Nutritional Recommendations for the Management of Feline Cardiopathy

3. Nutritional Recommendations for the Management of Feline Cardiopathy

While little information is available in the literature on the specific nutritional requirements of cats with cardiac diseases, several general recommendations can be provided by extrapolating from other species and considering the metabolic peculiarities of cats.

Equate Energy Density of the Diet to the Cat’s Body Condition

The body condition score of cats with cardiopathy is highly variable. Maintaining optimal condition in these patients is one of the major goals of dietary treatment.

Cachexia

Severe weight loss and muscle wasting is less common in cats than in dogs with cardiopathy. (Freeman, 2000). "Cardiac cachexia" does not generally appear until advanced stages of heart failure and can be associated with very rapid muscle atrophy. The myocardium is not protected from general protein catabolism, in addition to lower immune defenses and generalized weakness, "cardiac cachexia" may also contribute to the progression of heart failure.

"Cardiac cachexia" is multifactorial: anorexia,increased energy requirements, metabolic alterations, poor blood perfusion of the tissues, as well as complication of renal failure, either primary or secondary to cardiovascular disease all contribute (Figure 16).

Figure 16. Cachexic cat with chronic kidney disease and systemic arterial hypertension. (systolic BP = 170 mmHg) Cats with cardiac disease have many reasons for not eating. Aside of the weaknesses associated to the disease, drugs prescribed in this condition may induce nausea and the dietary restrictions commonly found in therapeutic diets (e.g., low protein and low sodium) may produce a diet that is not very palatable. (© Valérie Chetboul).

Spontaneous food consumption must thus be encouraged in cats with cachexia, by feeding palatable diets (see below recommendations on protein and sodium levels), presenting frequent small meals and warming wet foods to name a few. In order to reduce the volume of the meals, the energy density of the diet should be increased (e.g., higher fat and lower fiber levels).

Overweight Cats

Around 35% of the cats presented to veterinarians are overweight (Lund et al., 2006). Whatever the species, obesity is associated with an increased cardiovascular risk. Caloric restriction to induce weight loss in obese cardiac cats is desirable and more so if the cat is exercise intolerant.

Studies in rodents have found that long term energy restriction reduces oxidative stress and protects against several degenerative diseases including cardiomyopathies (Kemi et al., 2000; Guo et al., 2002). To our knowledge, such a study has not been conducted on cats.

Provide Protein and Amino Acids to Fight Cachexia and Promote Food Intake

It has long been recommended that animals with heart failure should be fed diets with reduced protein levels to protect renal function, as renal and cardiac diseases are often linked (McClellan et al., 2004; Nicolle et al., 2007). Those recommendations are now clearly outdated (see chapter 7). Moreover cats, because of their true carnivorous nature, have high protein requirements and their metabolism cannot adapt to low protein intakes. Restricting protein simply increases the risk of "cardiac cachexia" and exercise intolerance. Food for cats with cardiac disease must therefore contain at least the minimum protein requirement (60 - 70 g protein/1000 kcal) (Freeman, 2002).

Taurine Supplementation

The essential requirement for taurine to insure normal cardiac as well as other functions in cats has been discussed above.

Studies have shown that dietary taurine supplementation increases the taurine concentration in the myocardium of both healthy cats and cats with heart failure (Fox & Sturman, 1992). Bearing in mind taurine’s protective and positive inotrope roles with respect to cardiac function, taurine supplementation may thus be encouraged, whatever the type of cardiopathy. The recommendation is in the range of 625 mg/1000 kcal (Freeman, 2002).

There is a reciprocal relationship between taurine and potassium requirements. Taurine slows the loss of potassium through the cell, while potassium prevents the loss of taurine by the myocardium. Taurine supplementation (> 625 mg/1000 kcal) could therefore be beneficial to cats with potassium deficiency, e.g., those with impaired renal function (Dow et al., 1992).

Dietary Arginine

Contrary to other species, cats are unable to synthesize arginine. Arginine must therefore be provided by the diet. Furthermore, the cat’s high-protein requirement necessitates high arginine requirements due to its involvement in the urea cycle for ammonia detoxification.

Arginine is a nitric oxide (NO) precursor (Figure 17). NO is produced by the vascular endothelium and acts as a blood vessel myorelaxant. NO thus helps regulate blood pressure. In humans and rodents, arginine supplementation has been shown to increase NO production (Lerman et al., 1998).

NO also has an antithrombotic effect (Moncada et al., 1991). A study reported that cats with HCM and associated thromboembolism presented with lower levels of circulating arginine than healthy cats or cats with an uncomplicated cardiomyopathy (McMichael et al., 2000). Arginine supplementation may therefore have beneficial effects in this condition although this has yet to be proven. The NRC recommends a level of at least 1.93 g/1000 kcal in healthy cats. The optimum range required in patients with heart disease has yet to be determined.

Figure 17. Origin of nitric oxide.

Benefits of Long-chain Omega-3 Fatty Acids (EPA/DHA)

The composition of dietary fats (especially the ratio of unsaturated omega-6 to omega-3 fatty acids) influences membrane fluidity as well as other hemodynamic factors. In cardiology, many studies have been conducted on the potential role of omega-3 fatty acids. In humans and dogs, much lower plasma concentrations of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-6) have been shown, regardless of the underlying cardiac disease (Freeman et al., 1998). While few studies have been conducted on cats, the properties of omega-3 fatty acids deserve some attention.

Linseed oil contains high levels of a-linolenic acid but this is only a precursor of EPA and DHA, and the ability of cats to convert a-linolenic acid to EPA/DHA is very limited (Figure 18). Only fish oils are good sources of EPA and DHA. Cod liver oil should not be used due to its high levels in vitamins A and D.

Figure 18. General pathway of long chain omega-3 and omega-6 fatty acids synthesis.

On usual diets, cell membranes contain very low concentrations of long chain omega-3 fatty acids, but these can be increased with a food that is supplemented with fish oil. For example, with a supplementation of 180 mg DHA and 117 mg EPA/cat/day over a 4 week period, the level of EPA in the plasma phospholipids increases by 70% while the DHA levels increased by a factor of 3.4 (Filburn & Griffin, 2005). Dietary enrichment with EPA and DHA can facilitate membrane peroxidation by free radicals (Meydani et al., 1991) but this adverse phenomena can be minimized by adjusting the levels of dietary vitamin E.

Antithrombotic Action

Long chain omega-3 fatty acids are known for their antithrombotic activity. This could be highly beneficial for cats, a species in which platelet activation is easily triggered (Welles et al., 1994). Increasing the omega-3 fatty acids (1.03 g/kg diet vs 0.07 g/kg in the control diet) and decreasing the omega-6 fatty acids (1.20 g/kg vs 1.34 g/kg in the control diet) reduces platelet aggregation and activation in healthy cats by day 112 (Saker et al., 1998). This benefit has yet to be confirmed in cats with HCM.

Anti-inflammatory Effect

In rodents, increasing the level of long chain omega-3 fatty acids in the fat content of food reduces the production of 2 and 4 series eicosanoids from arachidonic acid, which have a pro-inflammatory action (Broughton & Wade, 2001). On the other hand the production of anti-inflammatory 5 series leukotrienes (LT) is stimulated.

In humans with heart failure, long chain omega-3 fatty acids reduce the production of "inflammatory cytokines", TNFα and IL-1 (Levine et al., 1990). These cytokines contribute to cardiac cachexia by increasing energy requirement and muscle catabolism (Mahoney & Tisdale, 1988). Moreover, by regulating the expression of proteosomes, EPA inhibits the loss of lean mass (Whitehouse et al., 2001).

In dogs with cardiac disease, supplementation of EPA (27 mg/kg weight/day) and DHA (18 mg/kg weight/day) improves dietary consumption, reduces the production of inflammatory cytokines and so reduces cachexia (Freeman et al., 1998). To our knowledge, no information with respect to cats with cardiac disease is available at this time.

Anti-arrhythmogenic Effect

Several studies have shown a benefit of EPA and DHA in the management of cardiac arrhythmia in rodents and dogs (Kang & Leaf, 1996; Charnock, 2000; Smith et al., 2007). The mode of action relies on the ability of long chain omega-3 fatty acids to modulate the sodium and calcium flows inside the myocytes (Gerbi et al., 1997).

Arrhythmia is often one of the first signs of feline HCM. Based on observations in other species EPA and DHA supplementation could thus be recommended at early stages of cardiopathy but, to our knowledge, no information on this subject is available at this time.

Regulating Endothelial Function

EPA and DHA are involved in the regulation of endothelial function, probably by modulating NO production (Kristensen et al., 2001). In humans, supplementation induces a vasodilatation effect (Kenny et al., 1992). Very high doses (>3 g/day) even led to a fall in BP in hypertensive individuals (Kris-Etherton et al., 2002). Studies in cats with cardiac disease are thus needed.

Omega-3 Fatty Acids, Ratio Versus Absolute Intake and Doses

There is an ongoing debate about whether the dose of omega-3 fatty acids or rather the omega-6 to omega-3 ratio is most important to producing the beneficial effects of omega-3 fatty acids (NRC, 2006). Some results suggest that the total dose of omega-3 is important, although the ratio (n-6/n-3) must also be kept as low as possible to promote the anti-inflammatory effect of omega- 3 fatty acids (Grimm et al., 2002). In light of the results obtained in humans, it appears reasonable to recommend tripling the traditional recommended quantity of omega-3 fatty acids in healthy cats to at least 0.06 g/day, corresponding to a concentration in the food of 0.10 - 0.35 g/1000 kcal (Freeman, 2002).

Monitor Mineral Balance

Sodium and Chloride

It is usually recommended to feed cardiac patients a very low sodium diet. There is evidence in dogs, however, that this restriction would not be beneficial especially at early stages of heart disease. Indeed, low Na diets will activate the renin-angiotensin-aldosterone system, while the purpose of medical treatments for heart disease is to inhibit it. Sodium restriction (up to 0.5 g/1000 kcal) is thus only justified when an advanced stage of congestive heart failure is reached.

Studies on the influence of sodium in cardiac patients use salt (NaCl) as the source of dietary sodium. It is therefore impossible to differentiate between the respective influences of those two elements. Some data in rats indicate that chloride can also influence plasma renin activity (Kotchen et al., 1980). Therefore, current knowledge does not go further than recommending observance of a moderate dietary chloride level.

Potassium

Potassium is an intracellular electrolyte whose plasma concentration must be monitored in cardiac animals undergoing medical treatment (although the plasma level is not a good reflection of body reserves). Hypokalemia can occur when diuretics are prescribed (e.g., furosemide) and in the event of CKD. The symptoms associated with hypokalemia are muscle weakness and bradycardia (Linder, 1991). Hypokalemia will also potentialize digoxin toxicity. As mentioned before, there is a reciprocal relationship between taurine and potassium. Thus, it appears sensible to advise both potassium and taurine supplementation in cats with hypokalemic cardiopathy.

Angiotensin-converting enzyme inhibitors (ACEI) are often used in the management of cardiopathy in both humans and animals. In theory they could promote hyperkalemia by stimulating potassium renal reabsorption (Lefebvre et al., 2007). In practice, hyperkalemia, is minimized by the prescription of furosemide and appears negligible in animals (Lefebvre et al., 2007). Extended administration of ACEI has not been associated with hyperkalemia in dogs (Pouchelon et al., 2004). Dietary potassium levels in cats with cardiac disease should thus be similar to those for adult maintenance (1.5 - 2 g/1000 kcal) even when treated with ACEI.

Magnesium

Magnesium is a cofactor in hundreds of enzymatic reactions involving carbohydrate and lipid metabolism. The activity of the heart muscle is dependant on the right balance between magnesium and calcium. Magnesium therefore plays an important role in normal cardiac function and magnesium deficiency is implicated in many cardiopathies across species (Rush et al., 2000; Gottlieb et al., 1990).

Diuretics may promote urinary losses of magnesium, and thus the risks of low magnesium status causing arrhythmias and reduced cardiac output. Plasma magnesium is a poor indicator of body reserves and hypomagnesemia is rare in practice (Freeman, 2000). A study on hospitalized cats found no significant alteration of magnesium status associated with cardiopathies (Toll et al., 2002). Magnesium supplementation in HCM cats did not result in clear clinical benefit (Freeman et al., 1997). There is thus no evidence to date to recommend dietary magnesium levels above those necessary for adult maintenance (0.12 - 0.25 g/1000 kcal) for cats with cardiac disease.

Phosphorus-calcium Balance

Due to the common association between cardiopathy and renal disease (McClellan et al., 2004; Nicolle et al., 2007), dietary phosphorus levels should be limited to minimize secondary hyperparathyroidism (see chapter 7).

Reverse Any Deficiencies

B Group Vitamins

Cats naturally have high B vitamin requirements (Burger, 1993). B vitamin deficiencies (Table 4) in cardiac patients result from anorexia and increased urinary losses secondary to the use of diuretics (Rieck et al., 1999).

Plasma vitamin B6 and B12 concentrations are significantly lower in cats with HCM than in healthy cats (McMichael et al., 2000). A correlation was found between plasma B6, B12 and folic acid concentrations and the size of the left atrium. The role of these vitamins in the development of HCM (primary or secondary) has yet to be clarified, however.

Based on the evidence, cats with cardiac disease probably have higher B vitamin requirements than healthy cats. Diet for cats with cardiac disease should thus contain two to three times the levels recommended for adult maintenance.

L-carnitine

L-carnitine is a quaternary amine synthesized in the liver from lysine and methionine (Figure 19). It is present in all striated muscles, but the myocardium contains 95% of the body reserves. Its main role is transporting long-chain fatty acids into the mitochondria, where they are oxidized to produce energy.

Figure 19. Carnitine molecule.

DCM associated with carnitine deficiency has been described in humans and some dog breeds such as the Boxer, Doberman and Cocker Spaniel (Brevetti et al., 1991; Helton et al., 2000; Keen et al., 1991).

It has been suggested that HCM could be associated with abnormal fatty acid metabolism. Therefore, L-carnitine could be beneficial in avoiding the intracellular accumulation of fatty acids in the myocardium (Lango et al., 2001). In humans, L-carnitine supplementation (3 - 4 g/day) in combination with lower long-chain fatty acid intakes improves the clinical status of HCM patients (Bautista et al., 1990). This has yet to be demonstrated in cats.

To Strengthen the Antioxidant Defenses

The role of antioxidants in the prevention and treatment of human heart diseases has been extensively studied. Free radicals are the by-products of oxygen metabolism, against which the body defends itself by producing endogenous antioxidants. An imbalance between oxidants and antioxidants (oxidative stress) may increase the risk of cardiopathy (Figure 20). Antioxidants can also be provided in the diet. The main antioxidants are enzymes (superoxide dismutase and its cofactor copper, catalase, as well as glutathione peroxidase and its cofactor selenium) and free radical scavengers (vitamin E, vitamin C, glutathione, taurine, carotenoid pigments). Current research is also focused on new classes of antioxidant such as polyphenols.

 
Figure 20. Origin of oxidative stress.

Some antioxidants will now be reviewed but it is important to remember that synergy can be observed by using a mixture of antioxidants. Different antioxidants will also be located in different areas of the cell (membrane, intracellular organelles and nucleus).

Vitamin E

The antioxidant effect of vitamin E (α-tocopherol) has been the subject of studies for many years. In the cardiovascular domain many studies show its beneficial role, especially via two particular effects:

- It maintains endothelial tissue relaxation through NO (Plotnick et al., 1997)

- It reduces platelet adhesion and aggregation (Mower & Steiner, 1982; Calzada et al., 1997). Its role is especially clear in human atheroma patients.

An imbalance between oxidant and antioxidant production has been shown in DCM dogs with heart failure (Freeman et al., 1999). As the cardiopathy develops, the animals increasingly produce quantities of oxidants (malondialdehyde is used as a marker for lipid peroxidation) and present lower levels of vitamin E (Freeman et al., 1999). Oxidative stress is thus said to play a role in the development of DCM. Similar observations were made within the framework of a recent study of dogs with heart failure secondary to degenerative valve disease or DCM.

In the light of the data obtained on humans and dogs, vitamin E supplementation is not expected to have any negative effects in cats with cardiac disease. In fact, such supplementation is expected to be beneficial, although this is yet to be confirmed as no studies have been conducted in this species. The optimal supplementation level depends on the quantity of unsaturated fatty acids in the food.

Vitamin C

Vitamin C is water-soluble. In addition to preventing oxidation of LDL lipoprotein, it is known to facilitate the regeneration of vitamin E. Studies on humans show that a single dose of vitamin C (2000 mg) or administration of 500 mg/day for four weeks promotes vasodilatation in coronary disease patients (Kugiyama et al., 1998). However, no specific data are available for cats and unlike humans, cats can synthetize vitamin C.

Copper

In cats deficient in copper and genetically sensitive to HCM, a high saturated fat content compared with omega-3 fatty acids (2:1) exacerbates the cardiac anomalies induced by copper deficiency (Jalili et al., 1995). This suggests that copper could be involved in HCM, although there is nothing to warrant changing the usual recommendations for copper (1.25 - 7 mg/1000 kcal in the cat). Furthermore, excess copper can act as a pro-oxidant.

Coenzyme Q10 (CoQ10)

Coenzyme Q10 (also known as ubiquinone) is an antioxidant that is naturally present in the mitochondria. It is found throughout the electron transport chain that produces energy, improving energy production by shunting defective elements from the respiratory chain (Rosenfeldt et al., 2002). Some studies on humans show its potential benefit in the event of cardiovascular pathology.

Flavonoids

Flavonoids are substances belonging to the family of plant-extracted polyphenols. Epidemiological studies on humans show an inverse relationship between the consumption of fruits and vegetables, which are rich in flavonoids, and cardiovascular risk (Steinmetz & Potter, 1996).

A very high number of in vivo and in vitro cardiovascular pathology studies show the benefit of consuming diverse sources of flavonoids: black and green tea (Duffy et al., 2001a,b; Geleijnse et al., 2002), grape juice (Keevil et al., 2000) and red wine (Rimm et al., 1996; Rein et al., 2000a).

Flavonoids have several modes of action. In addition to their antioxidant action, they have an antithrombotic action (Rein et al., 2000b) and, by increasing endothelial production of NO, a vasodilative action (Karim et al., 2000). Their beneficial role in cats with cardiac disease is yet to be determined.

Selenium

Selenium is an essential trace element that is an integral part of glutathione peroxidase, an antioxidant enzyme. It works in synergy with vitamin E. Selenium intake must be carefully dosed as tolerable minimum and maximum levels are fairly close to each other. An adequate intake of selenium goes hand in hand with the fulfillment of glutamate, cysteine and glycine requirements; these three compounds are necessary for glutathione synthesis.

Taurine

Besides its major role in cardiac inotropism, taurine also has an antioxidant action that protects the myocardium membrane.

Conclusion

The first dietary goal in the event of cardiac disease in cats is to combat the occurrence of cachexia, which can in turn contribute to the progression of the disease. This can be achieved in several ways: increasing level of dietary protein, increasing levels of omega-3 fatty acids and promoting food intake.

Taurine supplementation is necessary in the event of DCM (especially taurine-deficiency DCM). It is also indicated in the event of hypokalemia.

Low-sodium foods should be restricted to symptomatic animals (with signs of heart failure). When used too early in the stage of the disease, sodium restriction may induce undesired side-effects, such as stimulation of the renin-angiotensin-aldosterone system.

Unfortunately, no data is available concerning the benefits of long chain omega-3 fatty acids in the feline cardiac patient. Their antithrombotic and anti-arrhythmic roles as demonstrated in other species would be very beneficial in cats. The same can be said of antioxidants.