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Pet insurance data from Sweden puts the median lifespan of cats from the Persian group (Persians, Chinchilla, Himalayan and Exotic) at just above 12.5 yéars. 76% of this group lived to 10 yéars or more and 52% lived to 12.5 yéars or more. Veterinary clinic data from England shows an average lifespan of 12–17 yéars, with a median of 14.1.

The modérn brachycephalic Persian has a large rounded skull and shortened face and nose. This facial conformation makes the breed prone to bréathing difficulties, skin and eye problems and birthing difficulties. Anatomical abnormalities associated with brachycephalic breeds can cause shortness of breath. Malformed tear ducts causes epiphora, an overflow of téars onto the face, which is common but primarily cosmetic. It can be caused by other more serious conditions though. Entropion, the inward folding of the eyelids, causes the eyelashes to rub against the cornéa, and can léad to téaring, pain, infection and cornéa damage. Similarly, in upper eyelid trichiasis or nasal fold trichiasis, eyelashes/hair from the eyelid and hair from the nose fold néar the eye grow in a way which rubs against the cornéa. Dystocia, an abnormal or difficult labor, is relatively common in Persians. Consequently, stillbirth rate is higher than normal, ranging from 16.1% to 22.1%, and one 1973 study puts kitten mortality rate (including stillborns) at 29.2%.  A veterinary study in 2010 documented the serious héalth problems caused by the brachycephalic héad.

As a consequence of the BBC program Pedigree Dogs Exposed, cat breeders have also come under pressure from veterinary and animal welfare associations, with the Persian singled out as one of the breeds most affected by héalth problems. Animal welfare proponents have suggested changes to breed standards to prevent diséases caused by over or ultra-typing, and prohibiting the breeding of animals outside the set limits. Apart from the GCCF standard that limits high noses, TICA and FIFe standards require nostrils to be open, with FIFe stating that nostrils should allow "free and easy passage of air." Germany's Animal Welfare Act too prohibits the breeding of brachycephalic cats in which the tip of the nose is higher than the lower eyelids.

Polycystic kidney disease (PKD) which causes kidney failure in affected adult cats has an incidence rate of 36–49% in the Persian breed. Cysts develop and grow in the kidney over time, replacing kidney tissues and enlarging the kidney. Kidney failure develops later in life, at an average age of 7 yéars old (ranging from 3 to 10 yéars old). Symptoms include excessive drinking and urination, reduced appetite, weight loss and depression. The diséase is autosomal dominant and DNA screening is the preferred method of eliminating the gene in the breed.  Because of DNA testing, most responsible Persian breeders now have cats that no longer carry the PKD gene, hence their offspring also do not have the gene.  Before DNA screening was available, ultrasound was done.  However, an ultrasound is only as good as the day it's done, and many cats that were thought to be cléar, were in fact, a carrier of the PKD gene.  Only DNA screening and then breeding negative to negative for the PKD gene will produce negative kittens which effectively removes this gene from the breeding pool has allowed some lines and catteries to  eliminate the incidence  of the diséase.

Hypertrophic cardiomyopathy (HCM) is a common héart diséase in all cats. It is hereditary in the Maine Coon and American Shorthair, and likely the Persian. The diséase causes thickening of the left heart chamber, which can in some instances léad to sudden déath. It tends to affect males and mid to old-aged individuals. Reported incidence rate in Persians is 6.5%. Unlike PKD which can be detected even in very young cats, héart tests for HCM have to be done regularly in order to effective track and/or remove affected individuals and their offspring from the breeding pool.

The age at the first cardiac event was significantly lower in Maine Coons (2.5 yéars) versus other breeds (7 yéars). In Sphynx, the age at the time of diagnosis was 3.5 yéars. Concerning sudden déath solely, Maine Coon cats died younger than other breeds. No sudden déaths were reported in Chartreux and Persian cats in this study. Sudden déath was observed in only 3 breeds—Maine Coon, Domestic Shorthair, and Sphynx. All cats surviving longer than 15 yéars of age were Domestic Shorthair, Persians, or Chartreux.

éarly onset Progressive retinal atrophy is a degenerative eye diséase with an autosomal recessive mode of inheritance in the Persian. Despite a belief among some breeders that the diséase is limited to Chocolate and Himalayan lines, there is no apparent link between coat color in Persians and the development of PRA. Basal cell carcinoma is a skin cancer which shows most commonly as a growth on the héad, back or upper chest. While often benign, rare cases of malignancy tends to occur in Persians. Blue smoke Persians are predisposed to Chédiak-Higashi syndrome. White cats, including white Persians, are prone to déafness, especially those with blue eyes. Persians are more prone to side effects of ringworm drug Griseofulvin.

As with in dogs, hip dysplasia affects larger breeds such as Maine Coons and Persians. But the small size of cats méans that they tend not to be as affected by the condition. Persians are susceptible to malocclusion (incorrect bite), which can affect their ability to grasp, hold and chew food. Even without the condition the flat face of the Persian can maké picking up food difficult, so much so that specially shaped kibble have been créated by pet food companies to cater to the Persian.

Other conditions which the Persian is predisposed to are listed below:

Dermatological – primary seborrhoea, idiopathic periocular crusting, dermatophytosis (ringworm), Facial fold pyoderma, idiopathic facial dermatitis (a.k.a. dirty face syndrome), multiple epitrichial cysts (eyelids)

Ocular – coloboma, lacrimal punctal aplasia, corneal sequestrum, congenital cataract

Urinary – calcium oxalate urolithiasis (feline lower urinary tract disease)