Vascular risk factors correlate to the extent as well as the severity of coronary atherosclerosis.

BACKGROUND: Because most acute coronary events result from thrombosis at sites of minor plaque, the extent of non-obstructive coronary artery disease (CAD), rather than simply the number of severe stenoses, might be clinically relevant. OBJECTIVE: To examine the relationship between vascular risk factors and a novel extent score for CAD that measures the percentage of the coronary tree involved with atheromatous plaque, as judged by coronary angiography. METHODS: We assessed the extent and severity of CAD and the presence of vascular risk factors of 429 consecutive eligible patients (296 men, aged 61 +/- 11 years) who presented for elective coronary angiography. Detailed analyses of lipid levels were performed for 126 subjects. RESULTS: The mean extent score was 54 (range 0-100). The presence of diabetes (P < 0.001), current or former smoking (P < 0.005) and a history of hypertension (P < 0.001) were all strongly associated with the CAD extent score, as was severity of disease. For the 283 patients with one or no severe stenosis, diabetes was associated with a greater extent score (57 versus 41%, P < 0.005), as was smoking (49 versus 34%, P < 0.005). For the 126 patients with detailed data on lipid levels, extent of coronary artery disease was independently correlated to age (P < 0.005), male sex (P < 0.05), presence of diabetes (P < 0.05), hypertension (P < 0.05), level of lipoprotein (a) (P < 0.005) and low-density:high-density lipoprotein ratio (P < 0.01) in multivariable analysis. CONCLUSIONS: Extent of CAD, as well as its severity, is significantly associated with traditional vascular risk factors. Because most acute coronary events occur at sites of minor plaque, this might explain the mechanism whereby risk factors confer adverse prognostic significance.

Does insulin therapy have a hypertensive effect in type 2 diabetes?

In this prospective study, the 24-h blood-pressure profile of 12 patients with type 2 diabetes was monitored before, at 6, and at 12 weeks after initiation of insulin therapy, to determine whether commencement of insulin therapy increases blood pressure in these patients. Insulin dosage adjustment was carried out by using a predetermined algorithm according to body weight and degree of hyperglycemia. The mean insulin dosage at 12 weeks was 72.9 +/- 3.9 units/day. This was associated with an increase in systolic blood pressure from 134.6 +/- 4.3 mm Hg to 144.8 +/- 4.5 mm Hg (p = 0.0001), diastolic blood pressure from 71.9 +/- 2.6 mm Hg to 74.9 +/- 2.2 mm Hg (p = 0.0001), and body mass index (BMI) from 27.2 +/- 0.8 kg/m2 to 29.6 +/- 0.8 kg/m2 (p = 0.0001). Multiple regression analysis showed insulin dosage to be a significant independent factor (p = 0.0003) accounting for 63% of the variance in blood pressure change after adjusting for age, diastolic blood pressure, and base HbA1c. We conclude that insulin therapy may have a deleterious effect on blood pressure in patients with type 2 diabetes. However, in the clinical setting, it is difficult to isolate this from the confounding effect of weight gain.

Felodipine in combination with a beta-adrenoceptor blocker as an effective substitute for triple therapy in severe hypertension. The Australian Felodipine Multicentre Study Group.

We have studied the efficacy and tolerability of felodipine plus a beta-adrenoceptor blocker in 79 patients with essential hypertension previously treated with a combination of three or more anti-hypertensive agents, one of which was a beta-adrenoceptor blocker. After a 4-week run-in period on the same beta-blocker plus placebo (as a substitute for the other agents in the regimen), felodipine was added and its dose titrated to achieve a supine diastolic blood pressure or less than 90 mm Hg. This was followed by a 12-week maintenance phase in all patients, and 47 patients entered an optional long-term follow-up for an additional 9 months. The mean supine blood pressure was 149/88 mm Hg at entry and 174/108 mm Hg after the run-in phase. Felodipine significantly reduced the blood pressure to 142/85 mm Hg after dose titration and to 141/84 mm Hg after 12 weeks, 94% of patients achieving a supine diastolic blood pressure of 90 mm Hg or below. This reduction was maintained in the patients who were followed for 12 months. The adverse events recorded were usually mild, transient, and typical for an effective precapillary vasodilator. Nine of 74 patients (11%) were withdrawn in the first phase of the study because of adverse events and 5 of 47 patients were withdrawn during the long-term follow-up. These results show that the efficacy and tolerability of a combination of felodipine with a beta-blocker allow a simplified regimen for hypertensive patients who were previously taking three or more drugs for satisfactory blood pressure control.

Thin-membrane nephropathy--a common cause of glomerular haematuria.

Thin-membrane nephropathy recently has been described as a cause of glomerular haematuria. The prognosis of the condition is unclear but it generally is considered to be benign. In a series of 92 patients with glomerular haematuria, thin-membrane nephropathy was found to be a common cause, occurring in 26 (28%) patients. Sixteen patients were women. The mean age was 42 years. Four patients had a family history of renal disease or haematuria and no patient was deaf. Haematuria had been present from six days to 30 years. Loin pain occurred in 31% of patients. Hypertension was not a feature and mild renal impairment was present in one case only, while a further three cases showed proteinuria at a level of greater than 500 mg of protein per day. Glomerular basement membranes in patients with thin-membrane nephropathy gave a mean (+/- standard deviation) width of 319 + 37 nm which was significantly (P less than 0.002) less than the control value of 394 +/- 61 nm. On the basis of clinical features and serological parameters, thin-membrane nephropathy could not be separated from other renal causes of haematuria but required careful electronmicroscopic examination of renal biopsy material to establish the diagnosis. Limited follow-up has confirmed the good prognosis of the condition.

Fibrillary glomerulonephritis--a report of two cases.

Two patients with an uncommon form of glomerulonephritis are described. The main clinical features were hematuria and proteinuria associated with normal renal function. The glomerular lesions consisted of mesangial hypercellularity and capillary wall thickening. Immunofluorescence was positive for IgG and C3 in both cases. Widespread deposition of microfibrils (mean diameters 17.0 nm and 18.4 nm) within mesangial areas and capillary basement membranes was seen on electron microscopy. Congo red staining for amyloid was negative. In both patients there was no evidence of underlying disease or extra-glomerular involvement and hence the disorder appeared to represent a primary glomerulonephritis.

Influence of renin levels on the treatment of essential hypertension with thiazide diuretics.

Initial plasma renin activity (PRA) was measured in 213 patients with untreated hypertension before beginning thiazide (chlorothiazide and hydrochlorothiazide) therapy alone to test whether patients with low-renin hypertension exhibited a greater response to diuretic therapy. Diastolic blood pressure response to treatment in the low, mid-range, and high PRA groups did not differ significantly (delta diastolic blood pressure, -13.6 +/- 1.6, -11.6 +/- 1.5, and -10.8 +/- 2.6 mm Hg, respectively). Moreover, eight subjects with the highest PRA values exhibited the same magnitude of decrease in diastolic blood pressure as did the low PRA group (15.0 +/- 4.2 vs 13.6 +/- 1.6, respectively). This study thus provides no evidence for increased sensitivity to diuretic therapy among patients with low-renin essential hypertension.