Pietro Fratino

Relationship Between Erectile Dysfunction and Silent Myocardial Ischemia in Apparently Uncomplicated Type 2 Diabetic Patients

Background—Erectile dysfunction (ED) is associated with coronary artery disease (CAD). In diabetic patients, CAD is often silent. Among diabetic patients with silent CAD, the prevalence of ED has never been evaluated. We investigated whether ED is associated with asymptomatic CAD in type 2 diabetic patients. Methods and Results—We evaluated the prevalence of ED in 133 uncomplicated diabetic men with angiographically verified silent CAD and in 127 diabetic men without myocardial ischemia at exercise ECG, 48-hour ambulatory ECG, and stress echocardiography. The groups were comparable for age and diabetes duration. Patients were screened for ED using the validated International Index of Erectile Function (IIEF-5) questionnaire. The prevalence of ED was significantly higher in patients with than in those without silent CAD (33.8% versus 4.7%; P =0.000). Multiple logistic regression analysis showed that ED, apolipoprotein(a) polymorphism, smoking, microalbuminuria, HDL, and LDL were significantly associated with silent CAD; among these risk factors, ED appeared to be the most efficient predictor of silent CAD (OR, 14.8; 95% CI, 3.8 to 56.9). Conclusions—Our study first shows a strong and independent association between ED and silent CAD in apparently uncomplicated type 2 diabetic patients. If our findings are confirmed, ED may become a potential marker to identify diabetic patients to screen for silent CAD. Moreover, the high prevalence of ED among diabetics with silent CAD suggests the need to perform an exercise ECG before starting a treatment for ED, especially in patients with additional cardiovascular risk factors.

Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease.

BackgroundDiabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease. Methods and ResultsTo assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44±2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03–0.15 Hz) and high-frequency (HF, 0.18–0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95±0.12 In-msece versus 6.73±0.11, p<0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11±0.18 In-msece versus 6.52±0.14, p<0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects. ConclusionsDiabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present.

Relationship between phasic changes in human skin blood flow and autonomic tone

Heart rate beat-to-beat oscillations synchronous with respiration and blood pressure waves, have been found to be a marker of sympathovagal interaction in man and animals. Oscillations of heart rate, respiration, and cutaneous blood flow were simultaneously recorded to assess the relationship between autonomic nervous control and cutaneous circulation in a group of 21 healthy subjects and in a group of 6 healthy patients after brachial plexus anesthesia and consequent sympathetic blockade. In the first group, changes in posture were employed to modify autonomic tone. Relative changes in cutaneous blood flow were recorded by laser-Doppler flowmetry. Spectral analysis techniques (cross-correlation) were used to quantify the relationship between oscillations common to the recorded signals. A standing maneuver induced a significant decrease of the cross-correlation between respiratory and heart rate fluctuations (from 4.93 +/- 0.16 to 4.44 +/- 0.16 a.u.; P less than 0.001), and a significant increase of the cross-correlation between heart rate and skin blood flow fluctuations (from 0.64 +/- 0.31 to 1.33 +/- 0.21 a.u.; P less than 0.001), but did not modify the cross-correlation between respiratory and skin blood flow fluctuations (from 2.87 +/- 0.15 to 3.04 +/- 0.14 a.u.; NS). After the standing maneuver the maximum correlation between heart rate and skin blood flow was always due to oscillations in the range of 0.1 Hz (or 10-sec period), similar to the oscillations described in large arteries. Sympathetic blockade reduced significantly the cross-correlation between heart rate and skin blood flow (P less than 0.001). These results suggest that the cross-correlation between skin blood flow and heart rate at 10-sec period fluctuations can be used as an index of the influence of the autonomic tone on skin blood circulation.

Association between Apolipoprotein(a) phenotypes and coronary heart disease at a young age

OBJECTIVES The purpose of this study was to investigate lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] phenotypes in relation to age of onset of coronary heart disease (CHD). BACKGROUND Although Lp(a) levels have been extensively analyzed in relation to age of CHD, apo(a) phenotypes have not. METHODS Three hundred and thirty-five consecutive CHD patients were enrolled and grouped according to their age of CHD onset (<45 years; 45 to 54 years; > or = 55 years). RESULTS In each patient group Lp(a) levels were higher than in an age-matched control group, but among the patient groups no differences in Lp(a) levels were observed. Apolipoprotein(a) phenotype distributions showed significant differences between patients and age-matched control subjects. Among the patient groups the difference in percentage of subjects with two apo(a) isoforms of low molecular weight (MW) was highly significant (p < 0.001). Multivariate analysis showed that apo(a) phenotypes were the best predictors of early CHD (p < 0.000001). The age-specific odds ratios (ORs) of the presence of at least one apo(a) isoform of low MW for CHD declined with age; in particular apo(a) phenotypes had their highest predictive value in younger persons (OR: 14.62). The OR for the presence of two isoforms of low MW/presence of only isoforms of high MW was 40.88 in the younger age group, 27.17 in age group of 45 to 54 years and 15.83 in the older age group. CONCLUSIONS The present article reports the first evidence of a strong independent association of apo(a) phenotypes with the age of onset of CHD. Thus, if our data are confirmed by larger studies, apo(a) phenotypes might be used together with Lp(a) levels as powerful genetic markers in assessing the actual risk of developing CHD at a young age.

Weight loss after Swedish Adjustable Gastric Banding: relationships to insulin resistance and metabolic syndrome.

Background:The metabolic syndrome is a cluster of cardiovascular risk factors (central obesity, hypertension,dyslipidemia, disturbance in glucose metabolism) associated with insulin-resistance. The cluster of risk factors defining the metabolic syndrome increases cardiovascular risk more than each single component. The aim of the present longitudinal study was to evaluate the relationship between weight loss and changes in insulin-resistance and in the prevalence of the metabolic syndrome 1-year after SAGB implantation. Methods: 51 premenopausal severely obese women (mean age 35.2±8.8 years, BMI 43.3±6.9) were enrolled. As a control group, 51 premenopausal nonobese women (BMI<30) were enrolled. All obese subjects underwent successful implantation of the SAGB via videolaparoscopy. In all subjects insulinresistance was estimated by HOMA index and metabolic syndrome was defined according to the criteria of the European Group for the Study of Insulin Resistance. Results: HOMA (4.2±2.0 vs 1.9±0.8, P<0.001) and the prevalence of the metabolic syndrome (58.8% vs 7.8%, P<0.001) were significantly higher in obese than non-obese women. 1 year after SAGB, BMI significantly decreased from 43.3±6.9 to 34.5±7.4 (P<0.001). HOMA index showed a significant dramatic breakdown (4.2±2.0 vs 2.4±1.0, P<0.001). The prevalence of the metabolic syndrome declined significantly (58.8% vs 21.6%, P<0.001). Conclusion: Our study shows that in severely obese women, insulin-resistance and the prevalence of the metabolic syndrome significantly decrease 1 year after SAGB. Our findings indicate that SAGB could be a useful tool to reduce the global cardiovascular risk in severely obese people and to improve their long-term prognosis.

Silent coronary artery disease in type 2 diabetes mellitus: the role of Lipoprotein(a), homocysteine and apo(a) polymorphism

BackgroundThere is little data on the relationship between novel cardiovascular risk factors and silent coronary artery disease (CAD) in diabetic patients. We investigated whether Lipoprotein(a), homocysteine and apolipoprotein(a) polymorphism are associated with angiographically assessed asymptomatic coronary artery disease (CAD) in diabetic patients.Methods1,971 type 2 diabetic patients without clinical signs of cardiovascular diseases and with a negative history of CAD were consecutively evaluated. Among them, 179 patients showed electrocardiographic abnormalities suggestive of ischemia or previous asymptomatic myocardial infarction. These 179 patients were subjected to a non-invasive test for CAD (ECG stress testing and/or scintigraphy). Among patients with a highly positive stress testing (n = 19) or a positive scintigraphy (n = 74), 75 showed an angiographically documented CAD (CAD group). Seventy-five patients without CAD (NO CAD group) were matched by age, sex and duration of diabetes to CAD patients. In NO CAD patients an exercise ECG test, a 48-hour ambulatory ECG and a stress echocardiogram were negative for CAD.ResultsLipoprotein(a) levels (22.0 ± 18.9 versus 16.0 ± 19.4 mg/dl; p < 0.05), homocysteine levels (13.6 ± 6.6 versus 11.4 ± 4.9 mmol/l; p < 0.05) and the percentage of subjects with at least one small apolipoprotein(a) isoform (70.7% versus 29.3%; p < 0.0001) were higher in CAD than NO CAD group. Logistic regression analysis showed that apolipoprotein(a) polymorphism (OR:8.65; 95%CI:3.05–24.55), microalbuminuria (OR:6.16; 95%CI:2.21–17.18), smoking (OR:2.53; 95%CI:1.05–6.08), HDL (OR:3.16; 95%CI:1.28–7.81), homocysteine (OR:2.25; 95%CI:1.14–4.43) and Lipoprotein(a) (OR:2.62; 95%CI:1.01–6.79) were independent predictors of asymptomatic CAD.ConclusionsThe present investigation shows an independent association of Lipoprotein(a), homocysteine and apo(a) polymorphism with silent CAD. Other studies are needed to establish whether these parameters are suitable for CAD screening in diabetic patients.

Relationship between fluctuations in heart rate and asymptomatic nocturnal ischaemia

In order to quantify autonomic changes related to asymptomatic nocturnal myocardial ischaemia, we analyzed heart rate fluctuations recorded during Holter monitoring in 9 subjects with coronary heart disease (21 episodes) and in 11 age-matched controls. R-R interval spectral analysis was computed in sequences of 256 heart beats, taken during the ischaemic episode, 4, 8 and 60 minutes before, and 4 and 60 minutes after. Mean heart rate, R-R interval variability (assessed by R-R interval standard deviation), low and high (respiration-linked) frequency components of R-R interval spectrum were evaluated. Mean heart rate and R-R interval variability increased only during ischaemia (from 62.9 to 73.3 beats/minute, P less than 0.02, and from 39 to 88 msec, P less than 0.01, respectively). While high-frequency components of heart rate variability remained unchanged, low-frequency peak increased during ischaemia (from 9.4 to 43.3 sec2 X 10(-3)/Hz, P less than 0.01) and also 8 minutes (P less than 0.05) and 4 minutes before (P less than 0.05). Despite a moderate increase of heart rate occurring only during ischaemia, the early rearrangement of heart rate fluctuations suggests the occurrence of changes of autonomic tone before the electrocardiographic onset of ischaemia. Due to its limited amount, this phenomenon appears to be a consequence, most likely unspecific, of factors responsible for the genesis of myocardial ischaemia.

Mining Healthcare Data with Temporal Association Rules: Improvements and Assessment for a Practical Use

The Regional Healthcare Agency (ASL) of Pavia has been maintaining a central data repository which stores healthcare data about the population of Pavia area. The analysis of such data can be fruitful for the assessment of healthcare activities. Given the crucial role of time in such databases, we developed a general methodology for the mining of Temporal Association Rules on sequences of hybrid events. In this paper we show how the method can be extended to suitably manage the integration of both clinical and administrative data. Moreover, we address the problem of developing an automated strategy for the filtering of output rules, exploiting the taxonomy underlying the drug coding system and considering the relationships between clinical variables and drug effects. The results show that the method could find a practical use for the evaluation of the pertinence of the care delivery flow for specific pathologies.

Mining Health Care Administrative Data with Temporal Association Rules on Hybrid Events

OBJECTIVE The analysis of administrative health care data can be helpful to conveniently assess health care activities. In this context temporal data mining techniques can be suitably exploited to get a deeper insight into the processes underlying health care delivery. In this paper we present an algorithm for the extraction of temporal association rules (TARs) on sequences of hybrid events and its application on health care administrative databases. METHODS We propose a method that extends TAR mining by managing hybrid events, namely events characterized by a heterogeneous temporal nature. Hybrid events include both point-like events (e.g. ambulatory visits) and interval-like events (e.g. drug consumption). The definition of user-defined rule templates can be optionally used to constrain the search only to the extraction of a subset of interesting rules. A TAR post-pruning strategy, based on a case-control approach, is also presented. RESULTS We analyzed the administrative database of diabetic patients in charge to the regional health care agency (ASL) of Pavia. TAR mining allowed to find patterns specifically related to the diabetic population in comparison with a control group, as well as to check the compliance of the actual clinical careflow with the ASL recommendations. CONCLUSION The experimental results highlighted the main potentials of the algorithm, such as the opportunity to detect interesting temporal relationships between diagnostic or therapeutic patterns, or to check the adherence of past temporal behaviors to specific expected paths (e.g. guidelines) or to discover new knowledge that could be implicitly hidden in the data.

Lipoprotein(a) levels and apolipoprotein(a) polymorphism in type 1 diabetes mellitus: relationships to microvascular and neurological complications

Abstract To investigate plasma concentrations of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] polymorphism in relation to the presence of microvascular and neurological complications in type 1 diabetes mellitus, 118 young diabetic patients and 127 age-matched controls were recruited. Lp(a) levels were higher in patients than in controls, but the apo(a) isoforms distribution did not differ between the two groups [higher prevalence of isoforms of high relative molecular mass (RMM) in both groups]. Microalbuminuric patients had Lp(a) levels significantly greater than normoalbuminuric patients, and normoalbuminuric patients showed higher Lp(a) levels than controls. Patients with retinopathy or neuropathy showed similar Lp(a) levels to those without retinopathy or neuropathy. No differences in apo(a) isoforms frequencies were observed between subgroups with and without complications (higher prevalence of isoforms of high RMM in every subgroup). However, among patients with retinopathy, those with proliferative retinopathy had higher Lp(a) levels and a different apo(a) isoforms distribution (higher prevalence of isoforms of low RMM) than those with non-proliferative and background retinopathy (higher prevalence of isoforms of high RMM). Our data suggest that young type 1 diabetic patients without microalbuminuria have Lp(a) levels higher than healthy subjects of the same age. Lp(a) levels are further increased in microalbuminuric patients. High Lp(a) levels and apo(a) isoforms of low RMM seem to be associated with the presence of proliferative retinopathy, but have no relation to neuropathy.