Article

Mortality in rheumatoid arthritis: Relationship to single and composite measures of disease activity

Staffordshire Rheumatology Centre, The Haywood, Stoke-on-Trent, UK.
Rheumatology (Impact Factor: 4.44). 05/2001; 40(4):447-52.
Source: PubMed

ABSTRACT Rheumatoid arthritis (RA) is a heterogeneous disease characterized by a variable course of remissions and relapses. Single measures of disease activity at only one point in time may not reflect the overall control of disease activity.
The aim was to determine (i) the predictive value of 20 baseline demographic and disease variables on mortality, and (ii) the relationship between serial measures of the Stoke index (SI; a validated index of disease activity in RA) and mortality in RA.
Mortality in 309 RA patients followed up for a median of 14 yr was analysed retrospectively. The standardized mortality ratio (SMR) was calculated for all causes of death. The predictive values of baseline and time-integrated variables were assessed using multivariate Cox proportional hazards regression analysis.
The SMR was 1.65. At baseline, only nodules, erosions, RA latex titre, white cell count and globulin level were predictive of mortality after correction for age, sex and disease duration. Using a stepwise Cox proportional hazards regression model, the most powerful predictors of mortality were age, nodules and RA latex titre. Individual measures of disease activity and the SI at baseline were not predictive of mortality. However, the mean level of the SI over 12 months was related to mortality (P=0.039).
At baseline, the demographic and disease variables most significantly related to mortality in RA are age, nodules and RA latex titre. Individual measures of disease activity at a single point in time are poor predictors of mortality in RA. However, measurement of the mean level of disease activity over time using the composite SI has a significant relationship with mortality. A high level of sustained inflammation appears to be an important predictor of premature death.

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    ABSTRACT: Rheumatoid arthritis (RA) patients have premature mortality. Contrary to the general population, mortality in RA has not declined over time. This study aimed to evaluate determinants of mortality in RA by examining causes of death (CoDs) over time, accuracy of CoD diagnoses, and contribution of RA medication to CoDs. This study further evaluated detection rate of reactive systemic amyloid A amyloidosis, which is an important contributor to RA mortality. CoDs were examined in 960 RA patients between 1971 and 1991 (Study population A) and in 369 RA patients autopsied from 1952 to 1991, with non-RA patients serving as the reference cases (Study population B). In Study population B, CoDs by the clinician before autopsy were compared to those by the pathologist at autopsy to study accuracy of CoD diagnoses. In Study population B, autopsy tissue samples were re-examined systematically for amyloidosis (90% of patients) and clinical data for RA patients was studied from 1973. RA patients died most frequently of cardiovascular diseases (CVDs), infections, and RA. RA deaths declined over time. Coronary deaths showed no major change in Study population A, but, in Study population B, coronary deaths in RA patients increased from 1952 to 1991, while non-RA cases had a decrease in coronary deaths starting in the 1970s. Between CoD diagnoses by the clinician and those by the pathologist, RA patients had lower agreement than non-RA cases regarding cardiovascular (Kappa reliability measure: 0.31 vs. 0.51) and coronary deaths (0.33 vs. 0.46). Use of disease modifying anti-rheumatic drugs was not associated with any CoD. In RA patients, re-examination of autopsy tissue samples doubled the prevalence of amyloid compared with the original autopsy: from 18% to 30%. In the amyloid-positive RA patients, amyloidosis was diagnosed before autopsy in only 37%; and they had higher inflammatory levels and longer duration of RA than amyloid-negative RA patients. Of the RA patients with amyloid, only half had renal failure or proteinuria during lifetime. In RA, most important determinants of mortality were CVDs, RA, and infections. In RA patients, RA deaths decreased over time, but this was not true for coronary deaths. Coronary death being less accurately diagnosed in RA may indicate that coronary heart disease (CHD) often goes unrecognized during lifetime. Thus, active search for CHD and its effective treatment is important to reduce cardiovascular mortality. Reactive amyloidosis may often go undetected. In RA patients with proteinuria or renal failure, as well as with active and long-lasting RA, a systematic search for amyloid is important to enable early diagnosis and early enhancement of therapy. This is essential to prevent clinical manifestations of amyloidosis such as renal failure, which has a poor prognosis. Nivelreuma aiheuttaa nivelmuutoksia, mutta se myös lyhentää elinikää. Reumapotilaat kuolevat samoihin sairauksiin kuin väestö, mutta myös nivelreumaan. Vaikeassa reumassa toisinaan kehittyvä sekundaarinen amyloidoosi on tärkeä elinikää lyhentävä tekijä. Reumapotilaiden elinikä ei ole pidentynyt toisin kuin väestön keskimääräinen elinikä. Tämän väitöskirjatutkimuksen tavoitteena oli selvittää reumapotilaiden lisääntyneeseen kuolleisuuteen vaikuttavia tekijöitä tutkimalla reumapotilaiden kuolinsyitä pitkän ajanjakson aikana, kuolinsyydiagnoosien tarkkuutta, reumalääkityksen vaikutusta kuolinsyihin ja sitä kuinka kattavasti amyloidoosi oli diagnosoitu. Väitöskirjatyössä tutkittiin 960 reumapotilaan kuolinsyyt vuosilta 1971 - 1991 (aineisto A) ja 369 reumapotilaan ja verrokkien kuolinsyyt, jotka oli todettu ruumiinavauksessa vuosina 1952 - 1991 (aineisto B). Kuolinsyydiagnoosin osuvuutta tutkittiin vertaamalla ruumiinavauslähetteen oletettuja kuolinsyitä ruumiinavauksessa todettuihin kuolinsyihin (aineisto B). Ruumiinavauksessa otetut kudosnäytteet tutkittiin uudelleen 90%:lta potilaista amyloidoosin toteamiseksi ja sairaskertomustiedot kerättiin vuoden 1972 jälkeen kuolleilta reumapotilailta (aineisto B). Sydän- ja verisuonitaudit, reuma ja infektiot olivat reumapotilaiden tärkeimmät kuolinsyyt. Reuman aiheuttamat kuolemat vähenivät. Reumapotilaiden sepelvaltimotautikuolemat lisääntyivät 1952 - 1991 välillä. Verrokeilla ne kääntyivät laskuun 1970-luvulla (aineisto B). Reumapotilaiden sydän- ja verisuonitauti- ja sepelvaltimotautikuolemat olivat alidiagnosoituja. Reumalääkkeiden käyttö ei vaikuttanut kuolinsyihin. Amyloidoosi oli todettu elinaikana vain kolmasosalla reumapotilaista. Reumapotilaiden kudosnäytteiden uudelleentutkiminen lisäsi amyloidoosin määrän kaksinkertaiseksi ruumiinavauksessa todettuihin verrattuna. Näillä potilailla tulehdusarvot olivat olleet korkeammat ja reuma oli kestänyt pidempään. Heistä vain puolella oli elinaikana todettu munuaisten vajaatoiminta tai valkuaisvirtsaisuus. Reumapotilaiden tavallisimpia kuolinsyitä olivat sydän- ja verisuonitaudit, reuma ja infektiot. Reumapotilaiden sepelvaltimotauti näyttää olevan alidiagnosoitu. Sepelvaltimotaudin aktiivinen etsiminen ja tehokas hoito ovat tärkeitä kuolleisuuden vähentämisessä. Amyloidoosi myös voi jäädä toteamatta elinaikana. Amyloidoosia kannattaa etsiä etenkin reumapotilailta, joilla on munuaisten vajaatoiminta, valkuaisvirtsaisuus tai pitkään kestänyt ja aktiivi reuma. Amyloidoosin varhainen toteaminen on tärkeää, jotta voidaan estää sen eteneminen reuman hoitoa tehostamalla.
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