Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension

We have shown that the capacity for local release of tissue-type plasminogen activator (tPA) from the vascular endothelium is impaired in patients with primary hypertension. Because this response is an important protective mechanism against intravascular clotting, we investigated whether this system is also defective in patients with advanced chronic kidney disease and hypertension. Nine nondiabetic nonsmoking men with chronic kidney disease (glomerular filtration rate 11 to 28 mL/min x 1.73 m2; aged 33 to 75 years) were compared with age-matched healthy controls. Intraarterial infusions of desmopressin, methacholine, and sodium nitroprusside were given locally in the brachial artery. Forearm blood flow was measured by venous occlusion plethysmography and blood collected repeatedly during the desmopressin infusion for determination of stimulated net and total cumulated release of tPA. The maximal release rate of active tPA (P<0.05) and the capacity for acute tPA release were markedly impaired in the renal patients as compared with healthy subjects (ANOVA, P=0.013). Accordingly, the accumulated release of tPA was 1905 (SEM 366) and 3387 (718) ng/L tissue, respectively (P<0.05). However, there were no significant differences in vasodilator responses between the groups. Thus, patients with advanced chronic kidney disease and hypertension have a markedly impaired capacity for acute release of tissue plasminogen activator, despite preserved endothelium-dependent vasodilation. This defect may contribute to a defective local defense against arterial thrombosis.     

Clinical evaluation and stress test have limited value in the diagnosis of in-stent restenosis

Objectives. In-stent restenosis (ISR) is the main limitation of percutaneous coronary interventions (PCI), occurring in approximately 25% of cases. Although frequently asymptomatic, many PCI patients present with recurrent symptoms of chest pain at follow-up raising a clinical suspicion of ISR. The diagnosis of ISR can be challenging in these patients and difficult to rule out without repeat coronary angiography. Design. We prospectively investigated the diagnostic accuracy of clinical evaluation and exercise stress testing to detect ISR as compared to coronary angiography, in a consecutive, unselected cohort of PCI patients. Results. We studied 91 patients with a total of 143 stents. Clinical evaluation predicted ISR to be likely in 19% of cases and the exercise test was positive in 29%. The binary restenosis rate was 21%. Clinical evaluation had a positive predictive value of 29% and accuracy of 71%, while exercise stress testing had a positive predictive value of 19% and accuracy of 65%. Conclusion. In conclusion, we found the diagnostic accuracy of clinical evaluation to be low and not significantly improved by exercise stress testing when evaluating PCI patients for ISR.     

Comparison of interventional cardiology in two European countries: A nationwide internet based registry study

Background

The practice of interventional cardiology differs between countries and regions. In this study we report the results of the first nation-wide long-term comparison of interventional cardiology in two countries using a common web-based registry.

Methods

The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was used to prospectively and continuously collect background-, quality-, and outcome parameters for all coronary angiographies (CA) and percutaneous coronary interventions (PCI) performed in Iceland and Sweden during one year.

Results

The rate of CA per million inhabitants was higher in Iceland than in Sweden. A higher proportion of patients had CA for stable angina in Iceland than in Sweden, while the opposite was true for ST elevation myocardial infarction. Left main stem stenosis was more commonly found in Iceland than in Sweden. The PCI rate was similar in the two countries as was the general success rate of PCI, achievement of complete revascularisation and the overall stent use. Drug eluting stents were more commonly used in Iceland (23% vs. 19%). The use of fractional flow reserve (0.2% vs. 10%) and the radial approach (0.6% vs. 33%) was more frequent in Sweden than in Iceland. Serious complications and death were very rare in both countries.

Conclusion

By prospectively comparing interventional cardiology in two countries, using a common web based registry online, we have discovered important differences in technique and indications. A discovery such as this can lead to a change in clinical practice and inspire prospective multinational randomised registry trials in unselected, real world populations.     

Declining coronary heart disease mortality in Iceland: contribution by incidence,recurrence and case fatality rate

OBJECTIVE: To analyse to what extent the recent decline in coronary heart disease mortality in Iceland is due to changes in incidence, recurrence and case fatality rates. DESIGN: A countrywide registration of myocardial infarction (MI) in people aged 25-74 was performed in Iceland during 1981-1999 according to the MONICA protocol. Possible cases were found by review of all hospital discharge records, autopsy records and death certificates. RESULTS: MI death rate declined by 63% in males and 51% in females, most in the youngest age groups in men (86%) and least in the oldest (49%). In women there was not a significant difference in age groups. Overall the age-adjusted reduction in MI death rate was 55.4% in both sexes combined; of this 23.1% was due to incidence reduction, 22.8% to recurrence reduction and 11.6% to case fatality reduction. In the youngest age groups the decline in incidence contributed most to the decline in MI death rate (62% in men and 71% in women), but thereafter the decline in case fatality in men. In the older age groups decline in recurrence rate has greater weight. CONCLUSION: The recent decline in MI mortality under the age of 75 years in Iceland is due to reduction in incidence and recurrence rate by about 40% each and to reduction in case fatality by 20%.     

Size at birth and coronary artery disease in a population with high birth weight

BACKGROUND: Epidemiologic studies suggest a link between fetal and childhood growth and later coronary artery disease (CAD). The influence of adult body size on the relation between birth size and CAD has not been thoroughly studied. OBJECTIVE: We investigated the association between birth and adult sizes and CAD within a population with higher birth weight and a lower incidence of and mortality rate from CAD than those seen in other Scandinavian populations. DESIGN: Fatal or nonfatal CAD was ascertained in 2399 men and 2376 women born in the Greater Reykjavik area between 1914 and 1935. Birth size was obtained from the National Archives. Anthropometric measurements in adults were obtained from the randomized prospective Reykjavik Study. RESULTS: CAD was inversely related to birth length (P for trend = 0.029) in men but was not significantly related to birth weight or ponderal index (kg/m(3)). In men who were born short (< or = 50.5 cm) and who became tall adults (either 175-180.5 or > 180.5 cm), the odds ratios (95% CI) for CAD were 1.9 (1.1, 3.1) and 2.2 (1.2, 4.0), respectively, when compared with men in the reference group (those born 52.5-54.0 cm long). A U-shaped relation between birth size and CAD was found for women. CONCLUSIONS: Size at birth has an effect on CAD, but the effect is modified by adult body size. This confirms that environmental factors operate in both the prenatal and postnatal periods with regard to the development of CAD. The large birth size seen among Icelanders may explain the lower incidence and mortality rate of CAD in Iceland than are seen in other white populations.     

Familial risk of lung carcinoma in the Icelandic population

Context  The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established; however, an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma. Objective  To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icelandic population. Design, Setting, and Participants  Risk ratios (RRs) of lung carcinoma for first-, second-, and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2756 patients diagnosed with lung carcinoma within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The RR for smoking was similarly estimated using a random population-based cohort of 10 541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR. Main Outcome Measures  Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers. Results  A familial factor for lung carcinoma was shown to extend beyond the nuclear family, as evidenced by significantly increased RR for first-degree relatives (for parents: RR, 2.69; 95% confidence interval [CI], 2.20-3.23; for siblings: RR, 2.02; 95% CI, 1.77-2.23; and for children: RR, 1.96; 95% CI, 1.53-2.39), second-degree relatives (for uncles/aunts: RR, 1.34; 95% CI, 1.15-1.49; and for nephews/nieces: RR, 1.28; 95% CI, 1.10-1.43), and third-degree relatives (for cousins: RR, 1.14; 95% CI, 1.05-1.22) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age at onset 60 years) (for parents: RR, 3.48; 95% CI, 1.83-8.21; for siblings: RR, 3.30; 95% CI, 2.19-4.58; and for children: RR, 2.84; 95% CI, 1.34-7.21). The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships, except cousins and spouses, with a single-sided test of the RRs for lung carcinoma vs RRs for smoking. Conclusions  These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.      

Response to drugs and diet in a compound heterozygote for familial hypercholesterolaemia

A boy with a total plasma cholesterol concentration of 20.9 mmol/l which fell significantly with a low fat diet, cholestyramine and simvastatin, was shown to have two different mutations in the low density lipoprotein receptor gene, demonstrating that some patients with homozygous familial hypercholesterolaemia show a good lipid lowering response to treatment.