Kidney disease and cardiovascular risk
Kidney disease prevention is covered in detail in another section of this website: Preventing kidney disease. However, it is important to mention here that reduced kidney function, especially if it is associated with passing protein in the urine, is a major risk factor for both cardiovascular disease and premature death. This increased risk is proportional to the severity of the kidney impairment, with about 50% of people with end-stage kidney disease dying from cardiovascular disease (heart attacks).
A common cause of kidney disease in Australia is diabetes. In people with diabetes and kidney failure, the risk of dying from cardiovascular disease compared to people without either condition is 40 times greater.
People with severe kidney problems are automatically classified as being at high risk of cardiovascular disease (i.e. they have a 15 per cent or greater risk of having a ‘cardiovascular event’ in the next 5 years.)
Unfortunately early kidney failure is common in Australia and many people are unaware they have the problem. About 11 per cent of Australian adults (1.8 million people) have moderate to severe kidney failure and may be at risk of developing end-stage renal failure.
Early kidney disease has few symptoms and therefore often goes undiagnosed. (About 500,000 Australians have undiagnosed and therefore untreated early kidney failure.)
For the above reasons, it is important that:
- people with impaired kidney function have their risk factors aggressively managed and that they achieve optimum blood pressure and cholesterol levels.
- people who have other risk factors for vascular disease are screened for kidney disease. Luckily screening for kidney impairment is now usually done with most routine blood screening tests. (See notes on the eGFR in the section on kidney disease.)
Polycystic Ovarian Syndrome
Polycystic ovarian syndrome (PCOS) is the most common hormonal abnormality in women, affecting about 5% to 10%. Unfortunately, it also significantly increases a woman's risk of suffering from diabetes and obesity, and this associated increased incidence of diabetes and obesity mean that it also increases the risk of heart attacks.
While PCOS is today a well-recognised condition, this was not the case in the past and many women over 40 with the condition may still be unaware that they have it. This means that they are also unaware that they are at increased risk of diabetes and heart attacks, which is a concern as they are in the age group that these conditions start to become a problem.
PCOS is mainly caused by excessive secretion of androgens (male hormones) by the ovaries and increased insulin resistance (the main cause of type 2 diabetes), although other hormone abnormalities are also present. Symptoms usually begin around puberty and the condition continues past menopause. It is inherited to a significant degree with about 30% of mothers and sisters of sufferers also having the condition.
Symptoms
PCOS is characterised by the following symptoms (although not all are present in every woman with the condition):
- Hirsutism (or excessive hair growth) (PCOS is the most common cause of this symptom.)
- Male pattern hair loss
- Acne
- Irregular, often less frequent menstrual periods; and in some women no periods ocur (amenorrhoea).
- Reduced ovulation (egg release) and thus reduced fertility. Most women with PCOS can successfully use medication to induce ovulation and become pregnant. Women with PCOS still need to take contraception to prevent unwanted pregnancy.
- Excessive weight gain / obesity
- Cysts on the ovaries (usually diagnodsed by abdominal ultrasound investigation)
Importantly, it is associated with other serious illnesses including:
- Lipid abnormalities, including high triglycerides, high LDL cholesterol and sometimes a low HDL cholesterol.
- Insulin resistance that often leads to pre-diabetes conditions or actual diabetes. (By age 40, about 30% of women with PCOS have a pre-diabetes condition and about 10% have developed diabetes. The incidence of these conditions continues to rise with age and they are more likely in women who are overweight and in women in ethnic groups that have an increased incidence of diabetes.) Diabetes during pregnancy is also more common in women with PCOS.
- Increased risk of vascular disease (heart attacks and strokes), mainly due to the above mentioned problems.
- A higher incidence of uterine (womb) cancer
Diagnosis - Finding cysts on ovaries is not sufficient to make the diagnosis of PCOS.
While most (but not all) women with PCOS do have polycystic ovaries (i.e. polycstic ovaries), about 20% to 25% of all adult women have cysts in ovaries on ultrasound examination; that is, three times the number who have PCOS. Thus, the majority of women who have polycystic ovaries do not have PCOS and, not surprisingly, do not have clinical symptoms of the syndrome. For this reason, diagnosis of the PCOS should not rely solely on finding polycystic ovaries. Rather, a woman is considered likely to have PCOS if she has two of the following three features.
- Irregular menstrual periods (usually from puberty). This is a very important symptom.
- Evidence of excessive androgen secretion. This can be demonstrated either by the presence of symptoms of excessive androgen secretion (acne, hirsutism or male pattern hair loss) or by elevated blood levels of androgens.
- The presence of polycystic ovaries on ultrasound testing.
Several other hormonal abnormalities can mimic PCOS and it is important that they are excluded before making the diagnosis. (This is done by a combination of assessment of patient symptoms and blood tests.) These conditions include late-onset congenital adrenal hyperplasia (measurement of 17-hydroxyprogesterone), thyroid abnormality (measure thyroid-stimulating hormone), hyperprolactinaemia ( measure prolactin) and Cushing’s syndrome.
Testing for diabetes at diagnosis and regularly thereafter is usually recommended for women with PCOS. This is usually done by doing a fasting blood glucose test.
Treatment
The mainstay of treatment for the condition is consuming a healthy diet and doing adequate exercise with the aim of achieving and maintaining a healthy weight.
Irregular menstrual periods can be treated with the combined oral contraceptive pill and insulin resistance can be treated, when necessary, with the medication metformin.
Women with the condition should also consider ensuring that they pay careful attention to minimising their other risk factors for heart attacks.
Depression
In the past it has been felt that stress and Type A personality (anxious, ‘highly driven’ people) causes coronary artery disease. There has been to date little concrete evidence to support this theory.
Depression has also been implicated in causing cardiovascular disease; although a recent analysis of all the information on this topic has questioned this association. Certainly there is little evidence that treating existing depression decreases the person’s cardiovascular risk. (However, treating depression certainly improves the person’s quality of life and is likely to improve their motivation to address other cardiovascular risk factors.)
Raised homocysteine levels
Homocysteine is an amino acid that occurs naturally in the body. Increased levels are due to abnormalities in the way homocysteine is metabolised and are associated with an increased incidence of coronary artery disease. Homocysteine causes injury and inflammation in the lining of the vessel walls, helping cholesterol gain entry. It may also increase blood clotting.
Mildly raised levels of homocysteine are relatively common, occurring in up to 10 per cent of the population. High levels are relatively rare and occur in classical homocysteinuria, which is an inherited deficiency in the enzyme cystathionine-b-synthetase. In severe cases (i.e. the homozygous state where the genetic abnormality is present on both members of the affected pair of chromosomes), 50 per cent of those affected have significant vascular problems by age of 30 years. Less severe cases (i.e. the heterozygous state, where the genetic abnormality is present on one member of the affected pair of chromosomes) are associated with only slightly elevated homocysteine levels.
Homocysteine levels can be measured by a blood test. At present, there is no evidence to support routine screening for this condition and testing should be limited to patients with unexplained vascular events, such as a heart attack with no obvious risk factors, especially if the person is young or has a strong, unexplained family history of coronary artery disease.
Lowering homocysteine levels – No shown beneficial effect
Reducing homocysteine levels can be achieved through supplements of vitamin B6 (25-50mg/day) and folic acid (0.5mg/day). Vitamin B6 acts as a co-factor (a helper substance) for the enzyme cystathionine-b-synthetase(CbS) which breaks down 50 per cent of homocysteine. A form of folic acid acts as co-factor in the conversion of the remainder of homocysteine to other compounds.
Unfortunately, research that has been conducted into whether dietary folate supplements help reduce vascular disease in the general population have to date shown that such supplements have no beneficial effect in reducing vascular diseases such as heart attacks.
Lipoprotein (a)
Higher than normal blood levels of lipoprotein (a) increase coronary artery disease by increasing atheroma lesions and by helping prevent clot breakdown. Lipoprotein (a) levels are genetically determined and vary little throughout life. High levels can triple the risk of coronary artery disease. If your family has a high incidence of coronary artery disease, it may be worth considering having your level checked to see if this is a contributing cause. The only effective treatment available at present is very high doses of nicotinic acid but it is not used as at this dise all patients get a very significant skin rash. Thus, a raised level is best addressed by reducing other risk factors for vascular disease treated more vigorously. It is paticularly important to protect kidney function as lipoprotein (a) increases as kidney function deteriorates. Other medications that may prove useful are presently being trialled.
Factors that increase clotting
Factors that increase the blood’s likelihood also increase the risk of heart attacks and strokes. They include:
- Smoking
- Polycythaemia, a medical condition which causes an increase in the density of red blood cells in the blood.
- Hormone replacement therapy. The female hormones oestrogen and progesterone, which are used in some women to help treat the symptoms of menopause, can increase the risk of heart attacks slightly.
- Oestrogen-containing oral contraceptive pills. The risk of heart attacks and strokes associated with the use of the oral contraceptive pills that contain oestrogen is very small in most women and certainly much less than the risks associated with an unplanned pregnancy. However, the risk level is considerably higher in some women and these women need to consider using alternate forms of contraception. They are women who are over 35 years of age and have any of the following:
- Smoke (This is a very important factor and women over 35 who smoke should not be on an oestrogen-containing oral contraceptive pill.)
- High blood pressure
- A high overall risk of heart attacks due to other risk factors, such as a very high cholesterol leve
Factors that decrease clotting can reduce the likelihood of heart attacks occurring. (Their effect on strokes varies as it will reduce the likelihood of strokes due the artery disease but increase the risk of strokes due to haemorrhages. See section on ‘Heart Attacks and Stroke – General information') Factors that reduce clotting include:
- Aspirin
- Other anti-platelet drugs, such as clopidogrel.
- Fish oils
Antioxidants
Many compounds, including LDL (bad) cholesterol, can exist in an oxidized or an oxidized state. This can affect the nature of the compound and its actions. LDL cholesterol is one such compound and when it is oxidized it is more likely to cause cholesterol to accumulate in vascular lesions, thus hastening the progression of vascular diseases such as heart attacks. (The oxidation of tissue lining artery (blood vessel) walls has a similar effect.)
Oxidants are chemicals in the blood that cause this oxidation of another compound, such as the oxidation of LDL cholesterol. (Some oxidants are produced as a by-product of the body’s metabolism; others are introduced to the body from outside. For example, cigarette smoke contains oxidant chemicals.)
On the other hand, antioxidant compounds can help prevent oxidation and thus the formation of oxidized LDL cholesterol. They can also reverse the oxidation process and convert already oxidized LDL back to the unoxidised form. Thus antioxidants act to reduce vascular diseases such as heart attacks.
Foods naturally rich in antioxidants (mostly in fruit and vegetables) are known to be beneficial with respect to the prevention of cardiovascular disease and cancer and their consumption should be encouraged. (People who have the lowest consumption of antioxidants have roughly a 15% higher incidence of heart attacks compared to those consuming the most antioxidants.) Flavanoids, available in apples, onions, tea and red wine are particularly beneficial.
Unfortunately, antioxidant supplements have not been shown to achieve the same beneficial effects. This is probably because they do not provide the complex variety of antioxidants that a wide variety of foods contain.
Alcohol
Discussing the health benefits of alcohol is somewhat of a paradox as, apart from tobacco, alcohol causes more physical and mental illness than any other drug or substance. Particularly underestimated are the less obvious behavioural effects that excess alcohol has on many people, often on a daily basis. These include workplace injury and under performance, and the changes in personality that are so detrimental to long-term personal relationships.
It must therefore be stressed that any overall benefit relates to the consumption of minimal quantities of alcohol. One to two standard drinks per day is optimal (10 to 20g of alcohol) and any intake above two drinks per day (20 grams) has no overall beneficial affect and is probably causing overall harm.
Another factor to consider is that any consumption of alcohol, even just one drink per day, increases the risk of cancer and this increased risk rises in proportion to increase in consumption. (This is especially the case for women as increased breast cancer risk is an significant consequence of female alcohol consumption.)
With these limits in mind, there is evidence that low-level consumption has beneficial affects for vascular disease (heart attacks and strokes) in men, especially when the alcohol is taken with food. The evidence for this effect is however not strong and certainly non-drinkers should never take up alcohol consumption hoping for a beneficial health effect. The evidence of benefit is less (if any) for women because compared to men:
- Women suffer less from heart attacks and strokes
- Women have a greater increase in cancer risk from alcohol consumptionthan men
Alcohol on its own has several effects that could explain its possible benefit regarding reducing vascular disease. These include increasing HDL cholesterol and reducing clotting (by its anti-platelet activity).
Red wine has the added benefit of possessing antioxidants (polyphenols and anthocyanins). These antioxidants are the red pigments from the grape skins and they may help reduce vascular disease by preventing the oxidation of LDL and reducing clot formation. White wine and beer also have antioxidants but to a much lesser extent.
On the other hand, any alcohol intake increases blood pressure in proportion to intake and higher intakes increase the incidence of strokes.
Recently, the accuracy of the evidence used to substantiate the benefits mentioned above has been questioned. This is because, when assessing people who did not consume any alcohol, some studies did not differentiate between people who chose not to consume alcohol and people who had ceased consumption for medical reasons.
Non-steroidal anti-inflammatory drugs (arthritis drugs)
Recent evidence suggests that most of the drugs commonly used for the treatment of arthritis (with the exception of aspirin) increase the risk of angina or heart attacks occurring. While the evidence for this association is not definite, it is wise for people who have a past history of heart attacks or angina or have a high risk of developing these conditions to avoid using arthritis medications; at least until further research clarifying the situation is produced.
Infection
It is not uncommon to find bacteria such as Chlamydia pneumoniae and Heliobacter pylori in vascular lesions in the coronary arteries and it is possible that such bacteria could act to weaken the vascular lesion, making it more likely to rupture and cause a heart attack. There is also some evidence to suggest that people with significant infective gum disease have an increased risk of having a heart attack.
To date the only study using antibiotics to try to prevent heart attacks did not demonstrate any beneficial effect. More study is being done on this topic.
Additional beneficial dietary influences on vascular disease
In addition to the foods already mentioned, studies have suggested that other foods are also beneficial with regard to reducing vascular disease. These are shown in the table below. It needs to be stressed that studies examining the effects of specific dietary components are very difficult to conduct and recommendations from such studies can rarely be made with great certainty.
Food |
Effects / Comments |
Vegetables and fruit |
|
Nuts |
|
Tea |
|
Soy products |
|