Hypolipidemic drugs in elderly subjects: Indications and limits.

AIMS: Cardiovascular disease is a major cause of death worldwide. Safety and efficacy of lipid lowering therapy have been clearly established for either primary and secondary prevention of cardiovascular events in adults. Nevertheless, the use of hypolipidemic drugs in elderly individuals, especially in the oldest ones, still raises some concerns. Aim of this paper is to review indications and limits of lipid lowering in advanced age, furnishing a practical medical attitude tempered by clinical and geriatric competences. DATA SYNTHESIS: While figures from randomized controlled trials and from observational studies seem to support the use of lipid lowering drugs for secondary prevention in the elderly, drawing inferences from primary prevention in old populations is far more challenging. Although these pharmacological agents seem to reduce the incidence of cardiovascular events, they do not prolong survival. In addition, there is some doubt about the cost-effectiveness of treatment because of a more delicate balance between benefit and potential adverse reactions. However, lipid-lowering drugs seem largely underutilized in older age, mainly due to safety concerns that must be reconsidered, at least in part, given the somewhat reassuring results deriving from specific cohort surveys. CONCLUSIONS: Data on the use and on the effects of lipid lowering drugs in elderly populations are incomplete, especially those concerning very old subjects without established cardiovascular disease. Comprehensive guidelines for the management of dyslipidemias in this rapidly-growing population is a urgent need, and treatment should be based, besides the aforementioned considerations, on patient preferences, cognitive function and life expectancy.

The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial.

OBJECTIVE: Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide. METHODS: Existing lipid-lowering therapy, including apheresis, was to remain stable from Week -6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide. RESULTS: Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (-48%) and not treated (-55%) with apheresis (p = 0.545). Changes in Lp(a) levels were modest and not different between groups (p = 0.436). CONCLUSION: The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis.

Flow-mediated dilation, carotid wall thickness and HDL function in subjects with hyperalphalipoproteinemia.

BACKGROUND AND AIMS: The relationships between very high plasma HDLc and subclinical atherosclerosis are still a matter of debate. METHODS AND RESULTS: Twenty subjects with primary hyperalphalipoproteinemia (HAL, with HDLc in the highest 10th percentile and absence of overt secondary causes of this condition), aged 30-65 years, were compared with 20 age and sex-matched controls. Lipid determination, lipoprotein particle distribution (Lipoprint(®)), Cholesterol Efflux Capacity (CEC), plasma adhesion molecule, analyses of CETP, SRB1 and LIPG genes and of different markers of subclinical vascular disease (ankle-brachial index, ABI; carotid intima-media thickness, cIMT; brachial-artery flow mediated dilation, FMD) were performed. Fasting HDLc levels were 40 mg/dl higher in HAL subjects while LDLc concentration was comparable to control group. CETP gene analysis in HAL subjects identified one novel rare Single Nucleotide Polymorphism (SNP, Asp131Asn), possibly damaging, while the common SNP p.Val422Ile was highly prevalent (50% vs. 27.4% in a control population). No rare mutations associated with HAL were found in SR-B1 and LIPG genes. Polyacrylamide gel electrophoresis in HAL subjects disclosed larger and more buoyant HDL particles than in controls, while LDL profile was much more similar. ABI, cIMT and arterial plaques did not differ in cases and controls and the two groups showed comparable FMD at brachial artery examination. Similarly, ABCA1 and ABCG1 HDL-mediated CEC, the most relevant for atheroprotection, did not discriminate between the groups and only ABCG1 pathway seemed somewhat related to arterial reactivity. CONCLUSIONS: HDL dimension, function and genetics seem scarcely related to subclinical atherosclerosis and vascular reactivity in middle-aged HAL subjects.

Role of antioxidants in atherosclerosis: epidemiological and clinical update.

Low density lipoprotein (LDL) oxidative modification in the vascular wall seems to be a key factor in atherosclerosis development. Oxidised LDLs might recruit monocytes and favour their transformation into foam cells through a receptor-mediated intake (scavenger pathway). Moreover oxidised LDLs show cytotoxic potential which is probably responsible for endothelial cell damage and macrophage degeneration in the atherosclerotic human plaque. Following the oxidation hypothesis of atherosclerosis the role of natural antioxidants, i.e. Vitamin C, Vitamin E and carotenoids, has been investigated in a large number of epidemiological, clinical and experimental studies. Animal studies indicate that dietary antioxidants may reduce atherosclerosis progression, and observational data in humans suggest that antioxidant vitamin ingestion is associated with reduced cardiovascular disease, but the results of randomised controlled trials are mainly disappointing. It has been suggested that natural antioxidants may be effective only in selected subgroups of patients with high levels of oxidative stress or depletion of natural antioxidant defence systems. The favourable effects shown by some studies relating antioxidant dietary intake and cardiovascular disease, may have been exerted by other chemicals present in foods. Flavonoids are the ideal candidates, since they are plentiful in foods containing antioxidant vitamins (i.e. fruits and vegetables) and are potent antioxidants. Tea and wine, rich in flavonoids, seem to have beneficial effects on multiple mechanisms involved in atherosclerosis. Future studies should probably select patients in a context of high-oxidative stress / low-antioxidant defence, to verify if antioxidants may really prove useful as therapeutic anti-atherosclerotic agents.

Testosterone replacement, cardiovascular system and risk factors in the aging male.

Investigations concerning the role of testosterone replacement on cardiovascular risk show conflicting results. Treatments with supraphysiological doses seem detrimental in animal models and men. On the other hand, cross-sectional, prospective and angiographic studies frequently find an inverse, favorable relationship between plasma testosterone and cardiovascular events. Testosterone replacement therapy in the hypogonadic elderly has a positive or at least neutral effect on several coronary disease risk factors. Testosterone appears to decrease LDL-cholesterol without adversely affecting HDL cholesterol, and improve insulin sensibility and the thrombotic/fibrinolytic balance; testosterone does not negatively influence the inflammatory response and arterial wall vasoreactivity. These findings provide a measure of reassurance concerning potential adverse heart effects of testosterone substitutional therapy in older men, even if more specific trials than reported are needed to overcome residual suspicions.

Endothelial function and postprandial lipemia.

It is widely recognised that post-prandial lipoproteins play a role in the development of atherosclerosis, but the mechanisms underlying this role are unclear. An attractive working hypothesis is that the pathogenetic link is endothelial dysfunction. The available data seem to corroborate this theory and recognise triggering by oxidative stress, but some of the evidence is still contradictory.

Risk of hospitalization for upper gastrointestinal tract bleeding.

OBJECTIVE: This study evaluates the hospitalization risk for upper gastrointestinal bleeding (UGIB) with reference to the clinical characteristics of patients and drugs taken before admission. METHODS: This study is based on the GIFA (Italian Group for the Pharmacosurveillance in the Elderly) database. Cases with an ICD-9 code of esophagus, stomach or duodenum bleeding, or acute esophago-gastroduodenal disease associated with anemia have been classified as UGIB. Sex, age, year of observation, drugs taken at home, comorbidity, smoking, alcohol, and use of gastroprotectants have been also taken into account. Statistical analysis has been conducted using multivariate logistic regression models. RESULTS: 32,388 patients have been enrolled, 940 of which presented UGIB. Age, comorbidity, use of smoke and alcohol, hospitalization duration, and mortality during hospitalization were significantly higher in UGIB than nonUGIB patients. Increased UGIB risk has been found in patients taking NSAIDs (both when aspirin was included or excluded), acetaminophen, constipating agents, iron, ethacrynic acid, propranolol. Reduced UGIB risk has been found in patients taking nitrates. CONCLUSIONS: UGIB risk appears to correlate with clinical characteristics of the patient: it increases with age, comorbidity, and smoke and alcohol consumption. Among drugs, NSAIDs are associated with the highest UGIB risk, while nitrates with a reduction of risk.

Reversible hyperthyroidism and cardiomyopathy caused by consumption of iodocasein.

We report the case of a 52-year-old woman with recent diagnosis of acute myocarditis and pericarditis, admitted for fever, tachycardia, and dyspnea upon exertion. Hematochemical parameters and instrumental examinations suggested iatrogenic hyperthyroidism and secondary dilated cardiomyopathy. Although gathering information about the medication used at home was initially difficult because of the patient's refusal to cooperate, she ended up by disclosing the regular assumption of an iodocasein drug. A complete and stable regression of the clinical picture was reached by suspending the iodine derivative and using cardiovascular drugs.

Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial.

BACKGROUND AND AIM: Postmenopausal modification of the lipid profile plays a major role in the risk of ischemic heart disease. Lifestyle counseling and estrogen replacement therapy have all been proposed as first-line measures, but there is no agreement on the best way to treat climacteric dyslipidemia. Soybean-based diet seems particularly attractive in this context, given its cholesterol lowering potential, its hypothetical anticancerous effects and possible modification of climacteric symptoms. METHODS AND RESULTS: We evaluated the effect of 60 g isolated soy protein (ISP) daily on the lipid profile of 104 postmenopausal women (53.3 +/- 3.3 years) in a double-blind, parallel, placebo-controlled (caseinate) trial, as part of a broader assessment of the effect of ISP on climacteric symptomatology. Serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I, apo B and lipoprotein (a) were determined before and after a 12-week diet modification. Seventy-seven women completed the trial. Both soy and placebo determined a significant reduction in total cholesterol (-0.42 +/- 0.79 and -0.40 +/- 0.57 mmol/L) and LDL-cholesterol (-0.35 +/- 0.72 and -0.31 +/- 0.54 mmol/L), but only soy had a significant lowering effect on apo B and the LDL-cholesterol/HDL-cholesterol ratio (-6% and -8% from baseline respectively); lipoprotein (a) plasma levels were not significantly changed by either treatment. Forty-four women were dyslipidemic at baseline; those with increased LDL concentrations showed a somewhat greater improvement in their lipoprotein profile (LDL-cholesterol and apo B reduction) with soy rather than placebo. No further information emerged when the subjects were divided into three apo E phenotypes. CONCLUSIONS: We conclude that diet supplementation with 60 g ISP is slightly better than caseinate in favorably modifying the lipoprotein metabolism of postmenopausal women; this effect is more evident in hypercholesterolemic subjects.

Post-prandial effects of gemfibrozil vs simvastatin in hypercholesterolemic subjects with borderline hypertriglyceridemia.

BACKGROUND AND AIM: Impaired triglyceride-rich lipoprotein metabolism is most probably related to an enhanced cardiovascular risk, and may be associated with a pro-coagulant state. A double-blind, randomized study was undertaken to evaluate two widely utilized hypolipidemic drugs in the post-prandial phase and their impact on lipid, coagulation and fibrinolytic parameters. METHODS AND RESULTS: Thirty middle-aged men selected according to their low density lipoprotein-cholesterol (LDL-C) > or = 160 and < or = 240 mg/dl and borderline hypertriglyceridemia (110-220 mg/dl) after at least one month of a lipid-lowering diet received gemfibrozil (600 mg bid) or simvastatin (20 mg qd) and the corresponding placebo. On enrollment and after 2 months of drug treatment, they were tested with a standard oral fat load (OFL) (35 g fat/m2 body surface). On both occasions plasma total-cholesterol, LDL-C, HDL-C, triglycerides, lipoprotein[a] (Lp[a]), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), antithrombin-III (AT-III), plasminogen and fibrinogen were determined just before the meal (t0) and at times 2 hours, 4 h, 6 h, 8 h after it (t2-t8). A two-factor (time and visit) multivariate analysis for repeated measurements was performed to evaluate the data. Total cholesterol, and LDL-C were significantly diminished 2 months after both gemfibrozil and simvastatin, the latter being more active. Plasma triglycerides showed a marked reduction with gemfibrozil at all times, while simvastatin regimen yielded only minor modifications. HDL-C was only slightly increased by simvastatin; Lp[a] plasma levels were almost unaffected. Small fibrinogen (t0, t2, t6, t8), PAI-1 (t6) and AT III (t0-t8) increases were observed after gemfibrozil, while simvastatin did not significantly modify these parameters. CONCLUSIONS: In the post-prandial phase, gemfibrozil and simvastatin induce different metabolic effects that beneficially influence the lipid pattern, whereas fibrinolytic and coagulative parameters display minor variations of undetermined significance.

Plasma lipoprotein composition, apolipoprotein(a) concentration and isoforms in beta-thalassemia.

Patients with homozygous beta-thalassemia show an abnormal lipoprotein profile. In asymptomatic heterozygotes the lipid pattern is less markedly affected but interestingly related to a diminished cardiovascular risk. The extent and significance of these findings are still a matter of debate and no data are available on lipoprotein(a) plasma levels. Seventy patients with homozygous beta-thalassemia (HT-P), 70 beta-thalassemia trait carriers (TT-C) and 70 sex and age-matched controls were investigated and their plasma lipoprotein profile and apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12 TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous beta-thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration than TT-C (-7, -11, -8, -8, -13 and +11%, respectively) or controls (-39, -50, -46, -32, -30 and + 35%, respectively). All lipoprotein subclasses were triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein-depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B plasma levels but only minor lipoprotein abnormalities with respect to the controls. BMT-P lipoprotein composition was intermediate between HT-P and normal subjects. Apo(a) plasma levels did not differ among the groups. A higher prevalence of 'small' apo(a) isoforms was present in HT-P. Within the same 'isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT-C or controls. Since liver cirrhosis is almost always present in HT-P, it is conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to diminished apolipoprotein glycation may be involved. In TT-C a partially improved cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and apo B), thus justifying the claim for a low prevalence of ischemic heart disease, but no Lp(a) plasma level modification could be detected.

[Low levels of HDL cholesterol in hypothyroid patients with cardiovascular diseases]. / Ridotti livelli di colesterolo HDL nelle pazienti ipotiroidee con malattie cardiovascolari.

BACKGROUND: Hypothyroidism is a frequent cause of hyperlipidemia, particularly in women, but its true prevalence, both in the general population and in dyslipidemic subjects, is unknown. It is uncertain if low thyroid function significantly influence HDL metabolism and if sub-clinical disease may cause metabolic abnormalities and increase cardiovascular risk. METHODS: Three-hundred and three consecutive female patients (mean age 59.2 +/- 0.5 yrs), observed in a metabolic ward because of dyslipidemia, were evaluated. RESULTS: Forty-three women (14.1% of the total) showed sub-clinical hypothyroidism, while in 12 cases (4.0%) overt hypothyroidism was diagnosed; 8 further women (2.6%) had been previously diagnosed to be hypothyroid and were under hormone replacement therapy. On the whole, hypothyroid patients showed higher mean triglyceride levels and lower HDL-cholesterol than dyslipidemic euthyroid women, but the difference did not reach statistical significance. Total cholesterol concentration did not change with impaired thyroid function. Hypothyroid patients reported a clinical history of cardiovascular disease, or had severe atherosclerosis demonstrated, more often than euthyroid subjects (25.0% vs 19.7%, p = n.s.). When only women with arterial disease were considered, HDL plasma levels were significantly lower in the hypothyroid than in the euthyroid group (44.3 +/- 3.1 vs 56.2 +/- 1.7 mg/dl, respectively; p < 0.01). Hypertriglyceridemia and obesity often coexisted. CONCLUSIONS: In conclusion, among dyslipidemic women, unrecognised hypothyroidism is highly prevalent (both sub-clinical and manifest). In hypothyroid subjects atherosclerosis seem to associate with particularly low HDL plasma levels. This might precede atherosclerosis development (reinforced by concomitant thyroid failure) and represent a marker of the polymetabolic syndrome.

[Short term changes in risk factors of cerebrovascular diseases. A failure of preventive measures?]. / Modificazioni nel breve termine dei fattori di rischio delle malattie cerebrovascolari. Un insuccesso degli interventi di prevenzione?

BACKGROUND AND PURPOSE: Stroke is the third main cause of death in western countries. To evaluate its ever-changing characteristics and the impact of recent public campaigns on cardiovascular risk factors (CRFs) in stroke morbidity and mortality, we carried out a retrospective investigation on subjects with cerebrovascular disease in different periods. METHODS: All clinical data of patients with acute cerebrovascular disease (TIA or stroke) admitted to a regional hospital (Padua, Italy) during two distinct years (1985 and 1992) were examined (381 in 1985 and 440 in 1992). In every case the characteristics of the episode, clinical course, concomitant CRFs and relevant biochemical and instrumental examinations were recorded. RESULTS: Altogether Transient Ischemic Attack (TIA) represented almost half the records; remaining cases could be classified as ischemic stroke (66% vs 55%), Intracerebral Haemorrhage (17% vs 26%) and subarachnoideal haemorrhage (17% vs 19%) (1985 vs 1992, respectively). The mean hospitalization period was longer in the most recent year, particularly in haemorrhagic patients (H-P, subarachnoid + intracerebral haemorrhage); the in-hospital case fatality rate was reduced in HP while it was significantly increased in those with Cerebral Ischemia (CI-P, TIA + ischemic stroke). The prevalence of blood hypertension, atrial fibrillation and dyslipidaemias rose significantly in 1992 compared to 1985. High plasma lipids were more frequently present in CI-P than in H-P; their 7-year increase was particularly related to combined forms, rather then isolated hypercholesterolemia or hypertriglyceridemia. CONCLUSIONS: These results do not agree with an hypothetical improvement in the prognosis of stroke in the period we considered. Besides the efforts aiming at reducing CRFs in the short term have not shown to be successful.

Dyslipidemia in peripheral vascular disease.

Peripheral atherosclerosis (carotid and aortofemoral vascular districts) shows some peculiar characteristics with respect to coronary atherosclerosis. In this paper we have reviewed the most recent studies on the relationships between atherosclerosis of the limbs and lipid metabolism. Several authors have described increased plasma levels of lipoprotein remnants, lipoprotein (a) and some lipid peroxidation parameters in extracoronary atherosclerosis, while HDL (and their subfractions) seem to be reduced. Some of these modifications may be related to the direct metabolic effects of smoking and diabetes, which frequently coexist. Recent intervention trials show a possible regression of established atherosclerotic plaques after hypolipidemic therapy. This further underscores the role of plasma lipoprotein pattern in determining peripheral vascular lesions.

Severe hypercholesterolaemia: unusual inheritance in an Italian pedigree.

A family presenting several cases of severe primary hypercholesterolaemia and/or premature sudden death was studied. This family is characterized by consanguinity, absence of vertical transmission, bimodal distribution of plasma cholesterol values, and reduction of reproductive fitness in affected individuals. The probands have clinical traits of homozygous familial hypercholesterolaemia, including hypercholesterolaemia, xanthomas and early coronary atherosclerosis, while the parents and grandparents are clinically normal. Eight relatives on the mother's side experienced premature sudden death, and in four cases hypercholesterolaemia was diagnosed. Haplotype segregation analysis of the inheritance of the LDL receptor and apo B genes in the probands' family excluded the involvement of these two genes in the pathogenesis of the disease. LDL receptor activity, as well as the ability of LDL to bind to the LDL receptor, and plasma vegetal sterols were within normal limits both in probands and in their relatives. The study of this pedigree suggests that hypercholesterolaemia is not produced by defects in the LDL receptor or LDL particles, and disease inheritance is consistent with an autosomal recessive trait.

Effect of age on the response of blood lipids, body composition, and aerobic power to physical conditioning and deconditioning.

The influence of age on the response of plasma lipids, body composition, and cardiovascular performance to physical training and detraining was studied in 12 older and 12 young adult male cyclists. The athletes were first examined at the peak of their seasonal preparation and then again 2 months after its suspension. Sedentary males matched for age, weight, and height comprised the respective control groups. During training, body fat mass (BFM) was significantly lower and maximum oxygen consumption (VO2max) higher in both groups of cyclists as compared with controls. No differences in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) B, apo A-II, and fibrinogen were found. During the same phase, triglycerides (TG) and the LDL-C to high-density lipoprotein cholesterol (HDL-C) ratio were significantly lower and apo A-I, HDL-C, HDL3-C, and the apo A-I/apo B ratio were significantly higher in the athletes than in their corresponding sedentary controls. After physical deconditioning, BFM increased and VO2max decreased significantly in both groups of athletes. TG, very-low-density lipoprotein cholesterol (VLDL-C), and fibrinogen increased in young athletes while the LDL-C/HDL-C ratio increased, and apo A-I, HDL-C, HDL2-C, and HDL3-C decreased significantly in both young and older athletes. Thus, an aerobic training program induced an antiatherogenic lipoprotein profile and beneficial modifications in body composition and aerobic power in both older and younger subjects; a 2-month interruption in the program changed these parameters unfavorably in both groups. Age does not seem to influence significantly the plasma lipid response to physical deconditioning.

[Comparative characteristics of electrocardiographic tracing in young subjects of various ethnic groups]. / Caratteristiche comparative del tracciato elettrocardiografico in soggetti giovani appartenenti a razze diverse.

In this study we evaluated the potential differences in normal electrocardiographic parameters between two groups of young patients belonging to different races (Caucasians and Blacks). For this purpose 100 electrocardiograms had been taken, coded and compared in 50 Italian males and 50 north-Africans who came to an Emergency Department because of minor condition. On the whole we could not find significant differences between the two groups, except for a small increase in P-wave duration in black people. We conclude that the same parameters used to evaluate normal electrocardiograms in white people, may be satisfactory applied also for black individuals. This fact is worthy of attention since more and more extracomunitarian patients are addressing the Italian Health Service.

[The incidence of acute myocardial infarct during the week. A chronobiological evaluation]. / Incidenza dell'infarto miocardico acuto durante la settimana. Una valutazione cronobiologica.

Several diseases, and particularly cardiovascular affections, show a periodic fluctuation in their occurrence. We investigated acute myocardial infarction (AMI) incidence in connection with the day of the week, looking for a link with psycho-social phenomena. Eight hundred and fifty-two patients with AMI were considered: they had been admitted to the emergency department of two main towns of northeastern Italy during a calendar year. Eight hundred and seventeen (533 men, 284 women) were eligible for the purpose of this study. The time of symptom onset was recorded, cardiovascular risk factors and occupational condition were evaluated. All data were analyzed through chi-square test of uniformity and Halberg single cosinor test. No statistically significant difference from the uniform distribution appeared in acute events occurrence both in patients as a whole and in single subgroups subdivided according to gender and age. However, the preferential distribution during the days of the week was somewhat different between men (highest incidence at the extreme of the week) and women (highest incidence about mid-week). Statistically significant differences in AMI occurrence in the week were evidenced when patients were analyzed after subdivision according to their occupational condition: working subjects, in comparison with not-working individuals, showed a higher AMI incidence at the beginning of the week with respect to subsequent days. It is therefore likely that the stress associated with the return to work (according to the weekly working pattern of western society) represents an additional important cause of AMI. The mechanisms for that are only speculative.

[Chronobiological approach to renal colic]. / Approccio cronobiologico alla colica renale.

The concentration of lithogenic and antilithogenic substances in urine shows circadian fluctuations. With this investigation we intended to verify the presence of a chronobiologic rhythm of colic pain in urinary tract calculosis. Four hundred and forty seven consecutive patients with a clinical symptomatology related to urinary tract colic pain were studied. They were subdivided according to sex and age (297 M, 150 F; > or = 65 ys 29, < 65 ys 428). Urinary and blood chemical analysis and instrumental examinations permitted to confirm the clinical diagnosis. To evaluate the circadian and circannual variability, acute events were grouped into one calendar year by the month and into a ideal day by the hour of occurrence respectively. Chronobiologic analysis was performed utilising Halberg single cosinor test. The results pointed out that the symptomatology related to urinary tract colic pain presents a circadian rhythmicity either in patients as a whole or in single subgroups (males, females, younger or older than 65 ys). Besides no seasonal variability was demonstrated, perhaps because of the mild climate present in the geographic area in which the study was carried on.