Blood Pressure and Kidney Disease in Type 1 Diabetes

Relationship Between Low-Normal Blood Pressure and Kidney Disease in Type 1 Diabetes

Anoop Shankar; Ronald Klein; Barbara E.K. Klein; F. Javier Nieto; Scot E. Moss
From the Department of Community, Occupational, and Family Medicine (A.S.), National University of Singapore, Singapore; and the Departments of Ophthalmology and Visual Sciences (R.K., B.E.K.K., S.E.M.) and Population Health Sciences (F.J.N.), University of Wisconsin, School of Medicine and Public Health, Madison.

Current recommendations, largely based on studies in type 2 diabetes, suggest lower target blood pressures (BPs) for individuals with diabetes than for the general population. However, the effect of lower BP on renal outcomes in type 1 diabetes is uncertain. In a population-based cohort of type 1 diabetes adults (mean age: 33.1 years) based in Wisconsin, of which the distribution of baseline BP was in the low-normal range, we examined the relationship between decreasing categories of systolic and diastolic BP and the 16-year incidence of proteinuria (n=232 of 604) and estimated glomerular filtration rate of <60 mL/min/1.73 m2 (n=158 of 547). Decreasing BP categories had lower relative risk (RR) of developing incident proteinuria (RR comparing decreasing quartiles of systolic BP: 1.00, 0.76, 0.58, 0.73; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.81, 0.66, 0.42; P for trend <0.0001) and incident estimated glomerular filtration rate <60 mL/min/1.73 m2 (RR comparing decreasing quartiles of systolic BP: 1.00, 0.83, 0.61, 0.65; P for trend=0.03; RR comparing decreasing quartiles of diastolic BP: 1.00, 0.84, 0.82, 0.43; P for trend=0.001). These associations were independent of glycemic control and several putative confounding factors. Subjects with either systolic BP <120 mm Hg or diastolic BP <70 mm Hg had significantly lower RR (95% confidence interval) of incident proteinuria (0.63 [0.48 to 0.82]) and incident estimated glomerular filtration rate <60 mL/min/1.73 m2 (0.60 [0.43 to 0.82]); corresponding population-attributable risks for these outcomes were 26.7% and 29.5%, respectively. Our study suggests that lower BP levels, even below the accepted normal range, are protective against kidney disease in adults with type 1 diabetes. Interventional trials are desirable to clarify the clinical significance of this association.

Key Words: type 1 diabetes • blood pressure • chronic kidney disease • GFR • proteinuria • WESDR

Hypertension. 2007;49:48.

© 2007 American Heart Association, Inc.

Obesity: Autonomic Contribution to Blood Pressure

Autonomic Contribution to Blood Pressure and Metabolism in Obesity

Cyndya Shibao; Alfredo Gamboa; Andre Diedrich; Andrew C. Ertl; Kong Y. Chen; Daniel W. Byrne; Ginnie Farley; Sachin Y. Paranjape; Stephen N. Davis; Italo Biaggioni
From the Division of Clinical Pharmacology and the Autonomic Dysfunction Center (C.S., A.G., A.D., G.F., S.Y.P., I.B.) and Divisions of Gastroenterology (K.Y.C.) and Diabetes, Endocrinology, and Metabolism (A.C.E., S.N.D.), Department of Medicine, and the Department of Biostatistics and the General Clinical Research Center (D.W.B.), Vanderbilt University School of Medicine, Nashville, Tenn.

Obesity is associated with alterations in the autonomic nervous system that may contribute to the increase in blood pressure and resting energy expenditure present in this condition. To test this hypothesis, we induced autonomic withdrawal with the ganglionic blocker trimethaphan in 10 lean (32±3 years) and 10 obese (35±3 years) subjects. Systolic blood pressure fell more in obese compared with lean subjects (–17±3 versus –11±1 mm Hg; P=0.019) because of a greater decrease in total peripheral resistance (–310±41 versus 33±78 dynes/sec/cm–5; P=0.002). In contrast, resting energy expenditure decreased less in obese than in lean subjects, (–26±21 versus –86±15 kcal per day adjusted by fat-free mass; P=0.035). We confirmed that the autonomic contribution to blood pressure was greater in obesity after including additional subjects with a wider range of blood pressures. Systolic blood pressure decreased –28±4 mm Hg (95% CI: –38 to –18.0; n=8) in obese hypertensive subjects compared with lean (–9±1 mm Hg; 95% CI: –11 to –6; n=22) or obese normotensive subjects (–14±2 mm Hg; 95% CI: –18 to –10; n=20). After removal of autonomic influences, systolic blood pressure remained higher in obese hypertensive subjects (109±3 versus 98±2 mm Hg in lean and 103±2 mm Hg in obese normotensive subjects; P=0.004) suggesting a role for additional factors in obesity-associated hypertension. In conclusion, sympathetic activation induced by obesity is an important determinant to the blood pressure elevation associated with this condition but is not effective in increasing resting energy expenditure. These results suggest that the sympathetic nervous system could be targeted in the treatment of obesity-associated hypertension.

Key Words: obesity • hypertension • autonomic nervous system • sympathetic nervous system • vascular resistance • metabolism

http://hyper.ahajournals.org/cgi/content/abstract/49/1/27
Hypertension. 2007;49:27.

© 2007 American Heart Association, Inc.

Myogenic tone: basal coronary resistance

Beating myocardium counteracts myogenic tone of coronary microvessels: involvement of ATP-sensitive potassium channels

Satoru Takeda, Tatsuya Komaru, Katsuaki Takahashi, Kouichi Sato, Hiroshi Kanatsuka, Yasunori Kokusho, Kunio Shirato, and Hiroaki Shimokawa
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

Myogenic tone is intrinsic to vascular tissue and plays an important role in determining basal coronary resistance. However, the effect of the beating heart on myogenic tone is unknown. We investigated the effects of myocardium-derived vasoactive factors on the myogenic tone of coronary microvessels in the resting condition and during increased metabolism. Pressurized isolated coronary vessels (detector vessel, DV) of rabbits (n = 33, maximal inner diameter 201 ± 8 µm) were gently placed on beating hearts of anesthetized dogs and observed with an intravital microscope equipped with a floating objective. To shut off the myocardium-derived vasoactive signals, we placed plastic film between DV and the heart. The intravascular pressure was changed from 120 to 60 cmH2O, and pressure-diameter curves were obtained with and without the contact of DV and the myocardium. The direct contact shifted the pressure-diameter curve upward (P <>

coronary microcirculation; vasomotor signals; vasodilation; myocardial metabolism; endothelium

Am J Physiol Heart Circ Physiol 291: H3050-H3057, 2006.

Copyright © 2006 by the American Physiological Society.

Hypercholesterolemia: microvascular levels

Hypercholesterolemia Impairs Transduction of Vasodilator Signals Derived From Ischemic Myocardium
Myocardium-Microvessel Cross-Talk

Kouichi Sato; Tatsuya Komaru; Hiroki Shioiri; Satoru Takeda; Katsuaki Takahashi; Hiroshi Kanatsuka; Masaharu Nakayama; Kunio Shirato
From the Department of Cardiovascular Medicine (K. Sato, T.K., H.S., S.T., K.T., M.N., K. Shirato), Tohoku University Graduate School of Medicine, Sendai, Japan; and the Department of Comprehensive Medicine (H.K.), Tohoku University Hospital, Sendai, Japan.

Objective. Coronary microvessels are functionally coupled to the myocardial metabolic state. In hypercholesterolemia, the coronary vascular dysfunction extends to microvascular levels. We hypothesized that the vasodilator signal transduction from ischemic heart is impaired in the coronary microvascular wall of hypercholesterolemia.

Methods and Results. Rabbits were fed with normal chow (control group) or 2% high-cholesterol diet (hypercholesterolemia group) for 8 weeks. Coronary microvessels isolated from rabbit hearts were pressurized and gently placed on a beating canine heart. Myocardial ischemia was produced in the beating heart and the diameter of the isolated microvessel was observed using an intravital microscope with a floating objective. In control group, the isolated microvessels significantly dilated 2 minutes after the onset of ischemia, and a plateau was observed at 10 minutes. In contrast, the microvessels from hypercholesterolemia group did not dilate during ischemia. Dihydroethidium fluorescence microscopy revealed an elevated superoxide level in the microvessels of hypercholesterolemia group. The application of tiron (free radical scavenger) significantly dilated the isolated microvessels only from hypercholesterolemic animals.

Conclusions. We conclude that the transduction of vasodilator signals derived from ischemic myocardium is impaired in the coronary microvascular wall of hypercholesterolemia. Enhanced oxidative stress in hypercholesterolemia may alter the microvascular function.
We evaluated the cross-talk between the coronary microvessels and the ischemic myocardium by using a novel bioassay method. We elucidated that hypercholesterolemia impairs the transduction of vasodilator signals derived from the ischemic myocardium in the coronary microvascular wall. The impaired cross-talk may underlie the susceptibility to ischemic insults.

Key Words: coronary circulation • hyperlipoproteinemia • ischemia • reactive oxygen species • vasodilation

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2034.
© 2004 American Heart Association, Inc.

Myocardial infarction: Climate study

Climate Impacts on Myocardial infarction deaths in the Athens Territory: the CLIMATE study

P Dilaveris, A Synetos, G Giannopoulos, E Gialafos, A Pantazis and C Stefanadis

The 1-st Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece

Objective: To evaluate the impact of meteorological variables on daily and monthly deaths caused by acute myocardial infarction (AMI).

Methods: All death certificate data from the Athens territory were analysed for AMI deaths in 2001. Daily atmospheric temperature, pressure and relative humidity data were obtained from the National Meteorological Society for Athens for the same year.

Results: The total annual number of deaths caused by AMI was 3126 (1953 men) from a population of 2 664 776 (0.117%). Seasonal variation in deaths was significant, with the average daily AMI deaths in winter being 31.8% higher than in summer (9.89 v 7.35, p < r2 =" 0.109," r2 =" 0.541," p =" 0.004).

Conclusion: Ambient temperature is an important predictor of AMI mortality even in the mild climate of a Mediterranean city like Athens, its effects being predominantly evident in the elderly. Mean monthly humidity is another meteorological factor that appears to affect monthly numbers of AMI deaths. These findings may be useful for healthcare and civil protection planning.

Abbreviations: AMI, acute myocardial infarction; MONICA, MONitoring trends and determinants In CArdiovascular disease; PM, particulate matter

Heart 2006;92:1747-1751

© 2006 by BMJ Publishing Group Ltd & British Cardiovascular Society