Lack of Association Between Hypertension and Hypothyroidism in Postmenopausal Women Seen in a Primary Care Setting

Transcription

1 Lak of Assoiation Between Hypertension and Hypothyroidism in Postmenopausal Women Seen in a Primary Care Setting George R. Bergus, MD, Christina Randall, RN, PhD, and Randy Van Peursem Bakground: Several studies undertaken in hospital-based speialty linis have reported an assoiation between hypertension and hypothyroidism. This work examines the assoiation between these two ommon disorders in postmenopausal women seen within a primary are offie setting. Methods: Seven hundred seven postmenopausal women aged 50 years and older were studied using a ross-setional design. Data on thyroid status, hypertension and risk fators, and patient demographis were olleted from the offie medial reord. Results: Overall, 45.4 perent of the population studied had hypertension and 10.9 perent had hypothyroidism. Compared with normotensive women, hypertensive women were signifiantly older (66.4 years versus 63.0 years, P ) and had a higher body mass index (29.2 kg/m2 versus 26.2 kg/m2, P ). Hypertension was signifiantly assoiated with diabetes mellitus and the use ofnsaids (odds ratios [OKs] = 1.77 and 2.63, respetively). We did not find a signifiant assoiation between hypertension and hypothyroidism (OR 1.04,95 perent onfidene interval 0.64 to 1.76). Conlusions: In this population of postmenopausal women we did not find hypertension to be assoiated with hypothyroidism. (J Am Board Fam Prat 1997;10: ) Hypothyroidism has been desribed as a ause of hypertension in manyi-s but not a1l 6-8 medial textbooks. Several researhers have reported an assoiation between hypertension and hypothyroidism in linial settings, but these studies have been undertaken in speialty linis largely using referred patients. 9 - I4 A ommunity-based study, however, found no differenes in mean blood pressures or the prevalene of hypertension in hypothyroid and euthyroid women. IS Both hypothyroidism and hypertension are ommon, and their ourrene inreases with age. In the ommunity setting, overt hypothyroidism ours in 1.5 to 2.0 perent of women and 0.2 perent of men. I6 Sublinial hypothyroidism, defined as an elevated thyroid-stimulating hormone (TSH) (up to 10 U/L) but with a normal free thyroxine, is ommon among per- Submitted, revised, 6 September From the Department of Family Pratie, University ofiowa, Iowa City. Address reprint requests to George R. Bergus, MD, Department of Family Pratie, The University ofiowa, 2133 Steindler Bldg, Iowa City, IA This paper was presented at the 29th annual spring onferene of the Soiety of Teahers of Family Mediine, San Franiso, 29 April sons older than 60 years; it has been doumented in 5.9 perent of an unseleted population of ommunity-dwelling elderly personsi7 and 14.6 perent of elderly women in a primary are geriatris lini. 18 The prevalene of hypertension (defined as a blood pressure of 140/9.0 mmhg or greater) inreases from less than 30 perent for white women aged 35 to 44 years to more than 50 perent for white women aged 65 to 74 years. I9 Beause hypertension and hypothyroidism are both ommon, their oexistene in patients might not indiate an assoiation. A ausative assoiation would be linially important if subsequent studies showed that early reognition and treatment of hypothyroidism prevent hroni hypertension from developing. Prevention of hypertension ould prevent stroke and myoardial infartion. The purpose of our projet was to examine the assoiation between hypertension and hypothyroidism in postmenopausal women seen in a primary are offie setting. This group was seleted beause both diseases our widely in this population. We hypothesized that if an assoiation existed, then a diagnosis of hypothyroidism should our in a greater perentage of hyper- Hypertension, Hypothyroidism After Menopause 185

2 Table 1. Comparison of Hypertensive and Nonnotensive Women, by Patient Charateristis. Charateristis Hypertensive (n = 321) Normotensive (n = 386) PValue Patients (age distribution) 50 to 59 years 60 to 69 years 70 to 79 years 80 to 89 years 90 years and older Age, mean years (SD) Body mass index, mean kg/m 2 (SD) Median number of visits 2 years before index visit Median number of visits year after index visit (11.0) 29.2 (6.3) (10.4) 26.2 (5.2) tensive women than in that of their normoten SIve peers. Methods All postmenopausal women aged 50 years and older who were seen at the family pratie offie between 1989 and 1993 and who used this faility for their primary health are were eligible for this study. The offie is in a university ommunity in the Midwest and reords more than 20,000 visits per year. The offie was onsidered to be a woman's soure of primary health are if she reeived her preventive health are at this offie, as indiated by at least one ervial ytologi smear during the study period. During the study period it was the reommendation of this offie that all adult women, regardless of age and hysteretomy status, undergo routine ytologi sreening. Data were olleted by hart review using a ross-setional design. There was at least 1 year between the visit for preventive are and the hart review. Patient harts were reviewed by researh assistants using a standard data-olletion instrument. Data on hypertension, hypothyroidism, diabetes mellitus, smoking, nonsteroidal anti-inflammatory drug (NSAID) use, estrogen use, oronary artery disease, ongestive heart failure, and hroni renal failure, as well as height, weight, and number of offie visits 2 years before and 1 year after the index visit were extrated from the harts. A patient's index visit was the first visit during the study period at whih she underwent ervial ytologi sreening. Reliability was heked by having the researh assistants reextrat data from 80 randomly seleted harts initially reviewed by the other reviewer. Agreement was exellent, with kappas greater than 0.95 for both hypertension and hypothyroidism. Classifiation Criteria Patients were lassified as having hypothyroidism if either of the following was reorded in the hart: 1. Elevated TSH or low free thyroxine (both as defined by the laboratory performing the test) preeding the index visit or within 1 year following the index visit. 2. Thyroid replaement presribed by the index visit or within 1 year following the index visit. Patients were lassified as having hypertension if any of the following were reorded in the hart: 1. Elevated blood pressures in the offie, as defined by diastoli blood pressure greater than 90 mmhg, on at least 3 oasions within 1 year of the index offie visit. 2. Taking mediations for treatment of hypertension, as doumented by any mention in the hart of the patient having been presribed a diureti, ~-bloker, a-bloker, alium hannel bloker, or angiotensin-onverting enzyme inhibitor at the time of the index visit or within 1 year of that visit. Doumentation of these drugs did not satisfy this riterion if the mediation was presribed for another ondition, suh as migraine, idiopathi edema, ongestive heart failure, angina, or renal protetion in the fae of diabetes mellitus. 3. Any reord within the offie hart of the diagnosis of hypertension in a progress note, problem list, health summary questionnaire, hospital disharge note, or onsultant's note preeding the index visit. Data Analysis When the variables were dihotomous, we performed a univariate analysis using hi-square, and 186 JABFP May-June 1997 Vol. 10 No.3

3 Table 2. Comparison of Hypertensive and Nonnotensive Women, by Perentage with Study Variable. Variable Hypertensive (n = 321) Nonnotensive (n = 386) PValue Obesity (BMI ~ 30 kg/m2) Coronary artery disease Diabetes mellitus NSAIDuse Congestive heart failure Estrogen use Ever smoker Current smoker Hypothyroidism l ll.s BMI - body mass index, NSAID - nonsteroidal anti-inflammatory drug. when they were ontinuous, we used the Student t-test or Mann-\Vhitney U test. Statistial analyses were performed with the Solo, Version 4, statistial software.2o The level of signifiane was set at Multivariate analyses were undertaken using logisti regression with hypertension as the dependent variable and hypothyroidism as an independent variable. Independent variables found to be signifiant in the univariate analysis at the 0.10 level and additional variables of onern were inluded in the model. For ease of interpretation, age was entered into the model by deade and body mass index was entered into the model by inrements of 5 kg/mg2. Power analysis was performed with Solo Power Analysis,2l Results Seven hundred forty-two women, aged 50 years and older, obtained their primary health are at this offie during the study period. Of these women, 35 were exluded beause they were still menstruating or their harts ould not be loated, leaving 707 women in the study population. The mean age of the patients was 64.6 years (SD 10.8 years). Patients reeived are at the study site a median of 3 times during the 2 years before the index visit and 2 times during the year after the index visit. Three hundred twenty-one of the women (45.4 perent) had hypertension and 77 women had hypothyroidism (10.9 perent). Hypothyroidism was diagnosed by abnormal laboratory findings in 49.4 perent of ases and by the use of thyroid replaement in 50.6 perent of ases. Hypertensive women were signifiantly older than their normotensive peers and had a signifiantly higher mean body mass index. Hypertensive women were also more likely to have a history of ongestive heart failure, a history of oronary artery disease, a history of diabetes mellitus, and to be hroni users of NSAIDs. The perentages of women who were urrent smokers or taking estrogen were similar in both groups. These univariate analyses are shown in Tables 1 and 2. The relations between hypertension and age and body mass index of the patients are shown in Figures 1 and 2, respetively. The perentage of hypertensive women who also had hypothyroidism, 11.5 perent, was higher than the perentage found in the normotensive group, 10.4 perent, but this differene was not statistially signifiant (P = 0.62). The perentages of ases of hypothyroidism diagnosed by abnormal laboratory findings and by being on replaement therapy were similar in both groups of women (P = 0.74). No assoiation was found between the two onditions when hypothyroidism was defined solely by an elevated TSH or low free thyroxine (P = 0.925). More women in the normotensive group also had a TSH level greater than 10 UIL than did women in the hypertensive group (10 versus 4, P = 0.04). A logisti model was reated with hypertension as the dependent variable and NSAID use, body mass index, hypothyroidism, age, and diabetes mellitus as independent variables. In this analysis the assoiation between hypothyroidism and hypertension had an odds ratio of 1.04 (onfidene interval 0.63 to 1.73). Age, body mass index, NSAID use, and diabetes mellitus were signifiantly assoiated with hypertension; the odds ratios for these assoiations are shown in Table 3. Restriting the definition of hypothyroidism to either an elevated TSH or a low free thyroxine in the logisti model did not ause the assoiation Hypertension, Hypothyroidism After Menopause 187

4 0 'iii 1: a. > ;. ~.- ~ a Age in years Figure 1. The perentage of women who had hypertension diagnosed, by age in deades. between thyroid status and hypertension to beome statistially signifiant (P = 0.97). Disussion Hypertension and hypothyroidism are ommon in postmenopausal women, but our offie-based study did not detet an assoiation between these two onditions. This lak of assoiation ontrasts with other reports about patients studied in speialty linis. Bing et a1 9 reported a ase series of 6 hypothyroid patients with hypertension who beame normotensive after treatment with thyroid replaement. Streeten and olleagues lo studied 688 patients referred to a speialty lini for evaluation and treatment of hypertension. Twenty-five of the patients (3.6 perent) were found to have hypothyroidism. After thyroid replaement therapy was initiated, 32 perent of the hypothyroid group beame normotensive. Streeten et al ld also reported that of 40 patients who beame hypothyroid following treatment with radioiodine, 16 (40 perent) also developed hypertension, but after reeiving thyroid replaement, 9 of the 16 (56 perent) returned to a normotensive ondition. These studies laked ontrol groups, and it is possible that individual patients who beame normotensive after thyroid replaement would have beome normotensive without this intervention. Saito et alii also found this assoiation in a ross-setional study of 477 patients with hroni thyroiditis seen in a hospital-based thyroid lini. Less than 6 perent of the 308 euthyroid patients had hypertension ompared with 14.8 perent of the 169 patients with hypothyroidism. Mean blood pressures were higher, and hypertension was more ommon only in hypothyroid patients who were aged 50 years and older. In the analysis patients were stratified by age, but not by other fators known to be assoiated with hypertension, suh as body mass index, NSAID use, and diabetes mellitus. Response to thyroid replaement was reported for a subset of 18 patients. Although 13 (72 perent) of the treated patients had a deline in blood pressure after being presribed L-thyroxine, the authors aknowledged that the drop in blood pressure ould represent a plaebo response. 22 An additional problem ommon to most of the previous researh is that referred populations were used to study the assoiation between hypertension and hypothyroidism. The reported assoiation ould be due to seletion and referral bias and not apply to patients seen in a primary are setting. 23 Referral patterns influene the harateristis of patients with hypertension seen by physiians; therefore, studies undertaken in speialty linis do not always generalize to hypertensive patients seen in another setting. 24,25 Although we did not find an assoiation between hypertension and hypothyroidism, our methods orretly found fators that are well known to be related to hypertension. These inlude age,26 body mass index,26 NSAID use,27 and diabetes mellitus. 28 It is possible that our inability to find an assoiation between hypertension and hypothyroidism is due to impreision in the lassifiations of thyroid status. About one half of the women in this study with the diagnosis of hypothyroidism did not have their ondition onfirmed by laboratory studies. Additionally, some of the women with doumented elevation in TSH had, in fat, sublinial hypothyroidism (an elevated TSH less than 10 U/L and a normal free thyroxine). To assess mislassifiation bias, we started with a liberal definition of hypothyroidism (abnormal laboratory findings or being on tllyroid replaement) and then used a more restritive definition of hypotllyroidism in additional analyses. Regardless of our definition of hypothyroidism, we were unable to show a signifiant assoiation with hypertension. 188 JABFP May-June 1997 Vol. 10 No. 3

5 Our inability to find an assoiation between these two disorders is in agreement with the findings of a study by Endo et ai, 15 in whih 81 hypothyroid women were ompared with 73 euthyroid women drawn from the surrounding ommunity. No signifiant differenes in the mean blood pressures or in the prevalene ofhypertension were deteted after stratifying the patients by age. There are several weaknesses in our study design that should be addressed. A primary onern is that our data were not prospetively olleted but were obtained by retrospetive review of offie reords. This design is suseptible o 'iii t Q. >. to bias from a systemati underreporting of hypothyroidism in hypertensive women when ompared with their normotensive peers, whih would obsure a relation between the two onditions. Patients with hypertension, however, had more physiian visits before and after the index visits than did their normotensive peers. The inreased ontat with medial providers should have inreased the opportunities for deteting hypothyroidism, so that our data would be biased to show an assoiation between hypertension and hypothyroidism when one did not atually exist. We found a greater perentage of hypertensive women had TSH measurements in their harts than did their normotensive peers (43.9 perent versus 37.6 perent), although this differene did not reah statistial signifiane (P = 0.09). Beause of these findings we think it unlikely that mislassifiation resulting from a detetion bias is obsuring a relation between hypertension and hypothyroidism. It is also possible that some of the women with hypertension had their hypothyroidism diagnosed and treated at another medial are site. We attempted to avoid this problem by studying only a population of women who obtained their preventive health are at the primary are offie used for the study. Additionally, we reviewed all medial data available to us in the offie reord, inluding onsultations, offie notes, a self-administered health questionnaire, and hospital admission and disharge notes. It is likely that either a new or previous diagnosis of hypothyroidism at another site would have been unovered by the ~ ~ o < MI (kg/m2) ~ 40 Figure 2. The perentage of women who had hypertension diagnosed, by body mass index (BM!) in inrements of 5 kg/m2. primary are physiian during visits for preventive health are. Although our seletion riteria ould have biased our findings, as only 52 perent of all women aged 50 years and older obtained ervial ytologi sreening in our offie during the study period, the data on the prevalene of hypertension in the studied group are onsistent with that found in unseleted populations. 19 A third onern should fous on our sample size. It might be argued that we had an insuffiient number of patients to detet a linially signifiant assoiation between hypertension and hypothyroidism. With 707 patients and a 10.9 perent prevalene of hypothyroidism, however, we had a power of 0.8 for deteting an odds ratio of for the assoiation between hypothyroidism and hypertension by the logisti regression model. The odds ratio for the assoiation of these two onditions in the Saito et al study was J I Lastly, our findings pertain only to postmeno- Table 3. Logisti Modeling of the Assoiations Between Hypertension and Seleted Fators. Variable Odds Ratio (95 % ei) PValue BMI (in 5-kg/m ( ]) inrements) Age (in deades) 1.41 ( ) NSAIDuse ( ) Diabetes mellitus 2.63 ( ) Hypothyroidism 1.04 ( ) 0.87 CI - onfidene interval, EMI - body mass index, NSAID - nonsteroidal anti-inflammatory drug. Hypertension, Hypothyroidism After Menopause 189

6 pausal women. We speifially seleted this population beause they have the highest rates of hypothyroidism. It is possible that hypertension and hypothyroidism are assoiated in young women or in men. Our study annot ontrol for this possibility. It is also diffiult to be ertain that our findings are generalizable to postmenopausal women in other geographi regions. Speifi soiodemographis of the group studied are largely unavailable. We know that 76 perent of the patients lived in the ounty where the offie was loated and that the 1990 US Census data show 98.6 perent of women aged 50 years or older living in the ounty to be white. 29 The ounty also had a highly eduated population, with 69.3 perent of the population aged 25 years or older having eduation beyond high shool. 30 We also know that approximately 10 perent of the women aged 50 to 64 years who obtained ervial ytologi sreening at this offie were on Mediaid or Mediare or were uninsured. At a minimum, our findings should apply to other groups of highly eduated white women. In summary, we investigated the assoiation of hypertension and hypothyroidism in postmenopausal women reeiving their health are in a family pratie offie setting. Although we found hypertension and hypothyroidism to be ommon in this population, we did not find evidene that these two onditions were diretly assoiated. Instead, we found hypertension to be related to age, body mass index, NSAID use, and diabetes mellitus. Our findings differ from those of previous reports, but the setting in whih we olleted our data differed from those in most of the earlier reports. Our study raises questions about whether reports linking hypertension and hypothyroidism in referred populations an be generalized to postmenopausal women seen in a primary are setting. Referenes 1. Hall WD, Wollman GL, Tuttle EP Jr. Diagnosti evaluation of the patient with systemi arterial hypertension. In: Shlant RC, Alexander RW, editors. The heart. Companion handbook. 8th ed. New York: MGraw-Hill, 1994: Frohlih ED. Pathophysiology of systemi arterial hypertension. In: Shlant RC, Alexander RW, editors. The heart. Companion handbook. 8th ed. New York: MGraw-Hill, 1994: Williams GH. Hypertensive vasular disease. In: Isselbaher KJ, Braunwald E, WilsonJD, MartinJB, Faui AS, Kasper DL, editors. Harrison's priniples of internal mediine. 13th ed. New York: MGraw Hill, 1994: Kaplan NM. Endorine hypertension. In: Wilson JD, Foster DW, editors. Williams textbook of endorinology. 8th ed. Philadelphia: WB Saunders, 1992: Goldszer RC, Solomon HS. Hypertension. In Branh WT Jr, editor. Offie pratie of mediine. 3rd ed. Philadelphia: WB Saunders, 1994: Grossman A, editor. Clinial endorinology. Oxford: Blakwell Sientifi Publiations, WyngaardenJB, Smith LH, BennetJC, editors. Ceil textbook of mediine. 19th ed. Philadelphia: WB Saunders, Dale DC, Federman DD, editors. Sientifi Amerian mediine. New York: Sientifi Amerian, Bing RF, Briggs RS, Burden AC, Russell GI, Swales JD, Thurston H. Reversible hypertension and hypothyroidism. Clin Endorinol Oxf 1980;13: Streeten DH, Anderson GHJr, Howland T, Chiang R, Smulyn H. Effets of thyroid funtion on blood pressure. Reognition of hypothyroid hypertension. Hypertension 1988;11: Saito I, Ito K, Saruta T. Hypothyroidism as a ause of hypertension. Hypertension 1983;5: Thompson WO, Dikie LFN, Morris AE, Hilkevith BH. The high inidene of hypertension in toxi goiter and in myxedema. Endorinology 1931; 15: Fuller H Jr, Spittell JA Jr, MConahey WM, Shirger A. Myxedema and hypertension. Postgrad Med 1966;40: Menof P. The thyroid and atherosleroti arterial disease. S Afr MedJ 1973;47: Endo T, Komiya I, Tsukui T, Yamada T, Izumiyama T, Nagata H, et al. Re-evaluation of a possible high inidene of hypertension in hypothyroid patients. Am HeartJ 1979;98: Tunbridge WM, Evered DC, Hall R, Appleton D, Brewis M, Clark F, et al. The spetrum of thyroid disease in a ommunity: the Whikham survey. Clin Endorinol Oxf 1977; 7 : Sawin CT, Castelli WP, Hershman JM, MNamara P, Baharah P. The aging thyroid. Thyroid defiieny in the Framingham study. Arh Intern Med 1985;145: Bemben DA, Winn P, Hamm RM, Morgan L, Davis A, Barton E. Thyroid disease in the elderly. Part 1. Prevalene of undiagnosed hypothyroidism. J F am Prat 1994;38: Drizd T, Dannenberg A, Engel A. Blood pressure levels in persons years of age in and trends in blood pressure from 1960 to 1980 in the United States. Vital Health Statistis, series 11: data 190 JABFP May-June 1997 Vol. 10 No. 3

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