Risk factor clustering in patients with hypertension and non-insulin-dependent diabetes mellitus. The Skaraborg Hypertension Project

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1 Journal of Internal Medicine 1998; 243: Risk factor clustering in patients with hypertension and non-insulin-dependent diabetes mellitus. The Skaraborg Hypertension Project E. BØG-HANSEN a,b, U. LINDBLAD b,c, K. BENGTSSON a,b, J. RANSTAM d, A. MELANDER d & L. RÅSTAM b,e From the a Skara Health Care Center, Skara; the b Department of Community Medicine, Malmö University Hospital, Malmö; c Skaraborg Institute, Skövde; d The NEPI Foundation, Malmö and Stockholm; and e National Public Health Institute, Stockholm, Sweden Abstract. Bøg-Hansen E, Lindblad U, Bengtsson K, Ranstam J, Melander A, Råstam L (Skara Health Care Center, Skara; Malmö University Hospital, Malmö; Skaraborg Institute, Skövde; The NEPI Foundation, Malmö and Stockholm; and National Public Health Institute, Stockholm; Sweden). Risk factor clustering in patients with hypertension and non-insulindependent diabetes mellitus. The Skaraborg Hypertension Project. J Intern Med, 1998; 243: Objectives. To assess the coexistence of hypertension and diabetes, associations with cardiovascular risk factors and the achievement of current treatment goals. Design. A community-based, cross-sectional, observational study. Setting. Hypertension and diabetes outpatient clinics in primary health care, Skara, Sweden. Subjects. All patients (n 1116; 488 men, 628 women) who performed an annual follow-up from May 1992 to September Main outcome measures. Hypertension, non-insulindependent diabetes mellitus (NIDDM), blood pressure, fasting B-glucose, lipids, HbAlc, body mass index (BMI), waist hip ratio (WHR). Results. Hypertension alone was found in 286 men and 430 women, hypertension and NIDDM combined in 102 men and 102 women, and NIDDM alone in 100 men and 96 women. Taking new cases into account, the proportion of hypertension among NIDDM patients was 57%, and the proportion of NIDDM among hypertensives was 26%. Men and women with both hypertension and NIDDM had a higher systolic blood pressure and women also had a higher diastolic blood pressure (men 168/88 mmhg, women 165/86 mmhg) than those with hypertension alone (men 152/87 mmhg, women 156/82 mmhg) (P 0.001). Cardiovascular risk factors accumulated in patients with both hypertension and NIDDM (triglycerides, BMI and WHR). A diastolic blood pressure 90 mmhg was achieved by 71% men and 84% women with hypertension. HbAlc 7.5% was attained by 71% men and 70% women with NIDDM. Conclusions. A considerable coexistence of hypertension and NIDDM was demonstrated. Cardiovascular risk factors clustered in patients with both diseases and their blood pressure was less controlled. These patients thus comprised a clinically defined group at high risk. By current guidelines, control of hypertension and NIDDM seemed appropriate. Keywords: clustering, hypertension, NIDDM, primary health care, risk factors, treatment goals. Introduction Both hypertension and non-insulin-dependent diabetes mellitus (NIDDM) are associated with increased cardiovascular morbidity and mortality, as well as with microvascular complications. Treatment of hypertension has been shown to reduce the risk of stroke [1 3], while its effect on ischaemic heart disease is dubious [4 5]. In both NIDDM and insulindependent diabetes mellitus (IDDM), treatment and improved control of glucose metabolism may reduce complications [6 7]. Although there is much to gain 1998 Blackwell Science Ltd 223

2 224 E. BØG-HANSEN et al. from appropriate treatment and comprehensive guidelines are at hand, concern exists about how well treatment goals are met [8 9]. Cardiovascular risk factors are known to cluster [10 12], and their effects are not only additive but synergistic [13 15]. In recent years, this concern has focused on the coexistence of high blood pressure and impaired glucose metabolism, typically also associated with dyslipidaemia, in the insulin resistance syndrome [16 17]. The present community-based cross-sectional study conducted in primary health care describes a large cohort of patients treated for hypertension and diabetes in order to explore associations between hypertension and NIDDM and a clinical expression of the insulin resistance syndrome. Subgroups of these patients were identified to examine clustering of risk factors. Control of blood pressure and glucose metabolism achieved by treatment was addressed by current guidelines. Subjects and methods Skara Hypertension and Diabetes Project (SKHYDIP) The Skaraborg Hypertension Project comprises guidelines for the detection, work-up, treatment and control of men and women with hypertension, aiming at improved blood pressure control in the population [18]. It was launched in one geographical half of the county of Skaraborg in 1977, the other half serving as a control area. Special hypertension outpatient clinics were established in all primary health care settings in the programme area, including the city of Skara. Much responsibility was given to specially trained nurses supervised by family physicians. The annually collected data included medical history, current medication, standard physical examination and standard laboratory tests. An evaluation after the first 5-year trial period showed that the programme was feasible and improved blood pressure control costeffectively [19 21]. The stroke incidence in the programme area decreased during the 5-year period [22]. An extended follow-up through to 1987 revealed that the prognosis of patients treated within the programme was better than expected from other comparable studies [23 24]. Since 1982, when the first phase of the project was completed, the hypertension outpatient clinic in Skara has been retained, and hypertensive patients have been treated according to the same principles as during the project period. In the project the criteria for diagnosis of hypertension were related to age [19]. In patients aged years, the blood pressure limits for diagnosis were 170/ 105 mmhg and for above 60 years the limits were 180/ 110 mmhg. The diagnostic criteria were fulfilled when either systolic or diastolic pressure limits were exceeded on three separate occasions. Patients with ongoing treatment for hypertension, however, entered the programme directly. Normal blood pressure was defined as 160/ 95 mmhg and 170/ 105 mmhg, respectively, which were also treatment goals [19]. The principles of the Skaraborg Hypertension Project were followed until 1987, when routines were changed according to new national guidelines [25]. According to these guidelines the definition of hypertension was based only on a diastolic blood pressure 90 mmhg, for all persons older than 20 years and the treatment goal was set at a diastolic blood pressure 90 mmhg. In Skara, the principle of three consecutive blood pressures above or equal to the limit value has been maintained as a diagnostic criterion and a diastolic blood pressure 90 mmhg has been used as a target goal in accordance with clinical praxis at the health care center. In 1993, new national guidelines for diagnosis and treatment of hypertension in patients aged 70 years or above were authorized [26]. Diagnostic criteria were either a diastolic blood pressure 90 mmhg or a systolic blood pressure 160 mmhg. However, systolic blood pressure as a diagnostic criterion has not been adopted in this study as these recommendations were published during the study period. A special outpatient clinic for diabetic patients with a specially educated nurse was organized at the health care center in Skara in The intention has been that all patients with the diagnosis of diabetes residing in the municipality should be followed up at the outpatient clinic at least once a year. Annual check-ups of diabetic patients have been performed corresponding to those in the hypertension clinic. Extended examinations have been carried out concerning vision, examination of retina, peripheral sensibility of vibration and peripheral pulsation, and annual laboratory tests have included HbAlc and for certain patients also microalbuminuria. The criteria for diagnosis of diabetes mellitus have followed WHO recommendations [27]. Diagnosis was confirmed if a patient with classic symptoms of diabetes had one fasting blood glucose value 6.7

3 SKARABORG HYPERTENSION PROJECT 225 mmol L 1 or one nonfasting blood glucose value 11.0 mmol L 1. In patients without symptoms of hyperglycaemia the diagnosis was confirmed by two fasting values 6.7 mmol L 1 or a 2-h value 11.0 mmol L 1 in an oral glucose tolerance test after a standardized 75-g oral glucose load (OGTT). The OGTT was recommended, according to WHO standards, in patients with repeated fasting blood glucose values between 5.6 and 6.6 mmol L 1. This was determined by the patient s family physician. Treatment goals for NIDDM patients have been nonfasting blood glucose values below 10.0 mmol L 1 and HbAlc values below 7.5% [28]. In 1986, the hypertension and diabetes outpatient clinics were combined into one joint clinic with nurses educated in both diseases, as well as in other cardiovascular risks, working together with and being supervised by the family physicians in primary health care. The team also included a dietician and a podiatrist. With the intention of finding means to improve the control of blood pressure and glucose and to study associations between hypertension and diabetes, the Skara Hypertension and Diabetes Project was started in Subjects Only one health care center, and no hospital, is available in Skara, serving a total population of Consequently, practically all residents with known hypertension or known NIDDM have a registered medical record at the health care center. All men and women residing in Skara, who consecutively underwent an annual check-up at the hypertension and diabetes outpatient clinic in Skara from June 1992 to September 1993, were eligible for this study. Methods Surveillance followed the baseline procedure in the Skaraborg Hypertension Project and was conducted by the nurses at the hypertension and diabetes outpatient clinic who were specially trained for this task. Medical history included registration of, for example, acute myocardial infarction, angina pectoris, heart failure, acute stroke, intermittent claudication, diabetes mellitus and smoking habits, according to predefined criteria [19]. A 12-lead electrocardiogram was recorded to be coded according to the Minnesota system [29]. Standard laboratory tests included serum cholesterol, fasting serum triglycerides, fasting blood glucose and, for diabetic patients, HbAlc. Insulin-treated diabetics were tested for nonfasting blood glucose and nonfasting serum triglycerides, as fasting tests for these patients were considered unsuitable. In addition to the samples for routine laboratory tests, four additional samples of blood were drawn (one as plasma, one as whole blood and two as serum) and stored at 82 C for later analyses. Supine (5 min rest), and standing (1 min) systolic and diastolic (phase V) right brachial arterial pressures were recorded to the nearest 2 mmhg using Tricuff for automatic adjustment of cuff size to arm circumference [30]. Heart rate was registered simultaneously. Height (to the nearest cm) and weight (to the nearest 0.1 kg) were also recorded as were waist and hip circumferences (both to the nearest cm). The body mass index (BMI) was calculated using the formula weight (kg), length 2 (m 2 ), and waist hip ratio (WHR) by dividing the waist circumference (cm) by the hip circumference (cm). A previously tested questionnaire, enquiring about smoking habits, use of alcohol and habits of physical activity, was completed. Further examination of blood glucose level was performed in nondiabetic patients with hypertension if the fasting blood glucose value was 6.7 mmol L 1. First, a second fasting value was taken. If this still exceeded 6.6 mmol L 1 the diagnosis of NIDDM was ascertained. If the second fasting blood glucose value was between 5.6 and 6.6 mmol L 1 an OGTT was performed. Patients with a second blood glucose value below 5.6 mmol L 1, however, followed the usual clinical praxis at the health care center and did not go through further examinations. In patients with a fasting blood glucose value between 5.6 and 6.6 mmol L 1 at the first visit, the need for further follow-up was determined by the patient s family physician. Diabetic patients without a diagnosis of hypertension who had a diastolic blood pressure above or equal to 90 mmhg were followed up with three consecutive blood pressures. A diagnosis of hypertension was set only if all three diastolic pressures were at least 90 mmhg. Patients with cholesterol values above 6.5 mmol L 1 (2.5 g L 1 ) or triglyceride values above 2.2 mmol L 1 were given extra dietary instructions. The decision of further analysis or pharmacological treatment of hyperlipidaemia was effected by the patient s family physician.

4 226 E. BØG-HANSEN et al. Diabetic patients with hypertension diagnosed during the surveillance period were excluded in the evaluation of blood pressure control, as these patients did not have active treatment of hypertension at the time of registration. Similarly, hypertensive patients with a new diagnosis of diabetes were excluded in the evaluation of treatment control in NIDDM patients. The study population was categorized into three different classes according to age: (1) patients below 40 years of age, (2) patients aged years, and (3) patients aged 70 years or older. Age distribution was also illustrated using 10-year increments from 40 to 79 years, whilst those patients below 40 years of age and those above 79 years of age were each gathered in a single category. Based on clinical criteria (age, weight, symptoms at initial stage, tendency of ketosis, treatment and, in some cases, C-peptid) the diagnosis of diabetes was classified as IDDM or NIDDM. According to hypertension and diabetes status prior to the surveillance, the whole study population was classified by three categories: (I) known hypertension alone, (II) known hypertension and known NIDDM, and (III) known NIDDM alone, i.e. subjects with IDDM were excluded from the current analyses. The number of missing data for men was: BMI (23), WHR (14), fasting blood glucose (47), fasting serum triglycerides (18), serum cholesterol (15), HbAlc (18), smoking (5), and for women: BMI (35), WHR (38), fasting blood glucose (59), fasting serum triglycerides (25), serum cholesterol (22), HbAlc (21), smoking (6). All analyses were stratified by gender. Proportions were compared using the 2 -test and mean values were compared using analyses of covariance with adjustment for age or age plus other covariates. Statistical significance in all analyses was assumed at P All tests were two-sided. The study protocol was approved by the ethics committee of the University in Gothenburg. Results Frequencies of hypertension and NIDDM A total of 1116 patients (488 men and 628 women) were included. Of these, 286 men and 430 women had hypertension alone, 102 men and 102 women hypertension and NIDDM combined, and 100 men and 96 women NIDDM alone (Table 1). The proportion of hypertension among NIDDM patients and the proportion of NIDDM among hypertensive patients are further illustrated in Table 1. Based on diagnoses known at surveillance, the proportion of hypertension among NIDDM patients was 51% and the proportion of NIDDM among hypertensive patients 22%. Taking into account new cases of hypertension and NIDDM identified at the study visit, the proportion of NIDDM among hypertensive patients was 57% and the proportion of NIDDM among hypertensive patients 26%. As shown in Fig. 1 the number of both hypertensive and NIDDM patients increased with increasing age until 80 years. In both genders Table 1 Numbers and proportions of men and women with hypertension (HT) alone, HT and non-insulin-dependent diabetes mellitis (NIDDM) combined and NIDDM alone, as well as proportions of NIDDM amongst patients with HT and proportions of HT amongst patients with NIDDM Men Women 70 years 70 years All 70 years 70 years All (n 275) (n 213) (n 488) (n 321) (n 307) (n 628) n (%) n (%) n (%) n (%) n (%) n (%) HT alone 179 (65.1) 107 (50.2) 286 (58.6) 242 (75.4) 188 (61.2) 430 (68.5) HT and NIDDM 042 (15.3) 060 (28.2) 102 (20.9) 040 (12.5) 062 (20.2) 102 (16.2) NIDDM alone 054 (19.6) 046 (21.6) 100 (20.5) 039 (12.1) 057 (18.6) 096 (15.3) Known diagnoses HT among NIDDM patients 042 (44) 060 (57) 102 (50) 040 (51) 062 (52) 102 (52) NIDDM among HT patients 042 (19) 060 (36) 102 (26) 040 (14) 062 (25) 102 (19) Known and new diagnoses* HT among NIDDM patients 049 (49) 070 (63) 119 (56) 049 (58) 072 (58) 121 (58) NIDDM among HT patients 049 (22) 070 (41) 119 (30) 049 (17) 072 (28) 121 (22) *At surveillance HT was identified in seven men and eight women with known NIDDM, and NIDDM was identified in 10 men and 11 women with known HT.

5 SKARABORG HYPERTENSION PROJECT 227 Number <40 Hypertension alone Hypertension and NIDDM NIDDM alone 40Ð49 50Ð59 60Ð69 70Ð79 >80 Age (years) Fig. 1 Numbers of men and women with known diagnosis of: hypertension alone, hypertension and non-insulin-dependent diabetes mellitus (NIDDM) combined, and NIDDM alone, according to their age and sex. Left-hand bars represent men, right-hand bars represent women. the proportion of patients with hypertension and NIDDM combined increased with increasing age. A relative female preponderance was confined to hypertensive patients. Of the patients with hypertension, 14% had only nonpharmacological treatment; 51% were treated with one, 28% with two, and 7% with three drugs or more. Of the patients with NIDDM, 37% had only nonpharmacological treatment, 40% were treated with oral drugs, 22% with insulin, and 1% with oral drugs combined with insulin. Patients with NIDDM alone were more often treated with insulin than those with both NIDDM and hypertension (20% and 13%, respectively, P 0.05). Age differences In each gender, patients with both hypertension and NIDDM were significantly older than patients with hypertension alone (Table 2 (men); Table 3 (women)). However, there was no difference in age between patients with hypertension and NIDDM combined and patients with NIDDM alone. Blood pressure In each gender, systolic blood pressure, and in women also diastolic blood pressure, was higher in those with hypertension combined with NIDDM than in those with hypertension alone, when adjusted for differences in age (Tables 2 and 3). These blood pressure differences remained even after adjustment for differences in BMI and previous cardiovascular disease. Table 4 shows achieved blood pressure levels. A diastolic blood pressure 90 mmhg was attained by 71% of men and 84% of women. A diastolic pressure 100 mmhg, however, was achieved by almost all patients. A systolic blood pressure 160 mmhg was achieved by 64% of men and 61% of women. Blood pressures, especially systolic pressure, were less well controlled in the elderly. The proportions of well-controlled diastolic and systolic blood pressure were higher in those with hypertension alone than in those with both hypertension and NIDDM (systolic pressure 160 mmhg P both genders, diastolic pressure 90 mmhg P 0.07 men and P women). Table 2 Characteristics of men with hypertension (HT) alone, HT and non-insulin-dependent diabetes mellitus (NIDDM) combined, and NIDDM alone. Previous cardiovascular disease includes previous acute myocardial infarction, angina pectoris or acute stroke HT alone (I) HT and NIDDM (II) NIDDM alone (III) n 286 n 102 n 100 I vs. II II vs. III Mean (SD) Mean (SD) Mean (SD) P P Age (years) (11.9) (9.2) (9.5) Systolic blood pressure (mmhg) (18.5) (20.8) (20.6) Diastolic blood pressure (mmhg) (7.6) (8.9) (9.0) Body mass index (kg m 2 ) (3.6) (4.3) (4.2) Waist hip ratio (0.06) (0.07) (0.07) Fasting blood glucose level (mmol L 1 ) (0.8) (2.1) (2.5) (mg/dl) 099 0(14) 144 0(37) 155 (44) Fasting serum triglyceride level (mmol L 1 ) (1.3) (1.5) (0.9) (mg/dl) 177 (120) 207 (131) 164 (80) Serum cholestrol level (mmol L 1 ) (1.2) (1.1) (1.2) (mg/dl) 244 0(47) 233 0(41) 235 (45) HbAlc (%) (1.4) (1.5) Previous cardiovascular disease 055 0(19.2) 027 0(26.5) 015 (15.0) Smoking (current) 040 0(14.0) 018 0(17.8) 025 (26.0)

6 228 E. BØG-HANSEN et al. Table 3 Characteristics of women with hypertension (HT) alone, HT and non-insulin-dependent diabetes mellitus (NIDDM) combined, and NIDDM alone. Previous cardiovascular disease includes previous acute myocardial infarction, angina pectoris or acute stroke HT alone (I) HT and NIDDM (II) NIDDM alone (III) n 430 n 102 n 96 I vs. II II vs. III Mean (SD) Mean (SD) Mean (SD) P P Age (years) (12.1) (9.8) (10.7) Systolic blood pressure (mmhg) (19.0) (19.5) (21.5) Diastolic blood pressure (mmhg) (9.4) (9.4) (9.5) Body mass index (kg m 2 ) (5.1) (4.5) (5.1) Waist hip ratio (0.07) (0.07) (0.07) Fasting blood glucose level (mmol L 1 ) (0.7) (2.5) (2.9) (mg/dl) 096 (13) 147 0(44) 163 0(52) Fasting serum triglyceride level (mmol L 1 ) (0.9) (1.2) (1.4) (mg/dl) 156 (82) 212 (111) 189 (129) Serum cholestrol level (mmol L 1 ) (1.3) (1.4) (1.2) (mg/dl) 263 (49) 259 0(53) 249 0(46) HbAlc (%) (1.4) (1.8) Previous cardiovascular disease 080 (18.6) 025 0(24.5) 014 0(14.6) Smoking (current) 043 (10.0) 013 0(12.9) 011 0(12.0) Glucose and HbAlc levels Table 5 shows the achieved HbAlc and fasting blood glucose levels. Proportions achieving treatment goals were similar in men and women. HbAlc 7.5% was achieved by 71% of men and 70% of women. In men with NIDDM alone the proportion with HbAlc 6.5% was 47% and in men with both NIDDM and hypertension 61% (P 0.052). Corresponding proportions reaching a fasting blood glucose value 6.7 mmol L 1 were 17% (NIDDM alone) and 31% (NIDDM and hypertension) (P 0.038). In women there were no significant differences of this kind. In patients with hypertension without known or new NIDDM the proportion with a fasting blood glucose value exceeding 5.5 mmol L 1 was 35% (men 38% and women 33%). Lipids Fasting triglyceride levels were higher in patients with NIDDM and hypertension combined than in those with hypertension alone (both sexes), and in those with NIDDM alone (men) (Tables 2 and 3). Adjusting for differences in BMI or WHR, the difference between the combined group and hypertension (women) and between the combined group and NIDDM (men) remained. In men, fasting cholesterol levels were highest in those with hypertension alone compared with those with both hypertension and NIDDM. This difference remained when adjusting for differences in WHR, but was lost when BMI was substituted as covariate for WHR. Body weights In both sexes BMI was higher in those with both NIDDM and hypertension than in those with either NIDDM or hypertension alone. WHR was higher in women with both NIDDM and hypertension than in those with hypertension alone. Discussion This community-based study revealed a more common coexistence of hypertension and diabetes in both genders than previously demonstrated in Swedish primary care [31]. In both genders, cardiovascular risk factors accumulated in patient with both hypertension and NIDDM and, furthermore, blood pressure was less controlled in these patients than in those with hypertension alone. The multiple risk factor clustering in patients with hypertension and NIDDM combined should be addressed clinically and in further studies. Compared to current guidelines and local target goals the control of hypertension and NIDDM in the whole study population seemed appropriate. Recent studies, however, indicate that a more intensive treatment of NIDDM is probably more profitable than lowering diastolic blood pressure further [4 6]. In both genders, the coexistence of hypertension and NIDDM was associated with higher systolic and

7 SKARABORG HYPERTENSION PROJECT 229 Table 4 Achievement of treatment goals by categories of diastolic blood pressure (DBP) and systolic blood pressure (SBP) in men and women; patients with hypertension alone, patients with hypertension and non-insulin-dependent diabetes mellinus (NIDDM) combined, and all hypertensives Hypertension alone Hypertension and NIDDM combined All hypertensives 70 years 70 years All 70 years 70 years All 70 years 70 years All n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) MEN DBP (mmhg) (72) 085 (79) 214 (75) 23 (55) 40 (67) 063 (62) 152 (69) 125 (75) 277 (71) (86) 097 (91) 251 (88) 32 (76) 51 (85) 083 (81) 186 (84) 148 (89) 334 (86) (97) 105 (98) 278 (97) 39 (93) 59 (98) 098 (96) 212 (96) 164 (98) 376 (97) SBP (mmhg) (42) 014 (13) 089 (31) 07 (17) 03 (5) 010 (10) 082 (37) 017 (10) 099 (26) (83) 053 (50) 113 (71) 21 (50) 24 (40) 045 (44) 170 (77) 077 (47) 247 (64) (97) 094 (88) 268 (94) 35 (83) 41 (68) 076 (75) 209 (95) 135 (81) 344 (89) WOMEN DBP (mmhg) (85) 166 (88) 372 (87) 26 (65) 46 (74) 072 (71) 232 (82) 212 (85) 444 (83) (90) 179 (95) 398 (93) 33 (83) 56 (90) 089 (87) 252 (89) 235 (94) 487 (92) (98) 185 (98) 423 (98) 39 (98) 61 (98) 100 (98) 277 (98) 246 (98) 523 (98) SBP (mmhg) (35) 023 (12) 108 (25) 06 (15) 03 (5) 009 (9) 091 (32) 026 (10) 117 (22) (77) 088 (47) 275 (64) 24 (60) 24 (39) 048 (47) 211 (75) 112 (45) 323 (61) (97) 160 (85) 394 (92) 34 (85) 48 (77) 082 (80) 268 (95) 208 (83) 476 (89) diastolic blood pressures, BMI, WHR and fasting serum triglyceride levels, factors that together with impaired glucose metabolism cluster in the insulin resistance syndrome [16 17]. The combination of hypertension and NIDDM appears to be a clinically important recognition of this syndrome. The aggregation of cardiovascular risk factors should be recognized and addressed to improve prevention in these patients. The results confirm and emphasize previously reported accumulation of cardiovascular risk Table 5 Achievement of treatment goals by categories of HbAl and fasting blood glucose level in men and women; patients with NIDDM alone, patients with hypertension and non-insulin-dependent diabetes mellinus (NIDDM) combined, and all patients with NIDDM Hypertension and NIDDM combined NIDDM alone All NIDDM 70 years 70 years All 70 years 70 years All 70 years 70 years All n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) MEN HbAlc (%) (63) 30 (60) 55 (61) 21 (43) 23 (51) 44 (47) 46 (52) 53 (56) 099 (54) (73) 38 (76) 67 (74) 31 (63) 33 (73) 64 (68) 60 (67) 71 (75) 131 (71) Fasting blood glucose level (mmol L 1 ) (27) 17 (34) 27 (31) 08 (18) 06 (16) 14 (17) 18 (22) 23 (26) 041 (24) (43) 30 (60) 46 (53) 20 (45) 17 (46) 37 (46) 36 (44) 47 (54) 083 (49) WOMEN HbAlc (%) (61) 23 (43) 43 (50) 17 (45) 27 (51) 44 (48) 37 (52) 50 (47) 087 (49) (73) 42 (79) 65 (77) 23 (61) 35 (66) 58 (64) 47 (66) 77 (73) 124 (70) Fasting blood glucose level (mmol L 1 ) (51) 10 (20) 28 (33) 04 (18) 10 (21) 14 (20) 22 (39) 20 (20) 042 (27) (69) 21 (41) 45 (52) 09 (41) 17 (36) 26 (38) 33 (58) 38 (39) 071 (46)

8 230 E. BØG-HANSEN et al. factors in clinically identified subjects with NIDDM and hypertension [12]. However, the worse control of hypertension in patients with both diseases was not expected. Higher blood pressure levels in these patients might reflect a reduced efficacy of antihypertensive drugs as they hardly improve, but may reduce, insulin sensitivity [32 33]. Means to increase insulin sensitivity, both nonpharmacologically and pharmacologically, should be further tried to reduce risk factor levels in these patients. Men and women with NIDDM alone were leaner, were more often treated with insulin, and the control of glucose metabolism in these patients was worse, than in those with both NIDDM and hypertension combined. Consequently, the former group also appeared to be a distinguished entity. A less than ideal glucose control in diabetic patients was mainly restricted to this subgroup. In comparison with current guidelines, there is room for further improvement in the control of glucose metabolism in patients with NIDDM. This should be emphasized, as recent studies in diabetes, both NIDDM and IDDM, demonstrate improved prognosis with more intense treatment and better glucose control [6 7]. The current Swedish treatment goal for hypertension has focused on 90 mmhg diastolic blood pressure. A Swedish multicenter study, mainly in primary care, included middle aged hypertensives and found treated diastolic blood pressure 90 mmhg in 57% of men and in 60% of women [31]. Similarly, a European multicenter study reported corresponding proportions of patients with a diatolic blood pressure 90 mmhg in less than half of their study population [34]. These studies included patients reported voluntarily by interested physicians and the results are probably not worse than those achieved in general. In patients with hypertension alone, comprising the majority of hypertensives in both genders, a much higher degree of attainment of treatment goals was seen in the present study. This may be credited to the structured care using strict local guidelines and specially trained nurses. In the first phase of the Skaraborg Hypertension Project it was demonstrated that structured hypertension care improved blood pressure control in treated hypertensives at reduced costs, compared with a reference area [19 21]. This is also supported by other studies [35 36]. However, a systolic blood pressure above 160 mmhg occurred frequently in both men and women and more so in the elderly. Apart from the increasing systolic blood pressure by age, this finding might also be explained by the negligence of systolic blood pressure in national guidelines. There is probably more to be gained from focusing on systolic blood pressure than from further reducing the diastolic blood pressure, thus accounting also for the J-shaped relationship between risk and treated diastolic blood pressure observed in this and other populations [4 5]. In this category of hypertensive patients without known diabetes, there may still be a subgroup with insulin resistance of clinical importance as impaired glucose tolerance (IGT) was not systematically ascertained by OGTT and thus not accounted for. A high prevalence of hypertension among NIDDM patients has been reported from primary care elsewhere [6, 12]. However, the prevalence of NIDDM among hypertensive patients was higher than expected from other studies. A recent Swedish multicenter study [31] reported 11.1% diabetes among hypertensive men aged years and 9.1% diabetes among hypertensive women aged years. One explanation could be a recruitment bias. Most patients with both NIDDM and hypertension are now treated in organized teams in diabetes outpatient clinics, and diagnosis of hypertension is well ascertained in this category. Thus, hypertensive patients identified outside diabetes outpatient clinics often exclude those with diabetes. In Skara, with a joint outpatient clinic for hypertension and diabetes in primary care and no other providers of medical care in the community, both diagnoses, as well as the relations of both diseases, were well ascertained. However, a hospital-based hypertension outpatient clinic in Göteborg reports a high cumulative incidence of diabetes, 21%, during 15 years of follow-up of hypertensive men in the Primary Prevention Trial in Göteborg with the initial prevalence of 3.9% [33]. Based on the presented observations, distinguished forms of both hypertension and NIDDM can be clinically identified. The pathogenetic background could thus be better identified and addressed in treatment regimens in subgroups of patients with hypertension and NIDDM. Patients with both hypertension and NIDDM comprise a clinically defined group at high risk. New strategies to improve blood pressure control in these patients are needed and should focus on nonpharmacological approaches and other means to reduce insulin resistance. Further improvement could be achieved by better control of all concomitant risk factors.

9 SKARABORG HYPERTENSION PROJECT 231 Acknowledgement This study was supported by grants from the Swedish Heart Lung Foundation, the Swedish Medical Research Council, National Public Health Institute, Skaraborg Institute, Skaraborg County Council, the NEPI Foundation (The Swedish Network for Pharmacoepidemiology) and the Faculty of Medicine, Lund University. References 1 SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). J Am Med Assoc 1991; 265: Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, et al. Blood pressure, stroke, and coronary heart disease. Part 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: Whisnant JP. The decline of stroke. Stroke 1984; 15: Farnett L, Mulrow CD, Linn WD, Lucey CR, Tuley MR. The J- curve phenomenon and the treatment of hypertension. Is there a point beyond which pressure reduction is dangerous? J Am Med Assoc 1991; 265: Lindblad U, Råstam L, Rydén L, Ranstam J, Isacsson S-O, Berglund G. Control of blood pressure and risk of first acute myocardial infarction: Skaraborg Hypertension Project. Br Med J 1994; 308: Andersson DKG, Svärdsudd K. Long-term glycemic control relates to mortality in type II diabetes. Diabetes Care 1996; 18: Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: Swales JD. Management guidelines for hypertension: is anyone taking notice? J Hum Hypertens 1995; 9: Editorial. Type 2 diabetes or NIDDM: looking for a better name. Lancet 1989; i: Criqui MH, Barrett-Connor E, Holdbrook MJ, Austin M, Turner JD. Clustering of cardiovascular disease risk factors. Prev Med 1980; 9: Bønaa K, Thelle D. Association between blood pressure and serum lipids in a population. The Tromsø Study. Circulation 1991; 83: The Hypertension in Diabetes Study Group. Hypertension in diabetes study (HDS): I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factor for cardiovascular and diabetic complications. J Hypertens 1993; 11: Kannel WB. Status of risk factors and their consideration in antihypertensive therapy. Am J Cardiol 1987; 59: 80A 90A. 14 Samuelsson O, Wilhelmsen L, Andersson OK, Pennert K, Berglund G. Cardiovascular morbidity in relation to change in blood pressure and serum cholesterol levels in treated hypertension. Results from the Primary Prevention Trial in Göteborg, Sweden. J Am Med Assoc 1987; 258: The Hypertension in Diabetes Study Group. Hypertension in diabetes study (HDS): II. Increased risk of cardiovascular complications in hypertensive type 2 diabetic patients. 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Reduced stroke incidence with structured hypertension care: The Skaraborg Hypertension Project. J Hypertens 1990; 8: Lindblad U, Råstam L, Ranstam J. Stroke morbidity in patients treated for hypertension: The Skaraborg Hypertension Project. J Intern Med 1993; 233: Lindblad U, Råstam L, Ranstam J. Acute myocardial infarction in patients treated for hypertension in The Skaraborg Hypertension Project. Eur Heart J 1993; 14: Treatment of mild hypertension. Stockholm: National Board of Health and Welfare, Drug Information Committee, Sweden, 1987: Behandling av hypertoni hos äldre. Stockholm: Information från Läkemedelsverket, 1993; 1 (in Swedish). 27 World Health Organization Expert Committee. Diabetes mellitus. Technical Report series no. 742, Geneva, Switzerland Treatment of non-insulin-dependent diabetes mellitus. Stockholm: Medical Products Agency, Sweden 1990; Rose GA, Blackburn H, Gillum RF, Prineas RJ. Cardiovascular Survey Methods, 2nd edn. Geneva: World Health Organization 1982; Råstam L, Sjönell G. A new device for measuring blood pressure in adults (Letter). Lancet 1991; 337: Nilsson P, Andersson DKG, Andersson P-E, Schwan Å, Östlind B, Malmborg R, Lithell H. Cardiovascular risk factors in treated hypertensives a nationwide, cross-sectional study in Sweden. J Intern Med 1993; 233: Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med 1989; 321: Samuelsson O, Hedner T, Berglund G, Persson B, Andersson OK, Wilhelmsen L. Diabetes mellitus in treated hypertension: incidence, predictive factors and the impact of non-selective beta-blockers and thiazide diuretics during 15 years treatment of middle-aged hypertensive men in the Primary Prevention Trial Göteborg, Sweden. J Hum Hypertens 1994; 8: Hosie J, Wiklund I. Managing hypertension in general practice: can we do better? 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10 232 E. BØG-HANSEN et al. prehensive five-year community programme to control cardiovascular diseases (North Karelia project). Br Med J 1979; 2: O Connor PJ, Wagner EH, Strogatz DS. Hypertension control in a rural community. An assessment of community-oriented primary care. J Fam Prac 1990; 30: Received 21 February 1997; accepted 14 October Correspondence: Dr Erik Bøg-Hansen MD, Skara Health Care Center, Malmgatan 36, S Skara, Sweden (fax: ; e- mail: erik.bog-hansen@mailbox.swipnet.se).

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