82-rubidium positron emission tomography determined myocardial flow reserve and outcomes following cardiac revascularisation - A multicentre registry study.

BACKGROUND: Finding patients with chronic coronary syndromes (CCS) whom revascularization could benefit, is complicated. Myocardial flow reserve (MFR), a measurement of myocardial perfusion, has proven prognostic value on survival and risk of major adverse cardiac events (MACE). We investigated if MFR identifies who may benefit from revascularization. METHODS: Among 7462 patients from Danish hospitals examined with 82Rb PET between January 2018 and August 2020, patients with ≥5% reversible perfusion defects were followed for MACE and all-cause mortality. Associations between revascularisation (within 90 days) and outcomes according to MFR (< and ≥ 2) was assessed by Cox regression adjusted by inverse probability weighting for demographics, cardiovascular risk factors, comorbidities, and 82Rb PET variables. RESULTS: Of 1806 patients with ≥5% reversible perfusion defect, 893 (49%) had MFR < 2 and 491 underwent revascularisation (36.6% in MFR < 2 versus 17.9% MFR ≥ 2, p < 0.001). During a median follow-up of 37.0 [31.0-45.8 IQR] months, 251 experienced a MACE and 173 died. Revascularisation was associated with lower adjusted risk of all-cause mortality (hazard ratio [HR], 0.51 [95% CI, 0.30-0.88], p = 0.015) and MACE (HR, 0.54 [0.33-0.87], p = 0.012) in patients with MFR < 2 but not MFR ≥ 2 for all-cause mortality (HR 1.33 [0.52-3.40], p = 0.542) and MACE (HR 1.50 [0.79-2.84], p = 0.211). MFR significantly modified the association between revascularisation and MACE, but not all-cause mortality (interaction p-value 0.021 and 0.094, respectively). CONCLUSIONS: Revascularization was associated with improved prognosis among patients with impaired MFR. No association was seen in patients with normal MFR. In patients with regional ischemia, MFR may identify patients with a prognostic benefit from revascularization.

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients.

AIMS/HYPOTHESIS: We followed type 2 diabetic patients over a long period to evaluate the predictive value of ambulatory pulse pressure (PP) and decreased nocturnal BP reduction (non-dipping) for nephropathy progression. METHODS: Type 2 diabetic patients (n = 112) were followed for an average of 9.5 (range 0.5-14.5) years. At baseline, all patients underwent 24 h ambulatory BP measurement. Urinary albumin excretion rate was evaluated by three urinary albumin:creatinine ratio measurements at baseline and follow-up. RESULTS: At baseline, patients who subsequently progressed to a more advanced nephropathy stage (n = 35) had reduced diastolic night/day BP variation and higher 24 h systolic BP and PP values; they also had more advanced nephropathy and were more likely to smoke than those with no progression of nephropathy (n = 77). In a Cox regression analysis, independent predictors of nephropathy progression were 24 h PP (p < 0.01), diastolic night:day BP ratio (p = 0.02) and smoking (p = 0.02). The adjusted hazards ratio (95% CI) for each mmHg increment in 24 h PP was 1.04 (1.01-1.07), whereas the adjusted hazards ratio (95% CI) for each 1% increase in diastolic night:day BP ratio was 1.06 (1.01-1.11). Only one of 33 patients (3.0%) with both a diastolic night:day BP ratio and a 24 h PP below the median progressed, whereas 17 of 32 patients (53.1%) with both a diastolic night:day BP ratio and a 24 h PP equal to or above the median progressed to a more advanced nephropathy stage (p < 0.001). CONCLUSIONS/INTERPRETATION: Ambulatory PP, impaired nocturnal BP decline and smoking are strong, independent predictors of nephropathy progression in type 2 diabetic patients.

Ambulatory blood pressure in the transition from normo- to microalbuminuria. A longitudinal study in IDDM patients.

To describe the development in blood pressure (BP) in relation to urinary albumin excretion (UAE) more exactly, 44 initially normoalbuminuric type I diabetic patients and 21 healthy individuals were included in a 3.1-year follow-up study by using ambulatory BP (AMBP) monitoring. Six patients developed microalbuminuria according to accepted criteria (progressors; UAE at follow-up was > 20 micrograms/min). Initial UAE was higher in this group (9.0 x/divided by 1.4 micrograms/min) compared with both the nonprogressors (5.2 x/divided by 1.6 micrograms/min) and the control subjects (3.9 x/divided by 1.6 micrograms/min), P < 0.01. The values were almost identical for initial 24-h AMBP between the progressors and the two other groups. The transition to microalbuminuria (31.7 x/divided by 1.8 micrograms/min) was associated with an increase in 24-h systolic AMBP of 11.5 +/- 8.3 mmHg, which was significantly higher than the increase in the nonprogressors (3.1 +/- 7.7 mmHg) and the control subjects (2.2 +/- 6.1 mmHg, P = 0.02). Significant correlations were detected between development in UAE and development in systolic and diastolic 24-h AMBP (r = 0.39, r = 0.41, P < 0.01). In addition, an increase in UAE, even including increases within the normoalbuminuric range, was always associated with an increase in 24-h AMBP (P < 0.01). Ordinary clinical measurements did not reveal any of these differences or correlations. In conclusion, a close association between increases in UAE and 24-h AMBP emerges in this study. Initial BP was not increased in the progressors.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased QTc dispersion is related to blunted circadian blood pressure variation in normoalbuminuric type 1 diabetic patients.

A reduced nocturnal fall in blood pressure (BP) and increased QT dispersion both predict an increased risk of cardiovascular events in diabetic as well as nondiabetic subjects. The relationship between these two parameters remains unclear. The role of diabetic autonomic neuropathy in both QT dispersion and circadian BP variation has been proposed, but data have been conflicting. The aim of the present study was to describe associations between QT dispersion and circadian BP variation as well as autonomic function in type 1 diabetic patients. In 106 normoalbuminuric (urinary albumin excretion <20 microg/min) normotensive patients, we performed 24-h ambulatory BP (Spacelabs 90207) and short-term (three times in 5 min) power spectral analysis of RR interval oscillations, as well as cardiovascular reflex tests (deep breathing test, postural heart rate, and BP response). No patient had received (or had earlier received) antihypertensive or other medical treatment apart from insulin. In a resting 12-lead electrocardiogram, the QT interval was measured by the tangent method in all leads with well-defined T-waves. The measurement was made by one observer blinded to other data. The QT interval was corrected for heart rate using Bazett's formula. The QTc dispersion was defined as the difference between the maximum and the minimum QTc interval in any of the 12 leads. When comparing patients with QTc dispersion below and above the median (43 ms), the latter had significantly higher night BP (114/67 vs. 109/62 mmHg, P < 0.003/P < 0.001), whereas day BP was comparable (129/81 vs. 127/79 mmHg). Diurnal BP variation was blunted in the group with QTc dispersion >43 ms with significantly higher night/day ratio, both for systolic (88.8 vs. 86.2%, P < 0.01) and diastolic (83.1 vs. 79.5%, P < 0.01) BP. The association between QTc dispersion and diastolic night BP persisted after controlling for potential confounders such as sex, age, duration of diabetes, urinary albumin excretion, and HbA1c. Power spectral analysis suggested an altered sympathovagal balance in patients with QTc dispersion above the median (ratio of low-frequency/high-frequency power: 1.0 vs. 0.85, P < 0.01). In normoalbuminuric type 1 diabetic patients, increased QTc dispersion is associated with reduced nocturnal fall in BP and an altered sympathovagal balance. This coexistence may be operative in the ability of these parameters to predict cardiovascular events.

Blood pressure elevation versus abnormal albuminuria in the genesis and prediction of renal disease in diabetes.

A number of risk factors associated with the development of diabetic nephropathy has been described, such as elevated blood pressure, poor metabolic control, hyperlipidemia, and smoking. Abnormal albuminuria also is associated with progression of renal disease, but has until recently been considered principally a marker of disease activity rather than a risk factor. This article discusses the role of elevated blood pressure versus abnormal albuminuria in a genesis and prediction of renal disease in diabetes. Controversy exists regarding parental disposition to hypertension and early blood pressure elevation in the course of diabetes, but all studies agree that elevated blood pressure--in the presence of abnormal albuminuria--constitutes a risk factor. Because abnormal albuminuria is associated with progression disease, it may itself be a risk factor because increased macromolecular traffic over the glomerular membrane may produce glomerulopathy. Problems related to blood pressure measurement are important, and 24-h recordings of blood pressure may be recommended in some situations. Regarding renal structure, preliminary results suggest that structural lesions precede blood pressure elevation. The solid end point for evaluation of renal disease progression is the fall rate of GFR, with abnormal albuminuria as an intermediate end point, also in drug trials. Abnormal albuminuria may constitute a new indication for antihypertensive treatment, being, as it is, a clear indicator of organ damage, whereas elevated blood pressure with normal AER may not increase risk substantially.

Characteristics and prognosis of normoalbuminuric type 1 diabetic patients.

Intervention in type 1 diabetic patients with increased urinary albumin excretion (UAE) represents a great step forward in modern diabetology. At the moment, the consensus calls for antihypertensive treatment in normotensive type 1 diabetic patients with persistent microalbuminuria. However, recent data indicate that substantial pathophysiological changes have already taken place at the microalbuminuric stage. Thus, prevention of progression from normo- to microalbuminuria would be a major clinical turning point. A considerable number of potential risk factors for progression to microalbuminuria have been proposed, among which are blood pressure elevation and disturbancies in circadian blood pressure variation. We performed 24-h ambulatory blood pressure (AMBP) monitoring in 115 normoalbuminuric (UAE < 20 micrograms/min) patients, along with performing an assessment of circadian blood pressure and heart rate (HR) variation and a short-term power spectral analysis of RR interval oscillations. Patients with UAE above the median had significantly higher systolic and diastolic AMBP compared to the low normoalbuminuric group. The difference in blood pressure between the two groups was most pronounced for the night blood pressure (P < 0.01 and 0.02). A positive correlation between UAE and circadian variation (described as diastolic night/day ratio) was present--that is, the higher the normoalbuminuria, the more blunted the night/day ratio. The patients characterized by a combination of high-normal UAE and blunted circadian variation also proved to have significantly higher HbA1c values, higher 24-h mean arterial blood pressure, and lower vagal activity. In conclusion, high-normal UAE, poor metabolic control, and cigarette smoking are at present the only established risk factors for progression from normo- to microalbuminuria. However, new data emphasizes the close relation between blood pressure and albumin excretion. Pathophysiological abnormalities (poorer glycemic control, higher blood pressure, and attenuated vagal activity) tend to cluster in patients characterized by high-normal UAE and blunted circadian variation of blood pressures, and this patient group might constitute a putative high-risk group.

Effects on blood pressure, glucose, and lipid levels of a high-monounsaturated fat diet compared with a high-carbohydrate diet in NIDDM subjects.

OBJECTIVE: To compare the influence on blood pressure, glucose, and lipid levels of a diet rich in monounsaturated fatty acids with an isocaloric, high-carbohydrate diet in 15 NIDDM subjects. RESEARCH DESIGN AND METHODS: A crossover design with diet interventions and wash-out periods of 3 wk was applied. The patients were randomly assigned to a 3-wk treatment with a high-carbohydrate diet containing 50% of energy as carbohydrate and 30% of energy as fat (10% of energy as monounsaturated fatty acids) or an isocaloric diet with 30% of energy as carbohydrate and 50% of energy as fat (30% of energy as monounsaturated fatty acids). On the last day of the two diets, 24-h ambulatory blood pressure was measured and day profiles of glucose, hormones, and lipids were performed to a test menu rich in carbohydrates. RESULTS: The diet rich in monounsaturated fat reduced daytime systolic (131 +/- 3 vs. 137 +/- 3 mmHg, P < 0.04) and 24-h systolic blood pressure (126 +/- 8 vs. 130 +/- 10 mmHg, P < 0.03) as well as daytime diastolic (78 +/- 2 vs. 84 +/- 2 mmHg, P < 0.02) and diurnal diastolic blood pressure (75 +/- 6 vs. 78 +/- 5 mmHg, P < 0.03) as compared with the high-carbohydrate diet. Evidence of lowered blood glucose levels on the high-monounsaturated diet compared with the high-carbohydrate diet were found with lower fasting blood glucose (6.1 +/- 0.3 vs. 6.8 +/- 0.5 mM, P < 0.05), lower average blood glucose levels (7.4 +/- 0.5 vs. 8.2 +/- 0.6 mM, P < 0.04), and peak blood glucose responses (9.9 +/- 0.6 vs. 11.3 +/- 0.7 mM, P < 0.02). The two diets had the same impact on lipid levels. CONCLUSIONS: A diet rich in monounsaturated fat has beneficial effects on blood pressure and glucose metabolism, whereas no adverse effects on lipid composition in NIDDM subjects is detected.

Renal factors influencing blood pressure threshold and choice of treatment for hypertension in IDDM.

In this article, we analyze the blood pressure (BP) threshold for the start of antihypertensive treatment in insulin-dependent diabetes mellitus (IDDM) patients, with particular emphasis on those with persistent microalbuminuria or proteinuria (incipient and overt nephropathy, respectively). In such individuals, there is a clear increase in the prevalence of hypertension and in actual measured BP values that is not observed in normoalbuminuric patients. In 94 young healthy adults (less than 45 yr of age), average mean +/- SD arterial pressure (MAP; diastolic + 1/3 pulse pressure) was approximately 90.0 +/- 8.1 mmHg, closely corresponding to large population studies. In microalbuminuric IDDM patients, MAP values between approximately 105 and approximately 95 mmHg have been found in different studies, and the level has progressively decreased in various studies between 1984 and 1990 with similar BP-measuring techniques. Somewhat higher values are seen in patients with proteinuria, who are also consistently characterized by reduced glomerular filtration rate (GFR). A clear correlation is found between MAP plotted against the increased rate of microalbuminuria (%/yr) in incipient nephropathy and against fall rate of GFR (ml.min-1.mo-1) in proteinuric patients. In the natural history of renal disease, different cutoff points in MAP for start of progression are observed: greater than 95 mmHg for the start of progression of microalbuminuria and greater than 105 mmHg for the decrease in GFR. During antihypertensive treatment, there is reduction or no progression in microalbuminuria with MAP of approximately 90-95 mmHg and only a limited fall in GFR with MAP of approximately 100 mmHg. However, certain antihypertensive drugs (angiotensin-converting enzyme inhibitors) may have specific renoprotective actions, reducing microalbuminuria at rather low BP levels or even independent of BP reduction. The optimal way of monitoring BP may be by 24-h ambulatory recording.

Albuminuria and 24-h ambulatory blood pressure in normoalbuminuric and microalbuminuric NIDDM patients. A longitudinal study.

OBJECTIVE: To assess the long-term relationships between 24-h ambulatory blood pressure (AMBP), urinary albumin excretion (UAE) rate, and metabolic control in non-insulin-dependent diabetes mellitus (NIDDM) patients with normo- and microalbuminuria. RESEARCH DESIGN AND METHODS: We conducted a prospective study of 23 NIDDM patients (11 with normoalbuminuria and 12 with microalbuminuria) receiving standard clinical care, including antihypertensive treatment, attending the outpatient clinic and 8 healthy control subjects. Twenty-four-hour AMBP and UAE were measured synchronously in addition to fasting plasma glucose, HbA1c, and serum creatinine at baseline and after 4.6 (4.2-5.1) years [mean (range)]. RESULTS: Baseline systolic, but not diastolic, 24-h AMBP was significantly higher in diabetic patients compared with control subjects (146/80 [16/11] vs. 133/78 [9/9] mmHg, P < 0.05), but was similar in normoalbuminuric (143/81 [11/11] mmHg) and microalbuminuric (148/80 [20/10] mmHg) patients during strict blood pressure control. The annual increase in 24-h AMBP was equivalent in diabetic patients (0.6/-0.2 [2.6/1.5] mmHg/year) and control subjects (0.7/0.2 [1.2/1.4] mmHg/year, NS) and not significantly different from zero. Overall UAE did not change in control subjects (5.6 [1.6] vs. 4.4 [1.9]) (geometric mean [antilog SD]) or in the normoalbuminuric (8.7 [1.7] vs. 11.3 [3.0] micrograms/min) and microalbuminuric (35.7 [2.1] vs. 34.5 [3.2] micrograms/min) patients. In diabetic patients, the annual change in UAE correlated significantly with the annual change in the systolic (r = 0.61, P < 0.002) and diastolic (r = 0.54, P < 0.008) 24-h AMBP. In microalbuminuric patients, only the annual increase in systolic 24-h AMBP correlated significantly with the annual change in UAE (r = 0.71, P = 0.010), whereas in the normoalbuminuric patients, only the annual increase in diastolic 24-h AMBP and the annual change in UAE were significantly correlated (r = 0.66, P = 0.026). In a stepwise multiple linear regression analysis, the annual progression in albuminuria in NIDDM patients was significantly determined by increases in systolic (parameter estimate 0.018, SE 0.006, P < 0.008) as well as in diastolic 24-h AMBP (parameter estimate 0.026, SE 0.011, P < 0.033). CONCLUSIONS: In an outpatient clinical setting, 24-h AMBP is similar in NIDDM patients with normo- and microalbuminuria. Alterations in both 24-h AMBP and UAE are on average moderate and equivalent compared with those in healthy control subjects. Although the average change in albuminuria is small, a progression in albuminuria relates to increments in both systolic and diastolic 24-h AMBP.

Determinants of 24-h blood pressure in IDDM patients.

OBJECTIVE: To assess the influence of basic clinical data on ambulatory blood pressure (AMBP) in insulin-dependent diabetes mellitus (IDDM) patients and to evaluate the reproducibility of the method. RESEARCH DESIGN AND METHODS: AMBP was measured in 66 IDDM patients with urinary albumin excretion (UAE) < 20 micrograms/min and in 53 healthy subjects. Determinants of AMBP were identified in a stepwise multiple regression model. In addition, 14 diabetic patients were monitored on two days of the same type, and 14 patients were monitored on one work day and one day off. RESULTS: In healthy subjects, sex was the most important determinant of 24-h blood pressure (BP), whereas UAE and age were the main covariates in diabetes patients. The male-female difference in 24-h diastolic BP (dBP) was 5.6 mmHg lower in diabetic patients than in healthy control subjects (P < 0.05). In patients with long diabetes duration, nighttime dBP (69 +/- 7 mmHg) was higher than in patients with medium diabetes duration (63 +/- 8 mmHg, P < 0.05; after matching for age and sex). Daytime dBP was 5 mmHg higher on a work day than on a day off (P < 0.02). Standard deviation of the difference for repeated measurement of 24-h systolic/diastolic BP in the same subject was 5.7/2.5 mmHg. CONCLUSIONS: The male-female difference in 24-h dBP was attenuated in diabetes. The influence of UAE on AMBP was noticed even in normoalbuminuric diabetic patients. Standardized AMBP was highly reproducible.

Expansion of extracellular volume and suppression of atrial natriuretic peptide after growth hormone administration in normal man.

Sodium retention and symptoms and signs of fluid retention are commonly recorded during GH administration in both GH-deficient patients and normal subjects. Most reports have however, been casuistic or uncontrolled. In a randomized double blind placebo-controlled cross-over study we therefore examined the effect of 14-day GH administration (12 IU sc at 2000 h) on plasma volume, extracellular volume (ECV), atrial natriuretic peptide (ANP), arginine vasopressin, and the renin angiotensin system in eight healthy adult men. A significant GH induced increase in serum insulin growth factor I was observed. GH caused a significant increase in ECV (L): 20.45 +/- 0.45 (GH), 19.53 +/- 0.48 (placebo) (P less than 0.01), whereas plasma volume (L) remained unchanged 3.92 +/- 0.16 (GH), 4.02 +/- 0.13 (placebo). A significant decrease in plasma ANP (pmol/L) after GH administration was observed: 2.28 +/- 0.54 (GH), 3.16 +/- 0.53 (placebo) P less than 0.01. Plasma aldosterone (pmol/L): 129 +/- 14 (GH), 89 +/- 17 (placebo), P = 0.08, and plasma angiotensin II (pmol/L) levels: 18 +/- 12 (GH), 14 +/- 7 (placebo), P = 0.21, were not significantly elevated. No changes in plasma arginine vasopressin occurred (1.86 +/- 0.05 pmol/L vs. 1.90 +/- 0.05, P = 0.33). Serum sodium and blood pressure remained unaffected. Moderate complaints, which could be ascribed to water retention, were recorded in four subjects [periorbital edema (n = 3), acral paraesthesia (n = 2) and light articular pain (n = 1)]. The symptoms were most pronounced after 2-3 days of treatment and diminished at the end of the period. In summary, 14 days of high dose GH administration caused a significant increase in ECV and a significant suppression of ANP.

No deleterious effects of tight blood glucose control on 24-hour ambulatory blood pressure in normoalbuminuric insulin-dependent diabetes mellitus patients.

Intensive therapy aiming at near normalization of glucose levels effectively delays the onset and slows the progression of complications in insulin-dependent diabetes mellitus (IDDM) and is recommended in most patients. However, in a recent report, intensive insulin treatment was found to be associated with deleterious effects on nocturnal blood pressure (BP), the proposed mechanisms being subclinical nocturnal hypoglycemia or hyperinsulinemia. The aim of the present study was to evaluate the association between glycemic control, insulin dose, and 24-h ambulatory BP (AMBP) in a group of well-characterized IDDM patients. Twenty-four-h AMBP was measured in 123 normoalbuminuric [urinary albumin excretion (UAE) < 20 microg/min] IDDM patients using an oscillometric technique (SpaceLabs 90207) with readings at 20-min intervals. UAE was measured by RIA and expressed as geometric mean of three overnight collections made within 1 week. Tobacco use and level of physical activity was assessed by questionnaire. HbA1c was determined by high-pressure liquid chromatography (nondiabetic range, 4.4-6.4%), and patients were stratified into quartiles according to HbA1c levels. Mean HbA1c values in the four groups were 7.0% (n = 31), 8.0% (n = 31), 8.6% (n = 31), and 9.7% (n = 30). The groups were comparable regarding age, gender, diabetes duration, body mass index, UAE, smoking status, and physical activity. AMBP levels were almost identical in the HbA1c quartiles with night values of (increasing HbA1c order): 110/63, 112/66, 112/66, and 113/65 mm Hg (P = 0.69/P = 0.32). There was no association between tight glucose control and higher nocturnal BP or a more blunted circadian BP variation. On the contrary, a weak positive correlation between night to day ratios of mean arterial BP and HbA1c values was found (r = 0.26, P = 0.005), i.e. blunted circadian BP variation is most frequent in patients with high HbA1c values. Neither did we find doses of insulin to be associated with night BP (r = 0.04, P = 0.68). Tight blood glucose control is not associated with deleterious effects on 24-h AMBP in normoalbuminuric IDDM patients. Intensive therapy can be implemented without concerns of inducing high nocturnal BP and accelerating diabetic complications.

A plea for consistent reliability in ambulatory blood pressure monitors: a reminder.

OBJECTIVE: To compare three different software versions [read-only memory (ROM) versions 1.22, 1.24 and 1.28] of the SpaceLabs model 90202 ambulatory blood pressure monitor. DESIGN: Simultaneous measurements in a two-arm crossover design. METHODS: Ten measurements each in 14 normotensive persons were performed to compare each pair of monitors. The results were corrected according to the deviation from a mercury column. The systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP) was noted and the factor K = (MAP - DBP)/(SBP - DBP) was calculated. RESULTS: The K factor in the two older ROM versions was close to 0.25, with no statistically significant difference. In contrast the K factor was higher in the most recent ROM version than in one of the previous versions. This could be explained by a 5.4 mmHg increase in MAP found by the new version. A significant difference in blood pressure was observed even between two monitors with the same ROM version. CONCLUSION: Unnotified changes in the software version in the SpaceLabs 90202 monitor operating by an oscillometric technique seriously affect the reliability of MAP measurements. Whenever possible in clinical trials the same monitor should be used for the same patient on each occasion. The industry should inform clinicians of the consequences of updating apparently identical monitors.

Effects of smoking on 24-h ambulatory blood pressure and autonomic function in normoalbuminuric insulin-dependent diabetes mellitus patients.

Smoking is an important risk factor for the development and progression of diabetic nephropathy. The mechanisms by which smoking increases albuminuria and promotes nephropathy are unknown. Considering the acute pressor effect of smoking and the close association between blood pressure elevation and development of diabetic nephropathy, blood pressure increase might be implicated in the association between smoking and diabetic nephropathy. However, among nondiabetics, smokers have repeatedly been found to have lower blood pressure than nonsmokers. This is possibly mediated by an autonomic adjustment to sustained sympathetic stimulation by nicotine. Impaired modulation of the sympathovagal activity has been described in diabetes. In diabetic patients, the effect of smoking on blood pressure and autonomic function remains unclarified. We examined 24-h ambulatory blood pressure (oscillometric technique) and autonomic function (short-term power spectral analysis as well as conventional tests) in 24 smokers and 24 nonsmokers matched for sex, age, and diabetes duration. All patients were normoalbuminuric insulin-dependent diabetes mellitus patients. Smoking status was assessed by questionnaire with confirmatory determinations of urinary cotinine. Diabetic smokers had significantly higher 24-h mean arterial blood pressure (94+/-6.7 mm Hg compared to diabetic nonsmokers 90+/-5.8 mm Hg, P = .04) including higher diastolic nighttime blood pressure (68+/-7.3 mm Hg v 64+/-5.2 mm Hg, P = .03). Smokers also had significantly higher 24-h heart rate (80+/-7.2 compared to 72+/-9.2 beats/min, P < .001). In addition, smoking was associated with significantly reduced short-term RR interval variability (supine low frequency component) (5.45+/-1.29 ln ms2 in smokers compared to 6.31+/-1.11 ln ms2 in nonsmokers, P < .02), as well as reduced brake index (33.5+/-14.5 in smokers v 42.1+/-16.0 in nonsmokers, P < .05). Diabetic smokers have significantly higher 24-h blood pressure compared to diabetic nonsmokers. This finding, contrasting the effect of smoking among nondiabetics, is possibly mediated by coexisting abnormal postural responses in autonomic cardiac regulation in diabetic smokers. Blood pressure elevation, persisting throughout 24 h, might be operative in the association between smoking and development of diabetic nephropathy.

Ambulatory blood pressure and abnormal albuminuria in type 1 diabetic patients.

In healthy individuals compared to normoalbuminuric patients, day time blood pressure (BP) is indistinguishable between the groups in most studies, while a slightly higher nocturnal systolic BP is a common finding. Despite a comparable clinic BP both day and night BP are higher in microalbuminuric patients, and the diastolic night/day ratio is clearly elevated as compared with healthy controls. In normo- and microalbuminuric patients ambulatory blood pressure (AMBP) correlates with urinary albumin excretion (UAE). The evolution of AMBP in a three year follow-up study presented evidence that in healthy individuals the increase in 24 hour systolic BP was approximately 1 mm Hg per year and was almost identical to the increase in persistent normoalbuminuric patients. In contrast, patients who progressed to microalbuminuria exhibited a fourfold higher increase in 24 hour AMBP compared to the persistent normoalbuminuric patients. Ordinary clinic measurements did not reveal this difference. There was no difference in initial 24 hour AMBP in progressors and non-progressors. Our study favors the concept of a simultaneous rise in BP and UAE. In overt renal disease, AMBP is significantly higher than in microalbuminuric patients. The circadian variation of blood pressure is blunted particularly in patients with advanced diabetic nephropathy and antihypertensive treatment. AMBP in type 1 diabetic patients allows: (1) the detection of minor but clinical relevant elevations of BP; (2) to disclose and association between BP and UAE in cross sectional studies; (3) to give a description of the blunted diurnal BP rhythm in patients with incipient or overt diabetic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

High normo- or low microalbuminuria: basis for intervention in insulin-dependent diabetes mellitus.

Recent studies have further elucidated the association between blood pressure and albumin excretion in insulin-dependent diabetes mellitus (IDDM) patients with (i) normal urinary albumin excretion (UAE), and (ii) moderate microalbuminuria (20 to 70 micrograms/min). In a study comprising 117 normoalbuminuric (UAE < 20 micrograms/min) patients we performed 24-hour ambulatory blood pressure monitoring (AMBP), and short-term power spectral analysis of RR interval oscillations. In comparison with the group with a UAE below the median, patients with UAE above the median were characterized by: significantly higher 24-hour systolic and diastolic AMBP, significantly reduced short-term RR interval variability, and significantly higher HbA1c. In a double blind study, normotensive IDDM patients with moderate microalbuminuria (20 to 70 micrograms/min) were randomized to either lisinopril (20 mg once a day, N = 12) or placebo (N = 10) for two years. In the lisinopril group there were significant reductions in 24-hour systolic and diastolic AMBP compared to the placebo group. Lisinopril did not attenuate the diurnal blood pressure variation. UAE tended to be reduced in the lisinopril group. A significantly positive association between changes in AMBP and changes in UAE was present in the placebo group in contrast to the lisinopril group. Changes in UAE were strongly and positively associated with changes in filtration fraction in the lisinopril treated group. In conclusion, interactions between albumin excretion, blood pressure, autonomic function, and glycemic status are already detectable within the normoalbuminuric range in IDDM patients. Angiotensin converting enzyme inhibitor (ACEi) treatment in a small group of normotensive IDDM patients with moderate microalbuminuria reduces blood pressure without attenuating diurnal blood pressure variation, tends to reduce albumin excretion, and abolishes the association between changes in UAE and changes in blood pressure observed in the placebo group. ACEi intervention in selected normoalbuminuric high risk patients (high-normal UAE, high-normal blood pressure, and poor glycemic control) would be of interest.

24-h blood pressure recordings in type I diabetic patients.

Ambulatory blood pressure (AMBP) is of particular interest in diabetes because of the close association between elevated BP and diabetic nephropathy and the attenuated night drop in some diabetic subgroups: (1) Normoalbuminuric patients: If standardized for type of day (work or day off), coefficient of variation (CV) for 24 h AMBP is 2%-3% and 5%-6% for night/day ratio. The male-female difference in AMBP seen in healthy subjects is reduced in diabetes. Smoking did not significantly affect AMBP. AMBP is increased in patents with high normal urinary albumin excretion (UAE). Night/day ratio of AMBP and night heart rate is higher in long than short term diabetic patients. This difference in night/day ratio is not significant if the slightly higher UAE in long-term patients is accounted for. (2) Microalbuminuric patients: Diastolic night/day ratio is increased compared with healthy controls, with the value for normoalbuminuric patients in between. A large overlap between groups is evident. Thus the prognostic value of a single abnormal night/day ratio is doubtful. If divided into dippers and nondippers, no difference in extracellular- or plasma volume is found, but nondippers have a lower plasma aldosterone and arginine vasopressin level, possibly to counteract volume expansion. (3) Patients with overt nephropathy: A marked increased in AMBP and a clear reduction of the nocturnal blood pressure fall is seen. In conclusion, AMBP (but not night/day ratio) is highly reproducible. The association between elevated AMBP, elevated night/day ratio, and pathological UAE is detectable even in normoalbuminuric patients. The prognostic importance of abnormal circadian variation of BP is unsettled.

Acute renal effects of angiotensin converting enzyme inhibition in microalbuminuric type 1 diabetic patients.

The renal effects of intravenous injection of 10 mg enalapril were investigated in 16 normotensive microalbuminuric type 1 (insulin-dependent) diabetic patients. After enalapril the following changes were observed: fractional albumin clearance (theta Alb) decreased from 9.9 (3.0-23.8) to 8.2 (2.0-18.3) x 10(-6) (2 P < 0.01); filtration fraction (FF) decreased from 0.260 (0.225-0.312) to 0.253 (0.190-0.297) (2 P < 0.01); renal plasma flow (RPF) increased from 565 (411-690) to 623 (449-785) (2 P < 0.01); and glomerular filtration rate (GFR) remained stable at 149 (128-181) versus 150 (124-185) ml.min-1 (NS). These values were unchanged after placebo (n = 8), except for RFP which decreased from 606 (401-701) to 559 (381-677) ml.min-1 (2 P < 0.05) and GFR which was reduced from 148 (111-173) to 138 (111-167) (2 P < 0.05). A reduction in mean blood pressure from 94 (87-103) to 89 (79-101) mmHg (2 P < 0.05) was found in the enalapril group and a minor reduction in the placebo group from 97 (83-106) to 96 (81-104) mmHg (2 P < 0.05) was also noted. The relative changes in systolic blood pressure in the enalapril group correlated with changes in theta Alb (Spearman's r = 0.66, 2 P < 0.02) and FF (r = 0.53, 2 P < 0.05). Acute inhibition of angiotensin converting enzyme does not reduce the pathological hyperfiltration in these patients and a reduction in theta Alb and FF can not be dissociated from the reduction in blood pressure.

[Favourable effect of olive oil in patients with non-insulin-dependent diabetes. The effect on blood pressure, blood glucose and lipid levels of a high-fat diet rich in monounsaturated fat compared with a carbohydrate-rich diet]. / Gunstig virkning af olivenolie hos ikkeinsulinkraevende diabetikere. Virkningen på blodtryk, blodglukose og lipidniveauer af en dioet med et højt indhold af monoumoettet fedt sammenlignet med en kulhydratrig dioet.

To compare blood pressure, glucose and fat metabolism after a high-fat diet rich in monounsaturated fat reduced day time systolic (131 +/- 3 vs. 137 +/- 3 mmHg, p < 0.04) and 24-hour systolic blood pressure (126 +/- 8 vs. 130 +/- 10 mmHg, p < 0.03) as well as day time diastolic (78 +/- 2 vs. 84 +/- 52 mmHg, p < 0.02) and diurnal diastolic blood pressure (75 +/- 6 vs. 78 +/- 5 mmHg, p < 0.03) as compared with the high-carbohydrate diet. Evidence of improved glucose tolerance on the high-monounsaturated diet compared with the high-carbohydrate diet were found with lower fasting blood glucose (6.1 +/- 0.3 vs. 6.8 +/- 0.5 mM, p < 0.05), lower average blood glucose levels (7.4 +/- 0.5 vs. 8.2 +/- 0.6 mmol/l, p < 0.01) and peak blood glucose responses (9.9 +/- 0.6 vs. 11.3 +/- 0.7 mmol/l, p < 0.02). Similar levels of fasting triglyceride, total cholesterol, LDL- and HDL cholesterol were found after the two diets.

Micro-albuminuria and the organ-damage concept in antihypertensive therapy for patients with insulin-dependent diabetes mellitus.

OBJECT OF TREATMENT: Antihypertensive treatment in hypertensive patients with insulin-dependent diabetes mellitus is intended to prevent long-term complications, particularly diabetic nephropathy. DIABETIC HYPERTENSIVES WITH ABNORMAL ALBUMINURIA: Antihypertensive therapy, particularly with angiotensin converting enzyme (ACE) inhibitors, typically produces a permanent reduction in the decline of the glomerular filtration rate (GFR) in diabetic patients with abnormal albuminuria. The rate of decline in the GFR during antihypertensive treatment is a well accepted end-point in diabetic renal disease. DIABETIC HYPERTENSIVES WITHOUT ABNORMAL ALBUMINURIA: In insulin-dependent diabetic patients with essential hypertension but with normal urinary albumin excretion there is no reduction in the GFR. Longitudinal studies have shown a fall in the GFR only in the presence of significantly increased urinary albumin excretion. ABNORMAL ALBUMINURIA AS A MARKER OF INCIPIENT NEPHROPATHY: Micro-albuminuria and proteinuria may be pathogenetic factors in the development of nephropathy, leading eventually to end-stage renal failure in diabetic patients. Measurements of micro-albuminuria and proteinuria, in addition to blood pressure recordings, might therefore be used as indications for initiating antihypertensive treatment. NEED TO MONITOR PATIENTS FOR ABNORMAL ALBUMINURIA: Transglomerular macromolecular traffic may produce mesangial damage, with subsequent glomerulopathy and diabetic nephropathy. Thus, close monitoring for micro-albuminuria and proteinuria is desirable in the management of diabetic hypertensive patients.