Ankle brachial index and pneumoplethysmographic pulse-volume recordings for detection of peripheral arterial disease.

BACKGROUND: The measurement of the ankle-brachial index (ABI) is a straightforward method for the detection of atherosclerosis in the lower limbs. Pneumoplethysmographic pulse-volume recordings (PVR) investigations are supposed to be less valid. Thus we compared the sensitivity of ABI and PVR in detection of PAD and its improvement by combining both methods. PATIENTS AND METHODS: 122 consecutive patients admitted for PAD treatment were included. All patients (81 females; mean age 70 ± 15 years) had angiographic imaging of their peripheral arteries, a standardized personal interview and a determination of the ABI based on the highest (ABI high) and lowest (ABI low) ankle pressure. PVR parameters were oscillometric index (OI) and time to normalisation (TN) after exercise. RESULTS: There was a small variation of ABI with different segmental manifestations of PAD. The OI did not vary with different segmental manifestations. TN was longest in iliac artery manifestation and got shorter with more distal manifestation. Correlation of TN and ABI high and ABI low was low. Sensitivity of ABI high in all legs was 78 %, but only 40 % in isolated crural manifestation. ABI low has higher sensitivities with 87 % in all legs, but a much lower specificity. Combining ABI and TN increases both sensitivity and specificity. The best sensitivity and specificity was seen using ABI low + TN in combination in all kinds of manifestations with 94 % and 96 %, respectively. CONCLUSIONS: Combined assessment of ABI low and TN in post-exercise PVR seems to be a highly sensitive but also specific method to look for PAD compared to ABI high alone.

The variable number of tandem repeat polymorphism in the P-selectin glycoprotein ligand-1 gene is not associated with coronary heart disease.

Genes involved in inflammatory processes are candidates for predisposition to prothrombotic syndromes. The variable number of tandem repeat (VNTR) polymorphism in the P-selectin glycoprotein ligand (PSGL)-1 gene has been associated with ischemic cerebrovascular disease but not with coronary heart disease (CHD). We assessed the effect of the VNTR polymorphism on CHD in two independent case/control studies. In the first study 281 CHD patients and 397 healthy blood donors were genotyped for the VNTR alleles in PSGL-1. The prevalence of homozygous carriers of the PSGL-1 VNTR allele with 15 repeat units was significantly higher in the CHD patients (5.3% vs. 1.5%) than in controls, suggesting an effect of this marker in CHD. To validate the findings genotyping was performed in a second study including 2,578 CHD patients, 731 patients without CHD, and 1084 healthy blood donors. The larger case control study had a power of 99.9% to detect the initially observed difference but failed to confirm the putative role of PSGL-1 VNTR polymorphism in CHD. Frequencies of the PSGL-1 VNTR 15 repeats for homozygous carriers were 2.2% in healthy blood donors, 2.3% in patients without CHD and 2.7%, in CHD cases, respectively. These results demonstrate that the PSGL-1 VNTR polymorphism is not a genetic risk factor for CHD. Adequately powered studies are prerequisites to obtain reliable results about genotype-phenotype relationships of new candidate genes in complex diseases.

Predictive value of inflammatory and hemostatic parameters, atherosclerotic risk factors, and chest x-ray for aortic arch atheromatosis.

BACKGROUND AND PURPOSE: Aortic arch atheromatosis (AAA) is a common cause of cerebral embolism. Transesophageal echocardiography (TEE) shows not only the extension of atherosclerotic plaques but also the mobility of superimposed thrombi. In most cases AAA is only detected after the embolic event. This study was therefore designed to identify predictive factors for AAA. METHODS: One hundred seven consecutive patients referred for routine TEE were included in the study. Patients on warfarin therapy, with a history of recent surgery, or with any signs of infectious, immunological, or malignant diseases were excluded. RESULTS: Diabetes mellitus carried the highest risk for AAA (odds ratio, 3.0), followed by hyperlipidemia (2.5) and arterial hypertension (2.3). Age >70 years was accompanied with a 1.8-fold increased risk. Patients with aortic calcifications on standard chest x-ray had a 4.6-fold higher prevalence. Severe AAA was associated with higher levels of C-reactive protein (14.6+/-14.1 versus 4.9+/-7.2 mg/L), fibrinogen (4.20+/-1.22 versus 3.45+/-1.29 mg/L), plasmin/antiplasmin complexes (728+/-297 versus 453+/-243 microg/L), and D-dimers (980+/-652 versus 444+/-349 microg/L). CONCLUSIONS: AAA is accompanied by elevation of inflammatory and hemostatic parameters. Patients with classic cardiovascular risk factors and aortic calcifications on chest x-ray have a higher prevalence. Further prospective studies are now warranted to establish a risk score to identify patients in whom TEE screening should be undertaken.

Time-dependent changes of hs-CRP serum concentration in patients with non-ST elevation acute coronary syndrome.

BACKGROUND: Atherosclerosis is typically associated with a low-grade vascular inflammation that can be measured with the highly sensitive C-reactive protein (hs-CRP) assay. Actually, acute coronary syndromes are thought to result from plaque rupture which is induced by the inflammatory process in the atherosclerotic tissue. Therefore, it is interesting to discuss the value of follow-up measurements of hs-CRP in patients with coronary artery disease (CAD). PATIENTS AND METHODS: The hs-CRP concentration of 133 patients consecutively admitted with an acute coronary syndrome (ACS) was measured on admission and after 6 months. The final assessment after 3 years was structured by questionnaire. RESULTS: 17 cardiac events occurred within 6 months, 30 during the following 3 years. The hs-CRP levels (median +/- SEM) decreased significantly (p < 0.001) from baseline (3.9 +/- 1.3 mg/l) to follow-up (2.9 +/- 0.9 mg/l). Subdivision according to cardiac events during the first observation period confirmed this decrease in patients without events (baseline: 3.9 +/- 1.5 mg/l, follow-up: 2.9 +/- 0.9 mg/l; p < 0.001), whereas patients with events showed a persistent elevation (baseline: 3.8 +/- 0.9 mg/l, follow-up: 4.1 +/- 1.0 mg/l; p = 0.426). Patients who developed a further event during the 6-month period showed hs-CRP levels at follow-up that were > 60% of the initial level. Interestingly, 80% of the events within the following 3 years occurred in patients with an hs-CRP level above this discriminator. With a follow-up hs-CRP value above this discriminator the relative risk of suffering an event was 3.4 (95% confidence interval 1.27-8.9; p < 0.05). CONCLUSION: Patients with a non-ST elevation ACS who showed no event within 6 months are characterized by a decrease in hs-CRP levels from baseline to follow-up. Most events in the observation period of 3 years occurred in patients with follow-up hs-CRP levels > 60% of the initial level. Therefore, it was hypothesized that a repeated measurement of hs-CRP levels in CAD patients could help to discriminate those at high risk of further events.

Polymorphisms in the P-selectin (CD62P) and P-selectin glycoprotein ligand-1 (PSGL-1) genes and coronary heart disease.

P-selectin and its ligand, PSGL-1, are cell adhesion molecules that facilitate interaction of platelets, leukocytes and endothelial cells. Polymorphisms of these genes have been reported to be associated with coronary heart disease (CHD). In the present study, we characterized the entire coding regions of P-selectin and PSGL-1 genes in CHD patients and healthy controls. The 17 exons of the P-selectin gene and exon 2 of the PSGL-1 gene were screened for single nucleotide polymorphisms (SNPs) by exon re-sequencing in 88 CHD patients and 96 controls. For rapid genotyping of the SNPs we developed PCR techniques with sequence-specific primers (PCR-SSP). By using PCR-SSPs we genotyped 261 CHD patients and 214 controls for 5 SNPs in P-selectin and 2 SNPs in PSGL-1. In addition to the already described SNPs in P-selectin (S290N, N562D, V599L and T715P), we identified a novel SNP in exon 5 (V168M). The P-selectin 715P allele was more frequent among CHD patients with hypercholesterolemia compared to patients with normal cholesterol levels. A SNP (M621) in the PSGL-1 gene was found close to the P-selectin binding site and the 621 allele revealed a higher prevalence in the control group indicating a protective effect of the mutation. The molecular characterization of P-selectin and PSGL-1 in a case-control study including CHD patients and healthy controls revealed evidence for association of the genes with development of the disease. However, the functional role of the gene variants should be elucidated by further experimental data.