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Utilization and efficacy of ace inhibition in diabetic hypertension
AJH
2000;13:81A–97A
E001 PLASMA LEPTIN LEVEL DOES NOT PLAY AN IMPORTANT ROLE ON BP REGULATORY MECHANISMS IN DIABETES K. Matsuo*, H. Mikami*, T. Ogihara*, and M.L. Tuck. Osaka University Medical School, Suita City, Osaka, Japan. Sepulveda VA Medical Center, Sepulveda, CA The objective in the present study was to evaluate the effect of insulin on sympathetic activity, plasma leptin and BP levels. In 8 patients with IDDM, 11 patients with NIDDM and 14 healthy, non-diabetic subjects as a control group (BMI: 23.2, 23.5, 23.1 kg/m2, respectively). BMI, BP, HbA1c, fasting blood glucose, insulin (INS), leptin (LEP) and norepinephrine (NE) were measured at entry, week 4, 12 and 24 during insulin therapy for IDDM or troglitazone for NIDDM. BMI did not change during the study. The subjects were men and without diabetic nephropathy or neuropathy, and untreated for diabetes prior to the present study. The goal of treatments for diabetes was defined as less than 6.5% in HbA1c. At entry, plasma INS and NE were less in IDDM than those in NIDDM and in control group, although LEP was similar to each other (INS: IDDM 3.4*, NIDDM 17.4**, control 8.7 U/ml, NE: 146*, 179, 171 pg/ml, LEP: 4.8, 4.9, 4.7 ng/ml, *P⬍0.05 vs control). The patients with IDDM and NIDDM had higher levels in BP than control group at entry (138/86*, 143/89*, 128/75 mmHg). In IDDM treated with insulin administration therapy, BP, INS, LEP, NE increased at week 4, and those elevation remained at week 12 & 24 (week 4: BP 143/90, INS 7.8#, LEP 9.5#, NE 201#, #P⬍0.05 vs entry). In NIDDM treated with troglitazone, INS decreased at week 12, but BP, LEP nor NE did not change (INS 7.7##, LEP 4.5, NE 165). At week 24, INS and LEP, but not NE nor BP, decreased (INS 7.2##, LEP 3.5#, NE 154, BP). At week 12 and 24, plasma LEP in IDDM was higher than that in control and NIDDM, despite BP level in IDDM was similar to those in NIDDM and higher than that in control group. These results demonstrate that plasma insulin appears to affect plasma leptin level chronically, and that plasma insulin and leptin do not play important roles on BP regulatory mechanisms in diabetic patients. Key Words: Diabetes mellitus, leptin, insulin, sympathetic activity E002 HYPERTENSION IN TYPE 2-DIABETIC PATIENTS— EFFECTS OF ENDOGENOUS INSULIN AND ANTIDIABETIC THERAPIES J. Rosenthal* and H. Mauersberger. Ulm University, Med. Ctr. Falmouth, MA (P.O. Box 346) Hypertension is present in almost 50% of newly diagnosed type 2 diabetic patients. Insulin resistance as a possible trigger of both hypertension and type 2 diabetes is usually linked to compensatory hyperinsulinemia. Insulin has been described as increasing sodium reabsorption and stimulating the sympathetic nervous system. The question as to whether high insulin levels enhance the progression of hy© 2000 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
POSTERS: Obesity, Insulin Resistance, Diabetes
pertension was investigated in a long-term clinical study. A total of 76 overweight (BMI: A: 29.1 ⫾ 4.3; G: 28.8 ⫾ 4.3) type 2 diabetic patients with mild hypertension (mean age 57.5 yr) were randomized and treated with acarbose (A, insulinlowering, 3⫻100 mg) or gliben-clamide (G, insulin-enhancing, mean dose 5.1 mg) to compare the long-term blood pressure (BP) profile. Except for intervention by lifestyle modification no antihypertensive therapy was permitted. BP was assessed by 24h monitoring before therapy, after 3 and 6 mo. Laboratory data on glycemic control, lipids and safety were collected. All patients entered ITT analysis, 63 (A: 32; G: 31) entered the per-protocol-analysis. The mean duration of diabetes and hypertension was 20.2 ⫾ 31.2 (A)/30.1 ⫾ 37.0 (G) mo and 35.6 ⫾ 44.8 (A)/31.2 ⫾ 35.4 (G) mo respectively. The weighted 24h systolic and diastolic mean values (mmHg) were 134.9 ⫾ 11.6 (A)/138.5 ⫾ 14.1 (G) and 84.2 ⫾ 6.2 (A)/85.9 ⫾ 6.2 (G) respectively. Fasting insulin level (⬎/⬍ 15 mU/I) stratification showed higher systolic 24h BP (⫹4.5 ⫾ 0.21 mmHg) in the ⬎15 mU/I group, in particular during the day (7 a.m. to 10 p.m.: ⫹5.8 ⫾ 0.11; not statistically significant [p⫽0.11]). Insulin levels (mU/I) were lower in group A (fasting: A: 14.8 ⫾ 8.5; G: 20.5 ⫾ 17.9; p⬍0.05; postprandial: A: 49.3 ⫾ 40.6; G: 61.6 ⫾ 54.8; p⬍0.05). Change of systolic 24h BP (mmHg) over 24 wk was ⫺5.2 ⫾ 2.4 under A (G: ⫺1.6 ⫾ 2.4) (p⫽0.0001), whereas change of diastolic 24h BP (mmHg) over 24 wk was ⫺5.5 ⫾ 1.5 under G (A: ⫺2.4 ⫾ 1.5) (p⫽0.0001). Body weight de-creased under A (⫺6.6 ⫾ 2.5 kg) and increased under G (⫹3.8 ⫾ 3.1 kg). HbA1c improved slightly more under A (7.0 ⫾ 1.436.5 ⫾ 1.2; G: 7.2 ⫾ 1.7 3 7.0 ⫾ 1.6). Different antidiabetics may influence BP in different ways. Conceivably A is useful in the lifestyle modification of type 2 diabetes patients and primarily isolated systolic hypertension. Key Words: Hypertension, type 2 diabetes, insulin levels, acarbose, glibenclamide E003 UTILIZATION AND EFFICACY OF ACE INHIBITION IN DIABETIC HYPERTENSION R. Padwal, R. Tsuyuki, M. Lee, and R.Z. Lewznczuk*. University of Alberta, Edmonton, Canada ACE inhibitors are the agents of choice in the management of diabetic hypertension, yet their antihypertensive efficacy as single agents in diabetes is questionable. The purpose of this study was to ascertain the use and efficacy of ACE inhibitors in diabetic hypertension. This study was carried out in two-parts. The first part consisted of 58 hypertensive, diabetic subjects on ACE inhibitor monotherapy being followed longitudinally with respect to blood pressure control. In the second part of the study, 163 randomly selected hypertensive diabetics in a primary care setting were studied according to blood pressure control and microalbuminuria. Average follow-up for the longitudinal study was 22 months during which time HbA1c fell by 1.1% (p⬍.0001) confirming active intervention. Blood pressure, however, only decreased 3/2 mmHg from a baseline of 149/85 (p⫽.26) even though ACE inhibitor dose was increased in 0895-7061/00/$20.00
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AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
ASH XV ABSTRACTS
75% of patients during the follow-up period. In a separate group of patients treated with an ACE inhibitor and a second antihypertensive agent, blood pressure fell by 14/10 mmHg (p⫽.0007). In the latter case, blood pressure decline was independent of the second agent used. Cross-sectionally, only 45% of hypertensive diabetics were on ACE inhibitor therapy. 27% of patients were on a non-ACE antihypertensive agent and 28% were on no antihypertensive therapy. From the perspective of microalbuminuria, only 51% of patients were on ACE inhibitors with only 5% of normotensive, microalbuminuric patients being on ACE inhibition. Using a cutoff of 130/85, only 30% of hypertensive diabetics met recommended blood pressure goals. Excluding ACE inhibitors, no other single agent proved superior in blood pressure control nor were there differences in efficacy between ACE inhibitor brands. We conclude that ACE inhibitors are underutilized in the management of diabetic hypertension or microalbuminuria. However, when used as single agents, their antihypertensive efficacy is limited suggesting two or more agents may be necessary for blood pressure control in diabetes. Key Words: Diabetes, ACE inhibitors, microalbuminuria
E004 SHORT AND LONG-TERM OUTCOME AFTER ACUTE MYOCARDIAL INFARCTION (AMI) IN PATIENTS WITH DIABETES MELLITUS (DM) AND HYPERTENSION (HT) M. Jonas, E. Grossman*, V. Boyka, and S. Behar. Internal Medicine D. Sheba Medical Center, Tel Hashomer, Israel The outcome after AMI of diabetic patients with and without a history of HT was compared to their Non-diabetic counterparts. 4317 consecutive patients with an AMI admitted to all CCUs in Israel were included in the study and followed for one year. Patients having both DM and HT were likely to be older, female and with a history of AMI, angina and stroke. Blood pressure (BP) (mean ⫾ DS), complications (%) and mortality (%) were:
Key Words: Diabetes mellitus, hypertension, myocardial Infarction E005 SUBPRESSOR DOSE OF L-NAME UNMASKS HYPERTENSIVE EFFECTS OF INSULIN M. Bursztyn*, and J. Mekler. Hadassah University Hospital, Mount Scopus, Jerusalem, Israel We previously found that chronic exogenous hyperinsulinemia without sugar supplementation does not elevate blood pressure (BP). This may be partially explained by insulin’s ability to release nitric oxide (NO) and cause vasodilatation. To test this hypothesis we studied four groups of rats: nine rats [body weight (BW) 213 ⫾ 14 g] treated by a gradual increase of sustained release, subcutaneous insulin pellet (INS); nine rats (BW 213 ⫾ 9 g) treated by L-NAME in drinking water 50 mg/liter (LN); 16 rats (BW 213 ⫾ 14 g) treated by the combination (LNINS); and nine control rats (BW 218 ⫾ 11 g) (CON). BP was followed weekly for six weeks and then rats were studied in metabolic cages. Weight gain was not different during the six weeks. Creatinine clearance and 24-hour urinary Na⫹ excretion were not different between the four groups. Plasma glucose and NO metabolites levels were not significant at weeks 3 and 6. The table shows (means ⫾ SD) systolic BP (SBP) (mmHg)
CON LN INS LNINS
Baseline
Week 3
Week 6
119 ⫾ 15 118 ⫾ 10 118 ⫾ 11 121 ⫾ 9
122 ⫾ 17 118 ⫾ 17 118 ⫾ 24 136 ⫾ 14*
128 ⫾ 14 127 ⫾ 15 118 ⫾ 24 150 ⫾ 14*
* SBP pⱕ0.0001 versus all, by 2 ⫻ 2 ANOVA.
There was no hypoglycemia and, by week 6, fructosamine levels were 2.2 ⫾ 0.4, 2.1 ⫾ 0.2, 2.2 ⫾ 0.2 and 2.3 ⫾ 0.3 mol/L in CON, LN, INS and LNINS, respectively. In conclusion, chronic exogenous hyperinsulinemia does not affect BP but may cause hypertension when endothelial function is compromised. Key Words: Nitric oxide; insulin; blood pressure
Diabetics
Age (years) Female (%) SBP (mm Hg) DBP (mm Hg) Anterior MI AV block CHF Mortality 7-Day 30-Day 1-year
HTⴙ n ⴝ 546
HTⴚ n ⴝ 547
Non-diabetics HTⴙ HTⴚ n ⴝ 1192 n ⴝ 2032
67 ⫾ 10 42.7 142 ⫾ 29 84 ⫾ 36 46.5 7.7 34.8
63 ⫾ 11 27.1 133 ⫾ 25 78 ⫾ 14 45.7 9.5 26.5
66 ⫾ 12 33.2 140 ⫾ 28 82 ⫾ 16 45.8 7.0 22.0
60 ⫾ 13* 16.7* 130 ⫾ 23* 78 ⫾ 13* 44.2 5.6* 15.2*
11.7 16.5 27.6
9.5 15.4 22.9
7.1 11.6 17.6
5.3* 8.0* 11.9*
* p⬍0.01, SBP ⫽ systolic BP, DBP ⫽ diastolic BP, AV ⫽ atrioventricular, CHF ⫽ congestive heart failure. Adjusted risk for 1-year mortality was increased in diabetic patients [1.62 (95% CI; 1.29 –2.04) and 1.55 (95% CI; 1.25–1.93) for those without and those with HT, respectively]. The coexistence of HT did not worsen the outcome of diabetic patients. Thus, in diabetic hypertensive patients BP control rather than glucose control can improve prognosis after MI.
E006 DIABETES AND HYPERTENSION ARE ACCOMPANIED BY IMPAIRED INSULIN-MEDIATED MYOSIN-BOUND PHOSPHATASE ACTIVATION AND VASCULAR SMOOTH MUSCLE CELL RELAXATION DUE TO DEFECTIVE RHO KINASE AND NITRIC OXIDE SYNTHASE SIGNALING O. Sandu, N. Duddy, L. Ragolia, and N. Begum*. Diabetes Research Laboratory, Winthrop University Hospital, Mineola, NY and Department of Medicine, SUNY @ Stony Brook, NY Increased contractility and defective relaxation of vascular smooth muscle cells (VSMCs) are the earliest abnormalities observed in diabetes (DM) and hypertension (HT). Insulin can inhibit VSMC contraction, migration and growth in the normal vasculature and insulin’s failure to do so in insulin resistant states may contribute to enhanced atherosclerosis. We have recently demonstrated that insulin rapidly acti-
2000;13:81A–97A
E001 PLASMA LEPTIN LEVEL DOES NOT PLAY AN IMPORTANT ROLE ON BP REGULATORY MECHANISMS IN DIABETES K. Matsuo*, H. Mikami*, T. Ogihara*, and M.L. Tuck. Osaka University Medical School, Suita City, Osaka, Japan. Sepulveda VA Medical Center, Sepulveda, CA The objective in the present study was to evaluate the effect of insulin on sympathetic activity, plasma leptin and BP levels. In 8 patients with IDDM, 11 patients with NIDDM and 14 healthy, non-diabetic subjects as a control group (BMI: 23.2, 23.5, 23.1 kg/m2, respectively). BMI, BP, HbA1c, fasting blood glucose, insulin (INS), leptin (LEP) and norepinephrine (NE) were measured at entry, week 4, 12 and 24 during insulin therapy for IDDM or troglitazone for NIDDM. BMI did not change during the study. The subjects were men and without diabetic nephropathy or neuropathy, and untreated for diabetes prior to the present study. The goal of treatments for diabetes was defined as less than 6.5% in HbA1c. At entry, plasma INS and NE were less in IDDM than those in NIDDM and in control group, although LEP was similar to each other (INS: IDDM 3.4*, NIDDM 17.4**, control 8.7 U/ml, NE: 146*, 179, 171 pg/ml, LEP: 4.8, 4.9, 4.7 ng/ml, *P⬍0.05 vs control). The patients with IDDM and NIDDM had higher levels in BP than control group at entry (138/86*, 143/89*, 128/75 mmHg). In IDDM treated with insulin administration therapy, BP, INS, LEP, NE increased at week 4, and those elevation remained at week 12 & 24 (week 4: BP 143/90, INS 7.8#, LEP 9.5#, NE 201#, #P⬍0.05 vs entry). In NIDDM treated with troglitazone, INS decreased at week 12, but BP, LEP nor NE did not change (INS 7.7##, LEP 4.5, NE 165). At week 24, INS and LEP, but not NE nor BP, decreased (INS 7.2##, LEP 3.5#, NE 154, BP). At week 12 and 24, plasma LEP in IDDM was higher than that in control and NIDDM, despite BP level in IDDM was similar to those in NIDDM and higher than that in control group. These results demonstrate that plasma insulin appears to affect plasma leptin level chronically, and that plasma insulin and leptin do not play important roles on BP regulatory mechanisms in diabetic patients. Key Words: Diabetes mellitus, leptin, insulin, sympathetic activity E002 HYPERTENSION IN TYPE 2-DIABETIC PATIENTS— EFFECTS OF ENDOGENOUS INSULIN AND ANTIDIABETIC THERAPIES J. Rosenthal* and H. Mauersberger. Ulm University, Med. Ctr. Falmouth, MA (P.O. Box 346) Hypertension is present in almost 50% of newly diagnosed type 2 diabetic patients. Insulin resistance as a possible trigger of both hypertension and type 2 diabetes is usually linked to compensatory hyperinsulinemia. Insulin has been described as increasing sodium reabsorption and stimulating the sympathetic nervous system. The question as to whether high insulin levels enhance the progression of hy© 2000 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
POSTERS: Obesity, Insulin Resistance, Diabetes
pertension was investigated in a long-term clinical study. A total of 76 overweight (BMI: A: 29.1 ⫾ 4.3; G: 28.8 ⫾ 4.3) type 2 diabetic patients with mild hypertension (mean age 57.5 yr) were randomized and treated with acarbose (A, insulinlowering, 3⫻100 mg) or gliben-clamide (G, insulin-enhancing, mean dose 5.1 mg) to compare the long-term blood pressure (BP) profile. Except for intervention by lifestyle modification no antihypertensive therapy was permitted. BP was assessed by 24h monitoring before therapy, after 3 and 6 mo. Laboratory data on glycemic control, lipids and safety were collected. All patients entered ITT analysis, 63 (A: 32; G: 31) entered the per-protocol-analysis. The mean duration of diabetes and hypertension was 20.2 ⫾ 31.2 (A)/30.1 ⫾ 37.0 (G) mo and 35.6 ⫾ 44.8 (A)/31.2 ⫾ 35.4 (G) mo respectively. The weighted 24h systolic and diastolic mean values (mmHg) were 134.9 ⫾ 11.6 (A)/138.5 ⫾ 14.1 (G) and 84.2 ⫾ 6.2 (A)/85.9 ⫾ 6.2 (G) respectively. Fasting insulin level (⬎/⬍ 15 mU/I) stratification showed higher systolic 24h BP (⫹4.5 ⫾ 0.21 mmHg) in the ⬎15 mU/I group, in particular during the day (7 a.m. to 10 p.m.: ⫹5.8 ⫾ 0.11; not statistically significant [p⫽0.11]). Insulin levels (mU/I) were lower in group A (fasting: A: 14.8 ⫾ 8.5; G: 20.5 ⫾ 17.9; p⬍0.05; postprandial: A: 49.3 ⫾ 40.6; G: 61.6 ⫾ 54.8; p⬍0.05). Change of systolic 24h BP (mmHg) over 24 wk was ⫺5.2 ⫾ 2.4 under A (G: ⫺1.6 ⫾ 2.4) (p⫽0.0001), whereas change of diastolic 24h BP (mmHg) over 24 wk was ⫺5.5 ⫾ 1.5 under G (A: ⫺2.4 ⫾ 1.5) (p⫽0.0001). Body weight de-creased under A (⫺6.6 ⫾ 2.5 kg) and increased under G (⫹3.8 ⫾ 3.1 kg). HbA1c improved slightly more under A (7.0 ⫾ 1.436.5 ⫾ 1.2; G: 7.2 ⫾ 1.7 3 7.0 ⫾ 1.6). Different antidiabetics may influence BP in different ways. Conceivably A is useful in the lifestyle modification of type 2 diabetes patients and primarily isolated systolic hypertension. Key Words: Hypertension, type 2 diabetes, insulin levels, acarbose, glibenclamide E003 UTILIZATION AND EFFICACY OF ACE INHIBITION IN DIABETIC HYPERTENSION R. Padwal, R. Tsuyuki, M. Lee, and R.Z. Lewznczuk*. University of Alberta, Edmonton, Canada ACE inhibitors are the agents of choice in the management of diabetic hypertension, yet their antihypertensive efficacy as single agents in diabetes is questionable. The purpose of this study was to ascertain the use and efficacy of ACE inhibitors in diabetic hypertension. This study was carried out in two-parts. The first part consisted of 58 hypertensive, diabetic subjects on ACE inhibitor monotherapy being followed longitudinally with respect to blood pressure control. In the second part of the study, 163 randomly selected hypertensive diabetics in a primary care setting were studied according to blood pressure control and microalbuminuria. Average follow-up for the longitudinal study was 22 months during which time HbA1c fell by 1.1% (p⬍.0001) confirming active intervention. Blood pressure, however, only decreased 3/2 mmHg from a baseline of 149/85 (p⫽.26) even though ACE inhibitor dose was increased in 0895-7061/00/$20.00
82A
AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2
ASH XV ABSTRACTS
75% of patients during the follow-up period. In a separate group of patients treated with an ACE inhibitor and a second antihypertensive agent, blood pressure fell by 14/10 mmHg (p⫽.0007). In the latter case, blood pressure decline was independent of the second agent used. Cross-sectionally, only 45% of hypertensive diabetics were on ACE inhibitor therapy. 27% of patients were on a non-ACE antihypertensive agent and 28% were on no antihypertensive therapy. From the perspective of microalbuminuria, only 51% of patients were on ACE inhibitors with only 5% of normotensive, microalbuminuric patients being on ACE inhibition. Using a cutoff of 130/85, only 30% of hypertensive diabetics met recommended blood pressure goals. Excluding ACE inhibitors, no other single agent proved superior in blood pressure control nor were there differences in efficacy between ACE inhibitor brands. We conclude that ACE inhibitors are underutilized in the management of diabetic hypertension or microalbuminuria. However, when used as single agents, their antihypertensive efficacy is limited suggesting two or more agents may be necessary for blood pressure control in diabetes. Key Words: Diabetes, ACE inhibitors, microalbuminuria
E004 SHORT AND LONG-TERM OUTCOME AFTER ACUTE MYOCARDIAL INFARCTION (AMI) IN PATIENTS WITH DIABETES MELLITUS (DM) AND HYPERTENSION (HT) M. Jonas, E. Grossman*, V. Boyka, and S. Behar. Internal Medicine D. Sheba Medical Center, Tel Hashomer, Israel The outcome after AMI of diabetic patients with and without a history of HT was compared to their Non-diabetic counterparts. 4317 consecutive patients with an AMI admitted to all CCUs in Israel were included in the study and followed for one year. Patients having both DM and HT were likely to be older, female and with a history of AMI, angina and stroke. Blood pressure (BP) (mean ⫾ DS), complications (%) and mortality (%) were:
Key Words: Diabetes mellitus, hypertension, myocardial Infarction E005 SUBPRESSOR DOSE OF L-NAME UNMASKS HYPERTENSIVE EFFECTS OF INSULIN M. Bursztyn*, and J. Mekler. Hadassah University Hospital, Mount Scopus, Jerusalem, Israel We previously found that chronic exogenous hyperinsulinemia without sugar supplementation does not elevate blood pressure (BP). This may be partially explained by insulin’s ability to release nitric oxide (NO) and cause vasodilatation. To test this hypothesis we studied four groups of rats: nine rats [body weight (BW) 213 ⫾ 14 g] treated by a gradual increase of sustained release, subcutaneous insulin pellet (INS); nine rats (BW 213 ⫾ 9 g) treated by L-NAME in drinking water 50 mg/liter (LN); 16 rats (BW 213 ⫾ 14 g) treated by the combination (LNINS); and nine control rats (BW 218 ⫾ 11 g) (CON). BP was followed weekly for six weeks and then rats were studied in metabolic cages. Weight gain was not different during the six weeks. Creatinine clearance and 24-hour urinary Na⫹ excretion were not different between the four groups. Plasma glucose and NO metabolites levels were not significant at weeks 3 and 6. The table shows (means ⫾ SD) systolic BP (SBP) (mmHg)
CON LN INS LNINS
Baseline
Week 3
Week 6
119 ⫾ 15 118 ⫾ 10 118 ⫾ 11 121 ⫾ 9
122 ⫾ 17 118 ⫾ 17 118 ⫾ 24 136 ⫾ 14*
128 ⫾ 14 127 ⫾ 15 118 ⫾ 24 150 ⫾ 14*
* SBP pⱕ0.0001 versus all, by 2 ⫻ 2 ANOVA.
There was no hypoglycemia and, by week 6, fructosamine levels were 2.2 ⫾ 0.4, 2.1 ⫾ 0.2, 2.2 ⫾ 0.2 and 2.3 ⫾ 0.3 mol/L in CON, LN, INS and LNINS, respectively. In conclusion, chronic exogenous hyperinsulinemia does not affect BP but may cause hypertension when endothelial function is compromised. Key Words: Nitric oxide; insulin; blood pressure
Diabetics
Age (years) Female (%) SBP (mm Hg) DBP (mm Hg) Anterior MI AV block CHF Mortality 7-Day 30-Day 1-year
HTⴙ n ⴝ 546
HTⴚ n ⴝ 547
Non-diabetics HTⴙ HTⴚ n ⴝ 1192 n ⴝ 2032
67 ⫾ 10 42.7 142 ⫾ 29 84 ⫾ 36 46.5 7.7 34.8
63 ⫾ 11 27.1 133 ⫾ 25 78 ⫾ 14 45.7 9.5 26.5
66 ⫾ 12 33.2 140 ⫾ 28 82 ⫾ 16 45.8 7.0 22.0
60 ⫾ 13* 16.7* 130 ⫾ 23* 78 ⫾ 13* 44.2 5.6* 15.2*
11.7 16.5 27.6
9.5 15.4 22.9
7.1 11.6 17.6
5.3* 8.0* 11.9*
* p⬍0.01, SBP ⫽ systolic BP, DBP ⫽ diastolic BP, AV ⫽ atrioventricular, CHF ⫽ congestive heart failure. Adjusted risk for 1-year mortality was increased in diabetic patients [1.62 (95% CI; 1.29 –2.04) and 1.55 (95% CI; 1.25–1.93) for those without and those with HT, respectively]. The coexistence of HT did not worsen the outcome of diabetic patients. Thus, in diabetic hypertensive patients BP control rather than glucose control can improve prognosis after MI.
E006 DIABETES AND HYPERTENSION ARE ACCOMPANIED BY IMPAIRED INSULIN-MEDIATED MYOSIN-BOUND PHOSPHATASE ACTIVATION AND VASCULAR SMOOTH MUSCLE CELL RELAXATION DUE TO DEFECTIVE RHO KINASE AND NITRIC OXIDE SYNTHASE SIGNALING O. Sandu, N. Duddy, L. Ragolia, and N. Begum*. Diabetes Research Laboratory, Winthrop University Hospital, Mineola, NY and Department of Medicine, SUNY @ Stony Brook, NY Increased contractility and defective relaxation of vascular smooth muscle cells (VSMCs) are the earliest abnormalities observed in diabetes (DM) and hypertension (HT). Insulin can inhibit VSMC contraction, migration and growth in the normal vasculature and insulin’s failure to do so in insulin resistant states may contribute to enhanced atherosclerosis. We have recently demonstrated that insulin rapidly acti-