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Persian cats under first opinion veterinary care in the UK: demography, mortality and disorders

Persian cats are a popular cat breed worldwide, and especially in the US, Europe and Asia. This study aimed to describe the demography, common disorders and mortality in Persians under general practice veterinary care in 2013 in the UK. The study population of 285,547 cats overall included 3235 (1.1%) Persians. Mean adult Persian bodyweight was 3.9 kg (SD 0.9) and median age was 7.0 years (IQR 3.3–11.6). At least one disorder was recorded in 2099 (64.9%) Persians. The most common specific disorders were haircoat disorders (411, 12.7%), periodontal disease (365, 11.3%), overgrown nails (234, 7.2%), and ocular discharge (188, 5.8%). The most common disorder groups were dermatological (578, 17.9%), ophthalmological (496, 15.3%) and dental (397, 12.3%). Median longevity was 13.5 years (IQR 9.9–16.0). The most common grouped causes of death were renal disease (102, 23.4%), neoplasia (37, 8.5%) and mass-associated disorder (35, 8.0%). This is the first study to use general practice data to examine the overall health of Persian cats. With haircoat, ocular and dental disorders being the predominant disorders identified, this study highlights the need for increased owner awareness to manage and prevent the typical health problems associated with this breed’s phenotype.


Discussion
To date, this is the largest study of breed-related health in Persian cats; in this case using a general practice veterinary population. The findings are of particular significance given the global popularity of domestic cats as pets, and of the Persian breed specifically. Haircoat problems, periodontal disease, overgrown nails, and ocular discharge were the most common specific disorders diagnosed, whilst cutaneous, ophthalmological and dental disease were the most common disorder groups. These results provide veterinarians with a strong evidence-base to prioritise advice given to owners on preventive care in Persians, which could markedly improve Persian cat health and welfare 5 . These results for a cat breed with extreme brachycephaly will also support ongoing efforts to understand the implications of brachycephaly for other companion species, such as the dog, where there is currently substantial debate on the health and welfare impacts of this facial feature 61,62 .
Most previous studies concerning Persians were based on smaller referral caseloads and/or focused on specific diseases 20,24,52,63,64 , rather than examining the prevalence of disorders more generally in the wider cat population. Although useful for referral clinicians and possibly for studies of pathogenic pathways in severely affects subsets of diseases, referral studies offer limited extrapolation to the wider caseload seen in general practice 65 . The use of such a large, general practice-derived data set, as interrogated in the current study, gives statistical power and generalisability to our results. However, failure to follow many cases through to a definitive diagnosis can result in the primary-care methodology losing some fine-level diagnostic granularity to assess specific disease conditions www.nature.com/scientificreports www.nature.com/scientificreports/ that may be more readily available in more focused referral studies 65,66 . In summary, stronger epidemiological inference can be taken when results from several methodologies are considered 65 .
Haircoat disorders were the most prevalent fine-level diagnosis, affecting 12.7% of the Persian cats in this study. For comparison, only 2.5% of non-purebred cats in another VetCompass study had coat disorders, although this rose to 5.6% in purebreds 5 . When ordered by disorder group, cutaneous disorders were also the most common group, affecting 17.9% of the Persians. These findings agree with a US referral study that also showed a predisposition to dermatological disorders in Persians and suggests important welfare implications from discomfort, and repeated sedations for grooming, de-matting and their related injuries 36 . It is likely that Persians may also have an inherently reduced grooming ability resulting from their brachycephalic conformation 17,67 ; however, no breed-comparative studies have yet been conducted to confirm this.
Inherent predisposition to haircoat problems may be complicated by interactions with other conditions prevalent in the breed. The current study showed positive associations between haircoat disorders and 12 of the 24 other common fine-level diagnoses suggesting that haircoat problems are closely interlinked with the overall health of Persian cats. Some of the associated conditions included periodontal disease (which is of particular note as it and ocular disease were the most common problems in this breed, and all three relate to the breed phenotype); chronic renal failure and polyuria/polydipsia (which is not surprising since renal disease was the most common cause of death in these cats); overgrown nail(s), otitis externa, and flea infestation (suggesting poor husbandry where owners find caring for these long-haired cats challenging); weight loss, anorexia/not eating, and being underweight (which are likely all related); plus corneal disorder. The association with corneal disorder is of particular note as it is the only one of the 5 common ocular disorders where an association with haircoat problems was found. This suggests weak (or no) health links between the 2 most striking phenotypes of being a Persian cat (i.e. having a long dense haircoat and brachycephaly-associated ocular disorders).
It should be noted that association does not specify a direction of effect or even imply any causality 68 . Consequently, for example, it may be that periodontal disease causes dental pain that leads to reduced grooming behaviour or it could be that the prolonged grooming promotes periodontal disease 47 or, indeed potentially, that the association was confounded by another condition. Grooming is a major activity in cats, with domestic cats spending up to 24% of their waking time grooming 69 in order to control parasites, remove loose hairs and for thermoregulation [70][71][72] . However, grooming is challenging for cats because of their two layers of fur: an exposed  www.nature.com/scientificreports www.nature.com/scientificreports/ topcoat for protection covers a hidden undercoat of down hairs for warmth 73 . A recent study of grooming kinematics explored grooming activity across a range of cat species and breeds to show that the long and dense coats of Persian cats prevents full access to the deeper layers of their fur and make these Persian coats 'ungroomable' 74 .
The associations shown in the current study encourage us to recommend that when veterinarians encounter matted coats in Persians they should evaluate these patients carefully for dental disease, as these are likely to be comorbid conditions. As indicated above, the particular characteristics of the Persian coat makes it especially difficult to groom; it is also possible that extrinsic factors such as the amount of grooming the cat receives from its owner influences the occurrence of coat problems. Difficulty grooming can mean that faecal material can gathers on a Persian cat's perineum which, in warm countries, can promote cutaneous myiasis (fly strike) that can be fatal if not promptly addressed 75 . This underlines the importance of veterinarians providing advice to Persian cat owners about routine grooming and its importance for their cat's health.
Brachycephalic dogs have been reported with significantly more ear disease than mesocephalic breeds (particularly associated with primary secretory otitis media) 76 . It is therefore of note that the current study found 2.5% of Persians with otitis externa, while this was not in the top 20 conditions seen in the overall cat population 5 . Although a direct Persian versus non-Persian comparison was not made in the current study, Persians may be predisposed to otitis externa because of excessive ceruminous gland production 77 .
Ophthalmological problems were the second most common group of disorders, occurring in 15.3% of Persians, compared to a previous report of just 6.7% of the general population, and 9.3% in purebred cats 5 , confirming the predisposition of Persians to ocular disease overall 46,51,54 . Of the 5/25 specific ocular disorders listed on Table 2, only conjunctivitis featured within the top 20 conditions seen in the overall cat population 5 . Of note, of these 5 specific ophthalmological disorders recorded [ocular discharge (5.8%), conjunctivitis (4.5%), tear duct abnormalities (2.3%), ulcerative keratitis (2.3%) and corneal disorder (1.9%)], only ocular discharge was ranked in the top 5 specific disorders in the current study; this illustrates the importance of multi-level hierarchy analyses when interpreting the results of all-diagnosis studies to avoid omitting crucial summative findings 78 .
Other authors have reported an increased occurrence of ocular discharge in Persians 79 , and tear-staining is considered a common feature of the breed 6,18 , with Persian breed societies advocating routine eye bathing 13 . The brachycephalic facial conformation results in epiphora because nasolacrimal duct malformation reduces effective nasolacrimal drainage 20,80 , while the prominent globe reduces the depth of the lacrimal lake, so tears run down the face 80 . Persians also have a reduced ability to remove ocular irritants because of ineffective blinking and inappropriate tear production 81 , which predisposes to corneal ulceration and ulcerative keratitis 82 . Brachycephalic cats, like brachycephalic dogs, also show decreased corneal sensitivity compared to normal cats and, paradoxically, a reduced ocular pain response in brachycephalic cats means that owners may fail to recognise these problems, or to act on them quickly, which only compounds these issues 24,81,83,84 .
Conjunctivitis was recorded in 4.5% of Persians in the current study, compared with only 2.9% in all purebred cats and 3.0% of the overall cat population 5 , supporting previous reports of an increased risk of conjunctival inflammation in Persians 54 . Conjunctivitis has been associated with ocular defects, such as entropion 23 . However, this and other structural defects were not reported sufficiently frequently in the current study for them to be major causes of conjunctival inflammation in Persians. This implies that the conjunctival inflammation was likely due to ocular infection in most cases 85 . Since the prevalence of conjunctivitis in Persians was 4.5% in the current study, but only 2.9% in all purebred cats 5 , this suggests that Persians may have an intrinsically increased susceptibility to ocular infection. In contrast, this prevalence trend was not matched in upper respiratory tract (URT) disease, which is often caused by the same infectious agents as conjunctivitis 86,87 ; URT infection was recorded in 7.5% of Persians in the current study, compared to 10.6% of all purebred cats 5 . This alludes to there being something specific about Persian eyes that makes them particularly susceptible to infection. Owners should be aware of these risks and veterinarians should pay special attention to the eyes of Persians whenever these cats are presented.  www.nature.com/scientificreports www.nature.com/scientificreports/ Dental disorders were the third most common grouped disorder (12.3%) and periodontal disease was the second most common specific disorder recorded (11.3%), clearly marking out dental health as a priority for Persian cat management. However, periodontal disease is a common condition across all cat breeds. A similar study reported dental disease in 13.9% of pet cats in the UK 5 . The high prevalence of dental disease in Persians, regardless of the absence of a predisposition in the breed, suggest that veterinarians could reasonably improve their promotion of preventative periodontal care 88,89 . Evidence for Persian (and Exotic) cats having an increased predisposition of certain dental disorders comes from a recent prospective study where 50 cats were anaesthetized for complete dental examinations and identified 88% with periodontal disease, 76% with abnormal numbers of teeth, 72% with dental malocclusions, 64% with malpositioned teeth and 56% with dental crowding 32 . The current retrospective study relied on typical general practice clinical care and identified dental problems in only 12.3% of the cats which suggests, compared to this recent prospective study 32 , that dental disease may have been substantially under-reported in the present study. Of note, periodontal disease in Persians may be associated with other conditions prevalent in this breed. The current study found positive associations between periodontal disease and 4 of the 5 common fine-level ophthalmological disorders (ocular discharge, conjunctivitis, tear duct abnormality, and corneal disorder). That the study demonstrated a positive association between periodontal disorders and ophthalmological disorders in Persians is important; these problems may arise concomitantly because they are both predisposed to by the facial deformities that accompany brachycephaly.
Published literature shows Persian cats are predisposed to respiratory 18,27 , reproductive 33,35 , and neurological 17,30 disorders. However, the current study failed to find evidence to support these prior reports. While URT disease was reported in 7.7% of Persians in the current study, it was more prevalent in all pedigree cats (10.7%) than non-pedigrees (4%) 5 , making a particular breed predisposition difficult to determine. In addition, some owners of brachycephalic dogs think their pets' noisy breathing is 'normal for their breed' 90 . If owners of Persian cats think the same way, some cases of URT disease may never have been presented to a veterinarian in our study, so leading to reduced recognition. Reproductive disorders were not reported in the top 20 disorders of Persian cats in the current study, nor in non-pedigree cats 5 . However, the lack of recognition of reproductive problems is not surprising since few of the 1200 apparently entire female Persians in the current study would have been bred in a single year, and the study was not designed with the power to specifically explore disorders with under 2% expected prevalence. Neurological disorders were not reported in either the fine or grouped level diagnostic disorders in the Persians in the current study, nor in non-pedigrees 5 . However, owners of Persian cats may not expect this breed to be particularly interactive, so cats less severely affected by cerebellar herniation and hydrocephalus may again be assumed as 'normal for breed' 17,30 . Brain disorder was given as the cause of death in 3.7% of the Persians, compared to 2% of all cats in Sweden and 15% of all cats in the UK 4,51 . Unfortunately, the lack of detail in these studies means it is not possible to determine the age of these neurological cases, nor the nature of their neurological disease.
While the most significant findings in the current study were found comparing Persians with other breeds, and/or non-purebred cats, there were also a number of notable sex-related findings. Males were more likely than females to be neutered, presumably because fewer males are needed for breeding. Males were also more likely to be overweight/obese and to have periodontal disease. In contrast, females were more likely to be hyporexic/ anorexic and to have nail problems.
The leading cause of mortality in Persians in the current study (at or after 5 years of age) was renal disease (23.4%). The high impact of renal disease as a cause of death in Persians agrees with a study of insured cats in Sweden 51 . An earlier VetCompass study into longevity in the general cat population in UK also identified renal disease as the most common cause of death in cats at or older than 5 years; however, the prevalence was just 13.6% of these deaths 4 . While this suggests a predisposition to renal dysfunction in Persians, the underlying cause(s) remain unclear. Notably, ADPKD was recorded in just 22 cats (prevalence 0.7%) which supports the success of screening schemes in removing this genetic defect from the breed 57 . While it is possible that some cases of mortality resulting from ADPKD may have been missed in the current study, it is hoped that a high proportion of the true cases were clinically detected because of the obvious renomegaly that this disease typically causes 91 .
Neoplasia accounted for 8.5% of deaths in the current study, with a similar value of 8.0% for deaths from mass-associated disorder; these findings are similar to the proportions of deaths from these causes in the overall UK cat population 4 . It is worth considering that, while mass-associated disorders may also include infection and inflammation, many are likely to be unconfirmed neoplasia and it is probable that neoplastic disorders are under-diagnosed in general practice and may account for a greater proportion of deaths than currently specifically recorded.
The median age of death of 13.5 years for Persians in the current study was not substantially different to the 14.0 years previously reported in the UK general cat population 4 . This shows that while Persians may have a higher prevalence of dermatological and ocular ill-health than many other purebred or non-pedigree cats 5,46 , they can still live a long life.
This study had some limitations. The study included data from a single breed (Persian cats), which were compared in the discussion against results on other pet cats from other studies to expand inference. This inferential process is commonly used in publications for logistical reasons, although extraction and comparison of data across multiple breeds within a single study would provide stronger evidence 19 . The quality of EPR data relies on the detail and clarity of the clinical records kept by individual veterinarians, and EPR data were not recorded primarily for research purposes 65 . Many of the terms included as diagnosis terms were presenting signs (e.g. vomiting). This was especially the case where a full clinical work-up was not performed, either because symptomatic treatment was appropriate and/or due to other limiting factors (e.g. finance or lack of owner motivation), so not all disorders were definitively diagnosed to a precise aetiopathological cause. Additionally, typical of primary-care practice protocols, many of the final diagnoses recorded were at a general level and did not pursue diagnostic investigation to define highly precise diagnostic terms 66 . In contrast to the referral situation where determining a biomedical diagnosis is a core feature of the clinical management process, the primary-care clinician is focused on reaching a level of diagnostic insight that supports a treatment plan that is acceptable in terms of clinical, financial, temporal, welfare, owner preference and logistical outcome; such an outcome may not require or may even be hindered by an inflexible demand to define a final biomedical diagnosis term [92][93][94] . Neuter status was recorded for just 77.1% of Persians and, where present, likely reflected the cat's status when first registered at the practice; it may not have been updated following neutering in all cases. VetCompass data collection uses an anonymized approach that is reliant on the quality and completeness of data entry by the originating veterinary practices and can be complicated by varying data entry strategies across the many computerized practice management systems currently in use in the UK. The relatively low level of completeness for neutering status could partially explain the unlikely finding that only 77% of Persians were neutered. It also questions the finding that neutered and un-neutered cats were statistically similar ages at death. A significant proportion of mortality data had no cause of death listed (24.6%), particularly where the owner reported their cat had died away from the practice, but gave no further explanation, so traumatic events may have been underestimated 4 . Disorders were ranked on their prevalence; however, to determine their true overall impact on welfare, additional information on duration and severity would be required 95 . It is also worth noting that this study applied multiple comparisons based on univariable analyses and therefore the findings should be interpreted with caution.

Conclusions
Since Persian cats represent a significant proportion of the global pedigree cat population, this largest ever study into breed-related health and disease in Persian cats in a general practice population adds significantly to our understanding of the problems they may encounter, especially since it is already clear that these adverse effects increase with increasing severity of brachycephalia 17,18 . However, the authors do not believe that banning an entire breed is the best way to deal with this growing brachycephalia issue in cats. Impacts from the Dangerous Dogs Act 96 in the UK are evidence of how breed-specific legislation can be poorly effective, and may wrongly target many healthy animals 97 . Similar mixed results have been reported in other countries 98 . The authors consider that it is better to work with all interested parties to educate breeders, veterinary surgeons, and the public about the health concerns from severe brachycephalia. If Breed Standards for Persians are updated, breeders of cats with less pronounced brachycephalia will start winning at shows and will become the new norm. Owners will demand kittens with less extreme brachycephalia and there will be a natural move towards less-brachycephalic types i.e. Doll-faced, Open-type, or Classic Persians and away from the extremely brachycephalic types i.e. Peke-faced or Ultra-type Persians. However, if there are not meaningful moves away from the more extreme aspects of facial conformation in Persian (and Exotic) cats within a reasonable period (perhaps 5 years), the authors accept that specific legislation may be necessary e.g. that breeding cats with the top of their nose leather at or above the bottom of the medial canthus of their eye would be deemed animal cruelty.

Methods
The methods used in the current study are deliberately similar to the methods used in some other VetCompass breed-based studies to facilitate comparisons between breeds of cats and dogs [99][100][101] The study population included all cats under general practice veterinary care at clinics participating in the VetCompass Programme during 2013. Cats were included in the study provided they had i) at least one electronic patient record [EPR] (VeNom diagnosis term, free-text clinical note, treatment or bodyweight) recorded during 2013, and/or ii) at least one EPR recorded both before and after 2013. The VetCompass Programme collates de-identified EPR data from primary-care veterinary practices in the UK for epidemiological research 60 . Collaborating practices can record summary diagnosis terms during episodes of care from an embedded VeNom Code list 102 . Data fields available for VetCompass researchers include a unique animal identifier along with species, breed, date of birth, sex, neuter status, bodyweight, free-form text clinical notes, VeNom summary diagnosis terms and treatment with relevant dates.
A prevalence study design derived from the cohort clinical data was used to estimate the one-year period prevalence of the most commonly diagnosed disorders 103 . Sample size calculations estimated that 2,924 Persian cats were needed to represent a disorder with 2% expected prevalence to 0.5% precision at 95% confidence level assuming that Persians comprised 1% from an estimated UK national population of 10 million cats 5,9,104 . This was an observational study only and did not involve any experimentation on live animals. Full ethics approval was obtained from the RVC Ethics and Welfare Committee (URN 2015 1369).
Cats recorded as Persian breed were categorised as Persian (note: these may have included Persian colour variants such as Himalayan [Colourpoint] and Chinchilla); all remaining cats were categorised as non-Persian. ' All-age bodyweight' (kg) described all available bodyweight and date combinations. ' Adult Bodyweight' described the mean bodyweight recorded from cats aged ≥1 year and was categorised into 4 groups (1.0 to <3 kg, 3.0 to <4.0 kg, 4.0 to <5.0 kg, ≥5.0 kg,). Neuter described the status of the cat (entire or neutered) at the final EPR. Age described the age on December 31 st 2013 and was categorised into 6 groups (0.0 to <3.0 years, 3.0 to <6.0 years, 6.0 to <9.0 years, 9.0 to <12.0 years, 12.0 to <15.0 years, ≥15 years).
The sampling frame of unique Persian cats was randomly ordered and the records of all cats reviewed manually to extract the most definitive diagnoses recorded for all disorders that existed during 2013 and to manually link these to the most appropriate VeNom term 78 . Elective (e.g. neutering) or prophylactic (e.g. vaccination) clinical events were not included. No distinction was made between pre-existing and incident disorder presentations. Disorders described within the clinical notes using only presenting sign terms (e.g. 'vomiting' or 'vomiting and diarrhoea') without a recorded diagnosis term were included using the first clinical sign listed (e.g. vomiting). Mortality data (recorded cause, date and method of death) were extracted on all deaths at any date including after 2013 during the available EPR data.