 mg/day
 18+ yrs - 4700 mg/day

Front 52

What is some clinical info on potassium

Back 52

• Clinical Information: Diuretic medications are commonly prescribed for hypertension. Some diuretic medications (thiazides, ACE-inhibitors, and angiotensin receptor blockers) are potassium-depleting. Patients using these types of diuretics need extra potassium from foods or sometimes supplements. Aldosterone antagonist diuretics tend to slow potassium losses and increase risk of hyperkalmeia. Diuretic medications (all types) also increase thiamin losses with urine and increase risk of thiamin deficiency.

Front 53

• Calcium

Back 53

o Adequate calcium intake helps maintain normal blood pressure
o Diets that include 2-4 servings (depending on total calorie intake level) of low-fat dairy products have been shown to be effective
o Calcium supplements have not shown the same benefits. These results emphasize the importance of getting adequate calcium from dairy products in the diet on a regular basis to meet the recommendations
o Particularly rich sources include
 Dairy products
 Fortified beverages
 Some green vegetables
o Adequate intake (AI)
 4-8 yrs = 800 mg/day
 9-13 yrs = 1300 mg/day
 14-18 yrs = 1300 mg/day
 19-50 yrs = 1000 mg/day
 50+ yrs = 1200 mg/day

Front 54

What is the DASH study?

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• Clinical Information: The DASH study, Dietary Approaches to Stop Hypertension, was a carefully controlled multicenter feeding trial. The results showed that blood pressure is reduced with an eating plan that emphasizes fruits, vegetables, and 2-4 servings of low-fat dairy products and is also low in total fat, saturated fat, and cholesterol. A standard serving of dairy is 240 ml (1 cup) milk or yogurt, or 45-60 g (1.5- 2 oz) cheese.

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• Magnesium

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o Adequate magnesium intake helps maintain normal blood pressure
o However, evidence is lacking for the effectiveness of magnesium supplements
o A magnesium-rich diet is abundant in whole-grains and plant foods
o Particularly rich sources include
 Whole grains
 Legumes
 Nuts
 Dark green vegetables
 Some fruits
o RDA
 4-8 yrs = 130 mg/day
 9-13 yrs = 240 mg/day
 14-18 yrs = 410 boys and 360 girls
 19-30 yrs = 400 men and 310 women
 31+ yrs = 420 men, 320 women

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• Alcohol

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o Excessive alcohol intake can cause increased arterial pressure and may contribute to stroke. Chronic intake may contribute to or exacerbate hypertension. Hypertensive individuals who drink should limit their daily intake to no more than:
 Liquor: men – 3 oz, women – 1.5 oz
 Wine: men - 10oz, women – 5oz
 Beer: men – 24 oz, women – 12 oz
o Drinking alcohol at higher levels also increases the risk of cancer at many sites, including mouth, esophagus, pharynx, and liver in men and women, and breast in women

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What is some clinical info on ethanol?

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• Clinical Information: Women tend to absorb ethanol more efficiently than men and are more vulnerable to harmful effects. People of lower body weight are more susceptible to the intoxicating effects of a standard drink of alcohol.

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• Obesity

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o Obesity is an independent risk factor for hypertension
o Individuals with excess fat mass have 2 to 6 fold increase in their risk for developing hypertension over normal weight people
o Obesity increases risk for other chronic diseases too. Studies indicate that overweight/obesity increases mortality risk from many cancers, accounting for up to 14% of cancer deaths in men and 20% cancer deaths in women
o Proposed mechanisms for obesity having a causal role in hypertension
 Obesity causes increased salt-sensitivity
 Hyperinsulinemia causes sodium retention and catecholamine release
• Clinical Information: A waist circumference or Waist:Hip that indicates central obesity strongly correlates with risk of hypertension

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• Weight Reduction

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o Weight reduction is associated with decreased blood pressure in hypertensive people
o For every 10 kg (22 lbs) an overweight patient loses, systolic blood pressure will usually decrease 5 to 20 points
o Recommendation: weight management intervention for all overweight patients should be encouraged. Weight loss, along with physical activity, decreases blood pressure and may help improve lipid profiles – both important in cardiovascular risk reduction. Weight reduction and blood pressure studies can be a bit confusing because the weight reduction intervention typically includes a physical activity component. Lack of physical activity may be an independent risk factor for hypertension.
o Tip: Assess a patients readiness to make behavior changes before advising them on what to do. Help them set appropriate goals depending on their readiness to change.
• Clinical Information: Weight loss is often as effective for lowering blood pressure as first-line antihypertensive medication

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• Regular physical activity

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o Regular aerobic physical activity is usually beneficial both for the prevention and treatment of hypertension
o The Joint Committee on the Evaluation, Detection and Treatment of Hypertension recommends regular, aerobic physical activity of at least 30 minutes per day on most days to reduce systolic blood pressure by 4-9 mm Hg
o Physical activity has additional benefits as well in terms of chronic disease prevention. Exercise, which may be vigorous or moderate, is associated with a 50% lower risk of colon cancer. Physical activity also appears to reduce risk of breast cancer, and possibly prostate and endometrial cancer.

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• Other dietary factors

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o Caffeine has only a minor and temporary effect on blood pressure in most people. A small minority is more sensitive and should moderate their intake to one serving per day
o Ensuring adequate omega-3 fatty acid intake is helpful to maintain healthy blood pressure. Increasing intake beyond the AI has not been shown to be beneficial.
 AI: 14-18 yrs – 1.6 g/day for boys, 1.1 g/day for girls
 AI: 19+ yrs – 1.6 g/day for men, 1.1 g/day for women

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• Hypertension management

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o Lifestyle interventions in the management of hypertension focus on 5 areas
Intervention Recommendation Expected Systolic Blood Pressure Decrease
Lose weight, as appropriate Losing excess weight is usually beneficial; strive to reduce BMI below 25 5-20 mmHg for every 10kg weight loss
Obtain regular physical activity Exercise aerobically for 30 minutes/day on most days of the week 4-9 mmHg
Follow a DASH eating pattern Emphasize fruits, vegetables, and low-fat dairy products 8-14 mmHg
Restrict dietary sodium Consume no more than 100 mmol/day (2300 mg) sodium (6g salt) 2-8 mmHg
Limit alcohol consumption Limit alcohol to 2 drinks/day for men and 1/day for women 2-4 mmHg
• These lifestyle modifications should be addressed even if drug therapy is indicated
• Tip: changing behavior, especially eating habits, is difficult for most people. Education is not usually enough. You should invite patients to pick one or two areas to work on at a time, and set realistic behavioral goals. Small steps can lead to permanent behavior change and visible health benefits.

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• The DASH eating plan

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o The Dietary Approaches to Stop Hypertension (DASH) intervention trials found diets high in fruits and vegetables effective for lowering moderately elevated blood pressure (less than 160/95). The addition of low-fat dairy products lowered it even more, as did implementing a sodium restriction.
o Vegetables: fresh, frozen, canned, cooked or raw vegetables, including starchy vegetables – 4-5 servings daily (1 serving = ½ cup cooked vegetables)
o Fruits: fresh, frozen, canned, or dried fruit, and 100% juice – 4-5 daily servings (1 serving = ½ cup canned fruit or 6oz juice)
o Lowfat or fat-free dairy foods: milk, yogurt, frozen yogurt, cheese – 2-3 daily servings (1 serving = 1.5 oz lowfat natural cheese)
o Grains: whole and refined grain products (bread, cereal, crackers, cooked oatmeal, rice or pasta) – 7-8 servings/day (1 serving = 1 slice of bread or ½ cup of pasta)
o Meat, poultry, fish – 2 or less daily servings (1 serving = 3 oz cooked meat)
o Nuts, seeds, dry beans – 4-5/week (1 serving = 1/3 cup nuts or ½ cup cooked beans)

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• Following a DASH diet

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o Use 2300 mg sodium
o Tip: although some patients respond to pre-set menus, most will benefit from dietary counseling more tailored to their individual preferences

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• Treatment algorithm

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Blood Pressure Classification Systolic (mm Hg) Diastolic (mm Hg) Treatment Approach
Normal Less than 120 Less than 80
Prehypertension 120-139 80-89 Lifestyle modification; add drug therapy if compelling reason such as chronic kidney disease, diabetes, or heart failure
Stage 1 hypertension 140-159 90-99 Lifestyle modification and drug therapy
Stage 2 hypertension 160 and above 100 and above Lifestyle modification and drug therapy

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• Thrombus formation

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o Atherosclerotic plaques attract and activate blood platelets
o Both endothelial lesion and activated platelets can trigger blood coagulation
o Anything that reduces platelet aggregation and thrombosis can reduce risk of MI; some types of dietary fat have this ability

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• Marine oils and CVD Prevention

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o Marine oils influence thrombosis risk
o From a 1998 research report: eating cold-water fish at least once a week could cut the chances in half of dying suddenly from heart failure. Researches followed more than 22,000 male physicians for 12 years and found those who ate at least one serving of cold-water fish/week reduced their chances of cardiac arrest by 50%. Researchers say omega-3 fatty acids eaten with cold water fish appear to protect the vascular endothelium in coronary and peripheral arteries
o Cold water fish contain an abundance of highly unsaturated fatty acids. Their survival depends on this, because other, more saturated, fats would be solid at their very low body temperatures
o Advise healthy people to consume fatty fish about 2/week (contains DHA and EPA). The bulk of omega-3 fatty acids is alpha-linolenic acid (ALA) from seeds, oils, and vegetables. In combination, those two sources need to provide the recommended amount of 1.1 g/day (women) and 1.6 g/day (men)
• Clinical Information: Patients with established heart disease should aim to get at least 1g/day of the long-chain omega-3 fatty acids EPA and DHA combined. Supplementation with even higher doses of concentrated fish oils has been useful for the treatment of hypertriglyeridemia

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• Omega-3 fatty acids and cardiovascular risk

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o Omega-3 fatty acids reduce cardiovascular risk because they:
 Reduce elevated serum triglycerides
 Moderate tachycardia and arrhythmia
 Inhibit platelet aggregation and formation of blood clots
 Lower blood pressure
 Prevent plaque formation in coronary arteries

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• Omega-6 vs. omega-3 fatty acids

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o The 3-series eicosanoids tend to be less active in promoting platelet aggregation, inflammation, and vascular muscle contraction than the 2-series eicosanoids that are derived from omega-6 fatty acids
o A 4oz serving of fatty cold water fish will provide several hundred mg of the very long chain fatty acids EPA and DHA; the fattiest fish, salmon, mackerel, and herring, may provide more than a gram per meal
o Omega-6 fatty acids (good sources: safflower oil, soybean oil, sunflower oil, canola oil)  eicosatrienoic acid (20:3omega6)  1-series eicosanoids
o Omega-6 fatty acids  arachidonic acid (20:4omega6)  2-series eicosanoids
o Omega-3 fatty acids (good sources: linseed oil, marine oils)  eicosapentaenioic acid (20:5omega3)  3-series eicosanoids

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• Coagulation cascade

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o Factor VII is an important cardiovascular risk factor. Habitual high fat intake can increase factor VII activity.

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• Vitamin K and antibiotics

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o Blood coagulation is initiated and promoted by a cascade of reactions, balanced by several specific inhibitors of these reactions. Factors II, VI, IX and X and proteins C and S are vitamin K-dependent proteins produced in the liver. Some vitamin K is produced by intestinal bacteria, and a small proportion of this is usually absorbed. Oral antibiotics may suppress bacterial vitamin K production in the terminal ileum and colon.
o When antibiotic users have low dietary vitamin K intakes at the same time, they may have too little vitamin K to make functioning coagulation factors. Some people start bleeding when they are given antibiotics
o Good dietary sources of vitamin K are cooked greens and green vegetables

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• Vitamin K and Warfarin

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o Patients with mitral valve damage or artificial heart valves are commonly anticoagulated with compounds that inhibit vitamin K activity (coumadins) to reduce the risk of thrombus formation.
o Thrombi are dangerous because they may occlude a vessel, like the pulmonary, coronary, or cerebral artery, that supplies a major organ

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• Vitamin K intake and anticoagulation therapy

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o Short-term changes in vitamin K intake rapidly alter the effectiveness of antivitamin K anticoagulation therapy. Patients do not need to avoid foods rich in vitamin K completely, but they should maintain a consistent intake and not make sudden changes to their diet
o The main sources of vitamin K in the diet are:
 Cooked greens (spinach, kale, collards, mustard, turnip)
 Broccoli
 Brussels sprouts
 Canola and soybean oil

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• Vitamin K and arterial calcification

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o Vitamin K’s role in arterial calcification
 Several proteins involved in control of arterial calcification are vitamin K-dependent. Vitamin K status may be important in slowing atherosclerosis when calcification decreases the elasticity of arteries

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• Elevated homocysteine

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o An important cardiovascular risk factor
o Many patients with symptomatic atherosclerosis have such elevated concentrations
o Increased levels are most often caused by a combination of
 A genetic variant of an enzyme in homocysteine metabolism
 Suboptimal nutrition status of folate, vitamin B12, B6, or riboflavin
o With adequate vitamin intakes, the high homocysteine levels often normalize, and cardiovascular risk decreases
• Clinical Information: Recent clinical trials indicate that very high intake of vitamin B6 may actually increase CVD risk, underscoring the importance of obtaining an appropriate, but not excessive, intake.

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• Folate

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o Food sources of folate
 Fortified ready-to-eat cereals
 Enriched grains (bread, pasta, rice)
 Green leafy vegetables
 Dried beans
 Citrus fruits
 Orange juice
o Fortified and enriched products contain folic acid, the synthetic form of folate. Folic acid is more bioavailable than the naturally-occurring food folate.
o Natural food folate = folylpolyglutamate
o Synthetic folate = free folic acid
o People concerned about getting too much folate from fortified food should know: there are no adverse effects from consumption of food sources; caution is based on concerns of excess folate worsening vitamin B12 deficiency; cereals enriched with folate also provide vitamin B12

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• Homocysteine from methionine

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o As a methyl group is transferred from SAM to one of many possible acceptors, S-adenosylhomocysteine is generated, and from this, homocysteine.
o Homocysteine is therefore the normal part of a vitally important process
o Methioine  SAM  S-adenosylhomocysteine  homocysteine

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• Homocysteine to methionine

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o Homocysteine can be converted back into methionine in a reaction that requires 5-methyltetrahydrofolate. This reaction keeps homocysteine concentrations in blood and tissues at low levels

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• Vitamin B6 and homocysteine

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o An alternative pathway for the metabolism of homocysteine is a reaction catalyzed by cystathionine beta-synthase:
 Homocysteine condenses with serine to form cystathionine
 Cystathionine then releases cysteine, alpha-ketoglutarate, and an ammonium ion.
o Both of these reactions are vitamin B6 dependent
o Vitamin B6 status has been related to homocysteine levels in some population studies

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• Homocystiene and CVD risk

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o Current data indicate that a 25% lower homocysteine level is associated with an 11% lower ischemic heart disease risk and a 19% lower stroke risk
o Mandatory folate fortification of grains in the US has reduced the average homocysteine level of the general population but a solid link with fewer deaths from CVD has not yet been seen
• Clinical Information: Adequate folate status also has been shown to reduce the risk of bearing a child with neural tube defect, having anemia, and getting colon cancer. As of January 1998, most grain products in the US are fortified with at least 140 micrograms/100g food. For an average woman this will mean an additional intake of about 100 micrograms of highly bioavailable folate. The RDA for folate is 400 micrograms/day for most adults. Women who could become pregnant should get this amount from dietary supplements.

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• Toxic effects of homocysteine

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o Toxic effects of homocysteine in tissue and circulating blood include
 Direct endothelial cell damage
 Increase of cholesterol oxidation
 Oxidative modification of apolipoproteins
 Promotion of platelet adhesion and aggregation
 Scavenging of NO and inhibition of vascular motility

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• NO effects

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o Homocysteine readily reacts with NO, decreasing the availability of this important mediator and smooth muscle relaxant in the arterial wall.
o NO maintains a low level of stimulation in platelets and thereby reduces the tendency of platelets to aggregate and adhere to vascular endothelium.
o Decreased NO concentration in platelets may explain how high homocysteine levels in blood promote venous and arterial thrombosis