Gianni Carzaniga

Basal nitric oxide production is not reduced in patients with noninsulin-dependent diabetes mellitus

Vascular disease is the leading cause of morbidity, disability and death in patients with noninsulin-dependent diabetes mellitus. Abnormalities in endothelium-derived nitric oxide (NO) have been demonstrated to be involved in the pathogenesis of vascular disease. By measuring hemodynamic responses to a NO synthase agonist or antagonist, previous studies have shown the presence of NO deficiency in patients with noninsulin-dependent diabetes mellitus, a method of assessing bioactive NO formation. However, direct biochemical evidence that this is the case, has not been produced. In vivo NO is metabolized into nitrate, an end breakdown product of NO, which can be used as an index of endogenous NO formation. To investigate further whether decreased basal synthesis of NO may be a major cause of endothelium-mediated vascular dysfunction in patients with noninsulin-dependent diabetes mellitus, the plasma nitrite/nitrate levels of 15 patients were examined and compared with 13 normal controls. The results showed that in basal conditions plasma nitrite/nitrate levels were not reduced in diabetic patients compared with normal controls (37.3 ± 14.7 versus 29.4 ± 8.6 μmol/l). It was concluded that in noninsulin-dependent diabetes mellitus patients, endothelium-derived basal NO formation is not impaired. This study, taken with previous observations, suggests that factors other than diminished basal NO production, such as reduced bioavailability of NO probably due to the augmented production of superoxide anion with subsequently increased inactivation of NO, contribute to the high incidence of vascular disease in patients with noninsulin-dependent diabetes mellitus.

Lp(a) in hypertensive patients

Lipoprotein(a) (Lp(a)) is considered an important risk factor for coronary disease, cerebrovascular pathology and re-stenosis of coronary bypass. Few studies have been conducted on this lipoprotein in essential arterial hypternsive patients. The purpose of our study was to measure the serum concentrations of Lp(a) and the main parameters of the lipid profile in a group of essential hypertensive patients not receiving pharmacological treatment and with no clinical signs of associated pathologies or organ damage. A total of 123 Caucasian essential arterial hypertensive patients (47 men and 76 women) were studied and compared with 89 controls (36 men and 53 women) matched in terms of age, sex, body mass index (BMI) and smoking habits. It was found that the hypertensive patients had higher plasma concentrations of Lp(a), total cholesterol (TC), triglycerides (TG) and very low density lipoprotein (VLDL-C) than controls (P < 0.01), with no differences in the plasma concentrations of lp(a) between the two sexes. only 10 hypertension patients and seven controls had plasma concentrations of lp(a) of over 30 mg/dl. lp(a) does not correlate with the main parameters of the lipid profile. we can confirm that hypertension and dyslipidaemia, which are two of the main risk factors for vascular diseases on an atherosclerotic basis, are often associated. however, higher plasma concentrations of lp(a), albeit within the normal range, could be an independent risk factor for atherosclerosis, and could contribute towards increasing the incidence of cardiovascular disease in people with essential arterial hypertension.

Reply to Arterial Stiffness in Patients With Peripheral Arterial Disease

To the Editor: Many thanks to Balta and colleagues for the appreciation of our work “Increased Aortic Stiffness and Related Factors in Patients With Peripheral Arterial Disease” recently published in The Journal of Clinical Hypertension. However, we disagree on some remarks made by the same authors. We did not mention the effects of heart failure and inflammatory disease such as psoriasis on aortic stiffness. Neither of these conditions were included in our analysis because the patients did not present these symptoms at the time of enrollment in the study. In addition, it would be more interesting to conduct a study in patients without atherosclerosis disease, diabetes, or hypertension to clarify the relationship between alcohol intake and aortic stiffness. In the discussion, we mention the lack of relationship between the common risk factors (smoking and diabetes) and aortic pulse wave velocity (aPWV) illustrating the results (in Table 2) on the main determinants of aPWV (age, heart rate, blood pressure) leaving out, however, the lack of relationship between smoking (b=0.56, P=.31), dyslipidemia (b=0.82, P=.08), low-density lipoprotein (b=0.008, P=.19), cerebrovascular disease (b=2.87, P=.12), and aortic stiffness. These results are in agreement with the findings of a recent systematic review of the literature concerning aPWV and cardiovascular risk factors. In particular, Cecelja and Chowienczyk identified several studies with data relating aPWV to age, blood pressure, and a variable number of other cardiovascular risk factors, in which regression models were available. The results from this review demonstrate that only age and blood pressure are consistently related to aPWV. Other risk factors were no longer significant after adjusting for age and blood pressure, suggesting that the impact of traditional risk factors, other than BP, on aPWV is small or insignificant. Furthermore, atherosclerosis risk factors, per se, appear to play a minor role in aortic stiffening as highlighted by McEniery and colleagues. Finally, we report that the regression model could only predict a part of the variability of aPWV (R=11; 8%, P=.01) indicating that markers of inflammation and/or vascular calcification associated with PAD, not currently studied in our paper, may play an important role in aortic stiffness. Arteriosclerosis and atherosclerosis are two processes pathologically distinct and largely driven by different mechanisms.

Increased Aortic Stiffness and Related Factors in Patients With Peripheral Arterial Disease

A number of conditions have been associated with functional changes of large arteries. The aim of this study was to evaluate the factors associated with aortic stiffness in patients with peripheral arterial disease (PAD). The authors studied 86 patients with PAD (ankle‐brachial pressure index [ABPI] ≤0.9) and 86 controls. Aortic stiffness was determined by pulse wave velocity (aPWV) using applanation tonometry. In PAD patients, aPWV was higher compared with controls (11±3 vs 9.8±1.8; P=.002). In multiple regression analysis, aPWV was independently associated with pulse pressure (β=0.05, P=.01) in the PAD patients and with age in the control group (β=0.08, P=.0005). The results of this study confirm an aPWV increase in patients with PAD and emphasize the association between blood pressure and aPWV. Further studies are necessary to assess whether higher aortic stiffening adds prognostic value to ABPI, which is the most powerful prognostic indicator in PAD.

Aortic augmentation index in patients with peripheral arterial disease.

Aortic augmentation index (AIx) is used to investigate arterial stiffness. The authors tested the hypothesis that patients with peripheral arterial disease (PAD) demonstrate a higher AIx and also evaluated several related factors. In 97 patients with PAD, identified by ankle‐brachial pressure index (ABPI ≤0.9), and 97 controls (ABPI ≥0.91<1.4), AIx (%) was determined using tonometry of the radial artery. There was no significant difference between patients and controls in characteristics of age, sex, height, diastolic blood pressure, mean blood pressure, and heart rate. AIx was higher in patients with PAD (32±9 vs 28±9; P=.001). In multivariate regression analysis, AIx was independently associated with heart rate (β=−0.40, P=.0005). This study showed that AIx increased in patients with PAD and that heart rate is a determinant of AIx. Further studies are necessary to assess the pathophysiological and clinical importance of AIx in patients with PAD.

Effects of treatment with verapamil SR and captopril on the lipid profile of hypertensive patients

SummaryThe potential beneficial effects of antihypertensive drugs on cardiovascular morbidity and mortality may be compromised by their adverse effects on serum lipid levels. In our study we compared verapamil and captopril and evaluated their effects on blood pressure and on serum lipid and lipoprotein levels, with particular attention to lipoprotein(a) [Lp(a)].20 hypertensive patients were treated with sustained release verapamil 240mg once daily or captopril 25mg twice daily for 3 months in a double-blind randomised study. Diastolic blood pressure was reduced from 100 ± 3mm Hg to 87 ± 6mm Hg (p < 0.01) and from 100 ± 5mm Hg to 92 ± 7mm Hg (p < 0.05) in the verapamil and captopril groups, respectively. Small but significant changes in serum lipid levels were noted: total cholesterol was reduced from 6 to 5.8 mmol/L (verapamil) and from 6.1 to 5.9 mmol/L (captopril); low density lipoprotein (LDL) cholesterol was reduced from 4 to 3.8 mmol/L (verapamil) and from 4.2 to 3.9 mmol/L (captopril); apolipoprotein C-III was reduced from 0.3 ± 0.07 to 0.2 ± 0.06 mmol/L (9.7 ± 2.5 to 9.2 ± 2.3 mg/dl) [verapamil] and from 0.2 ± 0.1 to 0.2 ± 0.09 mmol/L (9.1 ± 3.7 to 8.3 ±3.4 mg/dl) [captopril]; apolipoprotein A-II increased only with verapamil (p < 0.02). Lp(a) levels showed only minor changes in individual patients.In conclusion, in our study verapamil and captopril were effective antihypertensive agents and did not adversely effect the lipid profile.

Elastic properties and structure of the radial artery in patients with type 2 diabetes

Alterations of elastic properties may contribute to the accelerated atherosclerosis in patients with T2D. Little is known, however, about radial artery distensibility in this patient group. A total of 19 patients with T2D and 19 controls were investigated.An echotracking system coupled to a plethysmograph was used to assess the morphologic and elastic properties of radial artery. Distensibility and compliance were evaluated using Langewouters’ equations. Distensibility and compliance did not differ significantly in patients with diabetes compared with controls. In contrast, radial IMT and WCSA were significantly higher in patients with T2D than in controls. Multiple regression analyses revealed a significant association between SBP and IMT (r 2 = 0.40, p<0.001) as well as WCSA (r = 0.54; r 2 = 0.30; p<0.001 ) in individuals with diabetes. In conclusion, distensibility and compliance of the radial artery are not reduced in patients with T2D. In contrast, radial IMT and WCSA are significantly higher in patients with T2D than in controls.These modifications are chiefly and positively related to SBP.

Impact of Mild hypertriglyceridemia on fibrinolysis, Lp(a), and platelet activation indexes in mildly hypercholesterolemic patients

The relationship between high triglyceride values and alterations of the fibrinolytic system in cardiovascular heart disease (CHD) patients is well known. The aim of the study was to evaluate the effect of moderate hypertriglyceridemia on fibrinolysis, lipoprotein(a) [(Lp(a)], and platelet activation indexes in asymptomatic patients. To this end, 46 nondiabetic, dyslipidemic patients (age 51±8 years), with no associated pathologies and 23 normolipidemic, homogeneus patients (in terms of age, sex, and smoke habits) were studied. The dyslipidemic patients were split up into two groups: 23 type IIb hyperlipoproteinemia patients (Group I), and 23 type IIa hyperlipoproteinemia patients (Group 2). The control group had total cholesterol values of <5.18 mmol/L and triglyceride concentrations of <2.25 mmol/L. The result showed a significant difference (p<0.05) in the baseline plasminogen tissue activator inhibitor (PAI-1 b) values for the Group 1 patients as compared with the Group 2 and the controls, in the baseline tissue plasminogen activator (t-PA b) values for the Group 1 patients as compared with the Group 2 patients and in the lipoprotein (a) (Lp(a)) (p<0.01) values for the Group 2 as compared with the controls. On the other hand, no statistically significant difference was observed in β-thromboglobulin (β-TG), platelet factor 4 (PF4). This study shows that mild hypertriglyceridemia in asymptomatic hypercholesterolemic patients is associated with a different regulation of the fibrinolytic mechanism. In patients with moderate hypercholesterolemia, higher blood concentrations of Lp(a) were found than in the controls.

Arterial stiffness and subendocardial viability ratio in patients with peripheral arterial disease

Arterial stiffening is a hallmark of the aging process and atherosclerosis, including peripheral arterial disease (PAD). We investigated the associations between carotid‐femoral pulse wave velocity (c‐fPWV), augmentation index corrected for heart rate (Aix@HR75), ankle brachial index (ABI), and subendocardial viability ratio (SEVR), an indicator of cardiac perfusion. The c‐fPWV, Aix@HR75, and SEVR was estimated using applanation tonometry. The ankle systolic pressure measurements for the calculation of the ABI were obtained using an 8‐mHz Doppler probe. The study group included 555 subjects, mean age 63 ± 11 years (248 PAD (ABI < 1.0), and 307 non‐PAD (ABI ≥ 1.0 ≤ 1.3). After the stepwise selection process in both PAD and non‐PAD patients SEVR was not related to c‐fPWV and ABI (P = .154; P = .156) and (P = .101; P = .402), respectively. In PAD patients, SEVR was negatively related to Aix@HR75 (P < .0001) and aortic PP (P = .0005). In conclusion, arterial stiffness is associated with non‐invasive indices of myocardial perfusion in PAD patients, suggesting a potential pathophysiological link for increased cardiovascular events.

Arterial Damage, Triglycerides, Apolipoprotein, and Lp-(a) Values in PVD Patients

The aim of the study was to provide a detailed apolipoproteic profile in stage II peripheral vascular disease (PVD) patients and to ascertain whether lower ankle/ arm pressure index (API) values were associated with a worse profile. Apolipoproteins of 83 stage II PVD patients (average age 64.7 ± 9.3 years) were selected and compared with those of a group of 44 normal control subjects, similar in terms of age, sex, and smoking and eating habits. Neither PVD patients nor controls had ever received lipid-lowering agents or defined dietary treatment. A diagnosis of PVD was confirmed by an API of <0.85. Arteriopathic patients were also split into two groups, depending on their API values, similar in terms of age, sex and smoking habits: API values of one group (n = 38) were ≥0.6, those of the other group (n = 45) were <0.6. The following biohumoral parameters were considered: fasting glycemia, total cholesterol, triglycerides (TGs); high-density lipoprotein cholesterol (HDL-C); low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), total cholesterol (TC)/HDL-C (TC/ HDL-C), Apoproteins (Apos) AI, AII, B, CII, CIII, and E; and lipoprotein a [Lp(a)]. HDL-C and Apo AI were lower (p < 0.01), while TC/ HDL-C ratios, Apo B, and Apo CII were higher (p < 0.01) in PVD patients compared with controls. The comparison between the two PVD groups with different API values showed higher blood TG and VLDL-C values for the patients with lower API values (p < 0.05), indicating a relationship between hypertriglyceridemia and greater arterial damage. Key Words: Peripheral arterial occlusive disease-Triglyceride-Lipoprotein a.