Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Reliable information about the prevalence of hypertension in different world regions is essential to the development of national and international health policies for prevention and control of this condition. We aimed to pool data from different regions of the world to estimate the overall prevalence and absolute burden of hypertension in 2000, and to estimate the global burden in 2025. We searched the published literature from Jan 1, 1980, to Dec 31, 2002, using MEDLINE, supplemented by a manual search of bibliographies of retrieved articles. We included studies that reported sex-specific and age-specific prevalence of hypertension in representative population samples. All data were obtained independently by two investigators with a standardised protocol and data-collection form. Overall, 26.4% (95% CI 26.0-26.8%) of the adult population in 2000 had hypertension (26.6% of men [26.0-27.2%] and 26.1% of women [25.5-26.6%]), and 29.2% (28.8-29.7%) were projected to have this condition by 2025 (29.0% of men [28.6-29.4%] and 29.5% of women [29.1-29.9%]). The estimated total number of adults with hypertension in 2000 was 972 million (957-987 million); 333 million (329-336 million) in economically developed countries and 639 million (625-654 million) in economically developing countries. The number of adults with hypertension in 2025 was predicted to increase by about 60% to a total of 1.56 billion (1.54-1.58 billion). Hypertension is an important public-health challenge worldwide. Prevention, detection, treatment, and control of this condition should receive high priority.

The age-specific relevance of blood pressure to cause-specific mortality is best assessed by collaborative meta-analysis of individual participant data from the separate prospective studies. Information was obtained on each of one million adults with no previous vascular disease recorded at baseline in 61 prospective observational studies of blood pressure and mortality. During 12.7 million person-years at risk, there were about 56000 vascular deaths (12000 stroke, 34000 ischaemic heart disease [IHD], 10000 other vascular) and 66000 other deaths at ages 40-89 years. Meta-analyses, involving "time-dependent" correction for regression dilution, related mortality during each decade of age at death to the estimated usual blood pressure at the start of that decade. Within each decade of age at death, the proportional difference in the risk of vascular death associated with a given absolute difference in usual blood pressure is about the same down to at least 115 mm Hg usual systolic blood pressure (SBP) and 75 mm Hg usual diastolic blood pressure (DBP), below which there is little evidence. At ages 40-69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) is associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. All of these proportional differences in vascular mortality are about half as extreme at ages 80-89 years as at ages 40-49 years, but the annual absolute differences in risk are greater in old age. The age-specific associations are similar for men and women, and for cerebral haemorrhage and cerebral ischaemia. For predicting vascular mortality from a single blood pressure measurement, the average of SBP and DBP is slightly more informative than either alone, and pulse pressure is much less informative. Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.