Predicting sudden cardiac death using common genetic risk variants for coronary artery disease.

AIMS: Genome-wide association studies (GWAS) have identified many variants associating with an increased risk of coronary artery disease (CAD). We studied the possible association between these variants and the risk of sudden cardiac death (SCD). METHODS AND RESULTS: A weighted genetic risk score (GRSCAD) was formed from variants most strongly associating with CAD identified by the CARDIoGRAMplusC4D Consortium explaining 10.6% of the heritability of CAD [153 single-nucleotide polymorphisms with r(2) < 0.2]. The association between GRSCAD and the occurrence of SCD was studied in three independent autopsy series of consecutive cases combining altogether 1035 autopsies with 306 SCDs due to CAD (SCDCAD). The results were replicated in a prospective follow-up study of 2321 patients (mean follow-up time of 6.2 years with 48 incident SCDs of which 39 due to CAD) undergoing clinical exercise test at baseline. In a meta-analysis of the autopsy series, GRSCAD associated significantly with the risk of SCDCAD with age, body mass index, and sex adjusted odds ratio (OR) of 1.042 (1.023-1.061, P = 9.1 × 10(-6)) for one allele increase in GRSCAD. The same association was seen in both sexes. GRSCAD predicted significantly the risk of SCDCAD also in a prospective study setting (Cox regression analysis adjusted with all relevant clinical data): hazard ratio 1.049 (1.010-1.090, P = 0.014). In meta-analysis of all cohorts (adjusting further for other genetic markers related to traditional risk factors and QT-interval), the association was highly significant [OR 1.045 (1.028-1.063), P = 1.7 × 10(-7)]. CONCLUSION: Genetic risk estimate for CAD may also be used to predict SCD.

Sex differences in coronary atherosclerosis during the pre- and postmenopausal period: The Tampere Sudden Death Study.

BACKGROUND AND AIMS: Women are believed to be protected from coronary heart disease (CHD) by the effects of estrogen but detailed studies on the vessel wall level are missing. We aimed to measure sex differences in atherosclerosis during the premenopausal and postmenopausal periods directly at the coronary arteries. METHODS: We analyzed statistics for sex differences in CHD mortality in Finland in 2020. Coronary atherosclerosis was measured using computer-assisted morphometry in 10-year age groups of 185 white Caucasian women and 515 men from the Tampere Sudden Death Study. RESULTS: CHD mortality was rare in both women and men before 50 years of age. After 50 years of age, male mortality increased rapidly, with women reaching equal levels in the oldest age groups. In the autopsy series, there were no differences in fatty streak, fibrotic or calcified plaque areas, nor in the plaque area or stenosis percentage in coronary arteries between premenopausal women and men in the same age group. The plaque area remained 25 % smaller in both coronaries in postmenopausal women aged 51-70 years compared to men. In the oldest postmenopausal group (≥70 years), plaque area reached the level of men. In the postmenopausal period, coronary stenosis in the left anterior descending (LAD) artery remained lower among women. CONCLUSION: We did not detect any major sex-difference in coronary atherosclerosis in the premenopausal period when women are considered to be protected from CHD. However, in line with CHD mortality statistics, postmenopausal women showed a slower speed of coronary atherosclerosis development compared to men.

Human brain tissue microarrays as a platform to investigate diseases of the nervous system.

We constructed tissue microarray (TMA) blocks containing post-mortem human brain tissue from subjects with clinically and neuropathologically verified Alzheimer's disease (AD), corticobasal degeneration (CBD), progressive supranuclear palsy, Lewy body disease, multisystem atrophy (MSA) as well as an age matched control. Fifteen donor blocks were merged into two TMA blocks containing 72, 2-mm punch core samples with representative brain regions generally affected in degenerative disorders. Hyperphosphorylated-gamma, alpha-synuclein and beta-amyloid-related pathologies were estimated. The diseases were easily recognized by evaluating the two TMA sections and the results assessing TMA sections were comparable with the assessment of the whole brain sections. The assessment of TMA sections revealed concomitant multifocal alpha-synuclein pathology in AD, mild tau-involvement in the case of MSA and a slight AD-type pathology in the case of CBD. These findings emphasize the importance of searching for a variety of pathologies in "the whole brain" rather than restricting the examination to a few vulnerable regions. Furthermore, the TMA methodology clearly reduced the number of sections needed for evaluating the whole brain, it increased the amount of research material generated and furthermore no detailed neuroanatomical knowledge was required for assessment of data.

Oral bacterial DNA findings in pericardial fluid.

BACKGROUND: We recently reported that large amounts of oral bacterial DNA can be found in thrombus aspirates of myocardial infarction patients. Some case reports describe bacterial findings in pericardial fluid, mostly done with conventional culturing and a few with PCR; in purulent pericarditis, nevertheless, bacterial PCR has not been used as a diagnostic method before. OBJECTIVE: To find out whether bacterial DNA can be measured in the pericardial fluid and if it correlates with pathologic-anatomic findings linked to cardiovascular diseases. METHODS: Twenty-two pericardial aspirates were collected aseptically prior to forensic autopsy at Tampere University Hospital during 2009-2010. Of the autopsies, 10 (45.5%) were free of coronary artery disease (CAD), 7 (31.8%) had mild and 5 (22.7%) had severe CAD. Bacterial DNA amounts were determined using real-time quantitative PCR with specific primers and probes for all bacterial strains associated with endodontic disease (Streptococcus mitis group, Streptococcus anginosus group, Staphylococcus aureus/Staphylococcus epidermidis, Prevotella intermedia, Parvimonas micra) and periodontal disease (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Fusobacterium nucleatus, and Dialister pneumosintes). RESULTS: Of 22 cases, 14 (63.6%) were positive for endodontic and 8 (36.4%) for periodontal-disease-associated bacteria. Only one case was positive for bacterial culturing. There was a statistically significant association between the relative amount of bacterial DNA in the pericardial fluid and the severity of CAD (p=0.035). CONCLUSIONS: Oral bacterial DNA was detectable in pericardial fluid and an association between the severity of CAD and the total amount of bacterial DNA in pericardial fluid was found, suggesting that this kind of measurement might be useful for clinical purposes.